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Sample records for placebo-controlled crossover study

  1. Gabapentin in traumatic nerve injury pain: A randomized, double-blind, placebo-controlled, cross-over, multi-center study

    DEFF Research Database (Denmark)

    Gordh, Torsten E; Stubhaug, Audun; Jensen, Troels S

    2008-01-01

    A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400mg/day. The study comprised a run...

  2. Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

    Directory of Open Access Journals (Sweden)

    Jenkins TM

    2012-07-01

    Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

  3. The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study.

    Science.gov (United States)

    Larsson, Pål Gunnar; Bakke, Kristin A; Bjørnæs, Helge; Heminghyt, Einar; Rytter, Elisif; Brager-Larsen, Line; Eriksson, Ann-Sofie

    2012-05-01

    Electric Status Epilepticus during Sleep (ESES) occurs in children with and without epilepsy. It may be related to disturbances as autism spectrum disorder, attention-deficit hyperactivity disorder and acquired aphasia (Landau-Kleffner syndrome). Antiepileptic drug (AED) treatment has been reported in small studies without placebo control. This study was designed to assess AED effect in a placebo-controlled double-blind cross-over study. Levetiracetam (LEV) was chosen based on clinical evidence. Eighteen patients fulfilled the inclusion criteria. The mean spike index at baseline was 56, falling to a mean of 37 at the end of the LEV treatment period. Assessed with a 2-way ANOVA, there is a significant treatment effect (pdouble-blind cross-over study for any AED in patients with ESES. The effect of LEV is comparable with its effect in treatment of epileptic seizures. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

    2013-12-01

    Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

  5. Caffeine improves endurance in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study

    DEFF Research Database (Denmark)

    Buchard Nørager, Charlotte; Jensen, Martin Bach; Madsen, Mogens Rørbæk

    2005-01-01

    This study investigated the effect of caffeine on physical performance in healthy citizens aged ≥70 yr. The randomized, double-blind, placebo-controlled, crossover study was conducted in 15 men and 15 women recruited by their general practitioner. Participants abstained from caffeine for 48 h...... and were randomized to receive one capsule of placebo and then caffeine (6 mg/kg) or caffeine and then placebo with 1 wk in between. One hour after intervention, we measured reaction and movement times, postural stability, walking speed, cycling at 65% of expected maximal heart rate, perceived effort...... during cycling, maximal isometric arm flexion strength, and endurance. Analysis was by intention to treat, and P Caffeine increased cycling endurance by 25% [95% confidence interval (CI): 13–38; P = 0.0001] and isometric arm flexion endurance by 54% (95% CI: 29–83; P...

  6. Escitalopram in painful polyneuropathy: A randomized, placebo-controlled, cross-over trial

    DEFF Research Database (Denmark)

    Otto, Marit; Bach, Flemming W; Jensen, Troels S

    2008-01-01

    Serotonin (5-HT) is involved in pain modulation via descending pathways in the central nervous system. The aim of this study was to test if escitalopram, a selective serotonin reuptake inhibitor (SSRI), would relieve pain in polyneuropathy. The study design was a randomized, double-blind, placebo......-controlled cross-over trial. The daily dose of escitalopram was 20mg once daily. During the two treatment periods of 5 weeks duration, patients rated pain relief (primary outcome variable) on a 6-point ordered nominal scale. Secondary outcome measures comprised total pain and different pain symptoms (touch...

  7. Caffeine counteracts impairments in task-oriented psychomotor performance induced by chlorpheniramine: a double-blind placebo-controlled crossover study.

    Science.gov (United States)

    Kim, Sung-Wan; Bae, Kyung-Yeol; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Kim, Jong-Keun; Kang, Gaeun; Yoon, Jin-Sang

    2013-01-01

    This study aimed to evaluate the effects of chlorpheniramine on psychomotor performance and the counteracting effects of caffeine on those sedative antihistamine actions. Sixteen healthy young men participated in this study. Using a double-blind placebo-controlled crossover design, each subject was administered one of the following conditions in a random order with a one-week interval: 'placebo-placebo', '4 mg of chlorpheniramine-placebo', 'placebo-200 mg of caffeine' or '4 mg of chlorpheniramine-200 mg of caffeine'. Before and after the treatments, psychomotor functions were assessed using a battery of tests. Additionally, subjective responses were assessed using a visual analogue scale (VAS). Psychomotor performance changed over time in different ways according to the combination of study medications. In the 'chlorpheniramine-placebo' condition, reaction times of the compensatory tracking task were significantly impaired compared with the other three conditions. In addition, the number of omission errors of the continuous performance test were significantly greater compared with the 'placebo-caffeine' condition. However, the response pattern of the 'chlorpheniramine-caffeine' condition was not significantly different from that of the 'placebo-placebo' condition. Changes of VAS for sleepiness were significantly greater in the 'chlorpheniramine-placebo' condition compared with the other three conditions. In conclusion, chlorpheniramine significantly increases subjective sleepiness and objectively impairs psychomotor performance. However, caffeine counteracts these sedative effects and psychomotor impairments.

  8. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study

    DEFF Research Database (Denmark)

    Hauge, Anne W; Asghar, Mohammed S; Schytz, Henrik W

    2009-01-01

    BACKGROUND: Migraine with aura is thought likely to be caused by cortical spreading depression (CSD). Tonabersat inhibits CSD, and we therefore investigated whether tonabersat has a preventive effect in migraine with aura. METHODS: In this randomised, double-blind, placebo-controlled crossover......, of whom 31 were included in the statistical analysis of efficacy. Median (IQR) attacks of aura were reduced from 3.2 (1.0-5.0) per 12 weeks on placebo to 1.0 (0-3.0) on tonabersat (p=0.01), whereas the other primary outcome measure, median migraine headache days with or without aura, was not significantly...... inhibitory effect on CSD. The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura. FUNDING: Minster Pharmaceuticals; Lundbeck Foundation....

  9. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia

    DEFF Research Database (Denmark)

    Volkmann, H; Nørregaard, J; Jacobsen, Søren

    1997-01-01

    The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial. There was no sign......The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial.......17) and slight improvement only on fatigue, quality of sleep, morning stiffness, and on the Fibromyalgia Impact Questionnaire for pain. No effect could be observed on isokinetic muscle strength, Zerrsen self-assessment questionnaire, and the face scale. No effect of SAMe in patients with FM was found...

  10. Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

    Directory of Open Access Journals (Sweden)

    Jay K Udani

    2013-01-01

    Full Text Available Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P<0.05. When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P<0.05. There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

  11. Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

    Science.gov (United States)

    Udani, Jay K

    2013-01-01

    Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35-65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

  12. Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication.

    Science.gov (United States)

    Momsen, A H; Jensen, M B; Norager, C B; Madsen, M R; Vestersgaard-Andersen, T; Lindholt, J S

    2010-10-01

    Intermittent claudication is a disabling symptom of peripheral arterial disease for which few medical treatments are available. This study investigated the effect of caffeine on physical capacity in patients with intermittent claudication. This randomized double-blind placebo-controlled crossover study included 88 patients recruited by surgeons from outpatient clinics. The participants abstained from caffeine for 48 h before each test and then received either a placebo or oral caffeine (6 mg/kg). After 75 min, pain-free and maximal walking distance on a treadmill, perceived pain, reaction times, postural stability, maximal isometric knee extension strength, submaximal knee extension endurance and cognitive function were measured. The analysis was by intention to treat. Caffeine increased the pain-free walking distance by 20.0 (95 per cent confidence interval 3.7 to 38.8) per cent (P = 0.014), maximal walking distance by 26.6 (12.1 to 43.0) per cent (P postural stability was reduced significantly, by 22.1 (11.7 to 33.4) per cent with eyes open (P < 0.001) and by 21.8 (7.6 to 37.8) per cent with eyes closed (P = 0.002). Neither reaction time nor cognition was affected. In patients with moderate intermittent claudication, caffeine increased walking distance, maximal strength and endurance, but affected balance adversely.

  13. Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study

    Science.gov (United States)

    Gunzler, Steven A.; Koudelka, Caroline; Carlson, Nichole E.; Pavel, Misha; Nutt, John G.

    2011-01-01

    Objective To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state. Design Randomized, double-blind, placebo-controlled, crossover clinical trial. Setting Academic movement disorders center. Patients Patients with Parkinson disease and motor fluctuations. Intervention Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (sub-threshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 μg/kg/h every 2 hours and 25 μg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 μg/kg/h every 2 hours and 100 μg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days. Main Outcome Measures Finger and foot tapping rates. Results There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P<.001) and trended toward increasing finger tapping compared with placebo infusions. Conclusions Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that pre-synaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease. PMID:18268187

  14. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study.

    Science.gov (United States)

    Libov, Igor; Miodownik, Chanoch; Bersudsky, Yuly; Dwolatzky, Tzvi; Lerner, Vladimir

    2007-07-01

    Piracetam is a potent antioxidant, a cerebral neuroprotector, a neuronal metabolic enhancer, and a brain integrative agent. More than 20 years ago, an intravenous preparation of piracetam demonstrated an improvement in the symptoms of tardive dyskinesia. The aim of our study was to reexamine the efficacy of piracetam in the treatment of tardive dyskinesia using an oral preparation. The study was conducted at the Be'er Sheva Mental Health Center from May 2003 to December 2004 and involved a 9-week, double-blind, crossover, placebo-controlled trial assessing 40 DSM-IV schizophrenic and schizo-affective patients with DSM-IV-TR tardive dyskinesia. All study subjects received their usual antipsychotic treatment. Initially, subjects were randomly assigned to receive 4 weeks of treatment with either piracetam (4800 mg/day) or placebo. Thereafter, following a washout period of 1 week, they entered the crossover phase of the study for a further 4 weeks. The change in score of the Extrapyramidal Symptom Rating Scale from baseline to the study endpoint was the primary outcome measure. The mean decrease in score from baseline to endpoint in the clinical global impression subscale in patients treated with piracetam was 1.1 points compared to 0.1 points in the placebo group (p = .004). The mean decrease in the tardive parkinsonism subscale was 8.7 points in patients treated with piracetam and 0.6 points in those on placebo (p = .001). The mean decrease in the tardive dyskinesia subscale was 3.0 points in the piracetam group in contrast to deterioration of condition in the placebo group by -0.2 points (p = .003). Piracetam appears to be effective in reducing symptoms of tardive dyskinesia. The specific mechanism by which piracetam may attenuate symptoms of tardive dyskinesia needs to be further evaluated. ClinicalTrials.gov identifier NCT00190008.

  15. Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

    Science.gov (United States)

    Taylor, Jerome H; Landeros-Weisenberger, Angeli; Coughlin, Catherine; Mulqueen, Jilian; Johnson, Jessica A; Gabriel, Daniel; Reed, Margot O; Jakubovski, Ewgeni; Bloch, Michael H

    2018-01-01

    Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

  16. Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Safarinejad, Mohammad Reza

    2005-01-01

    To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P Urtica dioica group (from 40.1 cc initially to 36.3 cc; P Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.

  17. The anticonvulsant levetiracetam for the treatment of pain in polyneuropathy: A randomized, placebo-controlled, cross-over trial

    DEFF Research Database (Denmark)

    Holbech, Jakob Vormstrup; Otto, Marit; Bach, Flemming W

    2011-01-01

    of this study was to test the analgesic effect of levetiracetam in painful polyneuropathy. METHODS: This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000mg/day versus placebo (6-week treatment periods). Patients with diagnosed polyneuropathy and symptoms for more than......-three patients were screened for participation and 39 patients entered the study. Thirty-five patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.29 versus placebo 2.28, p=0.979), total pain intensity (levetiracetam 5.5 versus placebo 5.3, p=0......Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam. OBJECTIVES: The aim...

  18. A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

    2016-01-01

    The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

  19. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

    Directory of Open Access Journals (Sweden)

    Matthias Huber

    Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

  20. Does granisetron eliminate the gag reflex? A crossover, double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Barenboim, Silvina Friedlander; Dvoyris, Vladislav; Kaufman, Eliezer

    2009-01-01

    Although gagging is a frequent problem that, when severe, can jeopardize the dental procedure, no single protocol is used to alleviate this phenomenon. Selective 5-HT3 antagonists, such as granisetron, may attenuate gagging. In this study, granisetron and placebo were administered intravenously, in a crossover, double-blind manner, to 25 healthy volunteers in 2 different sessions. Gagging levels were recorded before and after administration, as were BP, pulse, and O2 saturation. Recorded results were analyzed with the use of tests for nonparametric values (P = .05). A significant increase in the depth of swab insertion was noted after administration of both placebo and drug. The increase in drug effectiveness correlated with decreased body weight. The true efficacy of granisetron in gagger patients with this treatment protocol has yet to be fully established, although it has been theorized that an increased dosage of granisetron may have a better effect.

  1. Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study.

    Science.gov (United States)

    Thomson, M A; Jenkins, H R; Bisset, W M; Heuschkel, R; Kalra, D S; Green, M R; Wilson, D C; Geraint, M

    2007-11-01

    To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children. Randomised, double blind, placebo controlled crossover trial, with two 2-week treatment periods separated by a 2-week placebo washout. Six UK paediatric departments. 51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting > or =3 months), defined as or =25% of bowel movements with straining; > or =25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment. Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination. The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; pPEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (pPEG+E (41%) and placebo during treatment (45%). PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.

  2. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia

    DEFF Research Database (Denmark)

    Volkmann, H; Nørregaard, J; Jacobsen, Søren

    1997-01-01

    The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial. There was no sign......The objective of this study was to test the efficacy of intravenously administered S-adenosyl-L-methionine (SAMe) in patients with fibromyalgia (FM). Thirty-four out-patients with fibromyalgia symptoms received SAMe 600 mg i.v. or placebo daily for 10 days in a cross-over trial....... There was no significant difference in improvement in the primary outcome: tender point change between the two treatment groups. There was a tendency towards statistical significance in favour of SAMe on subjective perception of pain at rest (p = 0.08), pain on movement (p = 0.11), and overall well-being (p = 0.......17) and slight improvement only on fatigue, quality of sleep, morning stiffness, and on the Fibromyalgia Impact Questionnaire for pain. No effect could be observed on isokinetic muscle strength, Zerrsen self-assessment questionnaire, and the face scale. No effect of SAMe in patients with FM was found...

  3. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study

    OpenAIRE

    Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podg?rski, Tomasz

    2017-01-01

    The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, whil...

  4. Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Kondo, Sumio; Suzuki, Asahi; Kurokawa, Mihoko; Hasumi, Keiji

    2016-11-01

    Kale ( Brassica oleracea var. acephala ), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (C max ; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); Pkale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.

  5. BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

    Directory of Open Access Journals (Sweden)

    Singh Betsy B

    2009-06-01

    Full Text Available Abstract Background Delayed onset muscle soreness (DOMS is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein and muscle damage (creatine phosphokinase and myoglobin. Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

  6. BounceBack capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study.

    Science.gov (United States)

    Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

    2009-06-05

    Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack, to alleviate the severity of DOMS after standardized eccentric exercise. The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18-45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. In this controlled pilot study, intake of BounceBack capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). BounceBack capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results.

  7. BounceBack™ capsules for reduction of DOMS after eccentric exercise: a randomized, double-blind, placebo-controlled, crossover pilot study

    Science.gov (United States)

    Udani, Jay K; Singh, Betsy B; Singh, Vijay J; Sandoval, Elizabeth

    2009-01-01

    Background Delayed onset muscle soreness (DOMS) is muscle pain and discomfort experienced approximately one to three days after exercise. DOMS is thought to be a result of microscopic muscle fiber tears that occur more commonly after eccentric exercise rather than concentric exercise. This study sought to test the efficacy of a proprietary dietary supplement, BounceBack™, to alleviate the severity of DOMS after standardized eccentric exercise. Methods The study was a randomized, double-blind, placebo-controlled, crossover study. Ten healthy community-dwelling untrained subjects, ranging in age from 18–45 years, were enrolled. Mean differences within and between groups were assessed inferentially at each data collection time-point using t-tests for all outcome measures. Results In this controlled pilot study, intake of BounceBack™ capsules for 30 days resulted in a significant reduction in standardized measures of pain and tenderness post-eccentric exercise compared to the placebo group. There were trends towards reductions in plasma indicators of inflammation (high sensitivity C-reactive protein) and muscle damage (creatine phosphokinase and myoglobin). Conclusion BounceBack™ capsules were able to significantly reduce standardized measures of pain and tenderness at several post-eccentric exercise time points in comparison to placebo. The differences in the serological markers of DOMS, while not statistically significant, appear to support the clinical findings. The product appears to have a good safety profile and further study with a larger sample size is warranted based on the current results. PMID:19500355

  8. Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

    Science.gov (United States)

    Nakato, Rui; Manabe, Noriaki; Shimizu, Sayako; Hanayama, Kozo; Shiotani, Akiko; Hata, Jiro; Haruma, Ken

    2017-01-01

    The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD. © 2017 S. Karger AG, Basel.

  9. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome.

    Science.gov (United States)

    Peterson, P K; Pheley, A; Schroeppel, J; Schenck, C; Marshall, P; Kind, A; Haugland, J M; Lambrecht, L J; Swan, S; Goldsmith, S

    1998-04-27

    To provide a preliminary assessment of the efficacy and safety of fludrocortisone acetate treatment of chronic fatigue syndrome. A placebo-controlled, double-blind, random-allocation crossover trial of 6 weeks of fludrocortisone. An outpatient clinical trials unit. Twenty-five participants with chronic fatigue syndrome (mean age, 40 years; 19 [76%] women; mean duration of illness, 7.0 years) were recruited from a research and clinic registry. Five patients withdrew from the trial. All participants were scheduled to receive fludrocortisone acetate (0.1-0.2 mg) or a placebo for 6 weeks in each treatment. Self-administered questionnaires were completed at the beginning and end of each treatment arm that asked patients to rate the severity of their symptoms on a visual analogue scale. The Medical Outcomes Study 36-Item Short-Form Health Survey, a reaction time test, and a treadmill exercise test were used to assess functional status. Blood pressure, heart rate, and plasma norepinephrine levels were obtained at baseline. Blood pressure and heart rate were recorded at the end of the exercise test and monitored at all subsequent visits. At baseline, the study participants reported symptom severity greater than 5 for most symptoms, and all had evidence of marked functional impairments. No improvement was observed in the severity of any symptom or in any test of function for the 20 participants who completed both arms of the trial. Blood pressure and heart rate readings were unaffected by treatment, and plasma norepinephrine levels did not differ from those of a healthy control group. The incidence of adverse experiences was similar in the fludrocortisone and placebo arms of the trial. Low-dose fludrocortisone does not provide sufficient benefit to be evident in a preliminary blinded trial of unselected patients with chronic fatigue syndrome.

  10. Relationship of a Special Acidified Milk Protein Drink with Cognitive Performance: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Young Adults

    Directory of Open Access Journals (Sweden)

    Yoshie Saito

    2018-05-01

    Full Text Available A previous in vivo study with rats suggested that a special milk protein drink manufactured using an acidification procedure to suppress the aggregation of milk proteins was absorbed quickly after feeding. We performed a randomized, double-blind, placebo-controlled, repeated-measure crossover study to investigate the short-term effects on cognitive performance in 29 healthy young adult men after they consumed this drink in the morning. After an overnight fast, subjects were tested for performance in the Uchida–Kraepelin serial arithmetic test and the Stroop test as well as for subjective feeling, body temperature, and heart rate variability before and after consumption of either the acidified milk protein drink or an isoenergetic placebo drink. Subjects showed a significant improvement in performance in the Uchida–Kraepelin test, the primary outcome measured, when they consumed the acidified milk protein drink compared with the placebo control condition. In addition, consumption of the acidified milk protein drink, compared with the placebo control, was associated with increases in vagally-mediated heart rate variability indices which, from recent theoretical perspectives, may reflect a higher ability to modulate cognitive and behavioral processes. There was no significant difference in subjective feelings and body temperature between the test drink conditions. These data suggest that consumption of the acidified milk protein drink may improve cognitive performance, with possible involvement of physiological systems that regulate cognition and behavior.

  11. Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid - a double-blind placebo-controlled cross-over phase IIIB study.

    Science.gov (United States)

    Geisthoff, Urban W; Seyfert, Ulrich T; Kübler, Marcus; Bieg, Birgitt; Plinkert, Peter K; König, Jochem

    2014-09-01

    Epistaxis is the most frequent manifestation in hereditary hemorrhagic telangiectasia, in which no optimal treatment exists. It can lead to severe anemia and reduced quality of life. Positive effects of tranexamic acid, an antifibrinolytic drug, have been reported on epistaxis related to this disorder. We sought to evaluate the efficacy of treating nosebleeds in hereditary hemorrhagic telangiectasia with tranexamic acid. In a randomized, double-blind, placebo controlled, cross-over phase IIIB study, 1 gram of tranexamic acid or placebo was given orally 3 times daily for 3 months for a total of 6 months. 22 patients were included in the intention-to-treat analysis. Hemoglobin levels, the primary outcome measure, did not change significantly (p=0.33). The secondary outcome measure was epistaxis score and patients reported a statistically significant reduction in nosebleeds, equaling a clinically relevant 54% diminution (p=0.0031), as compared to the placebo period. No severe side effects were observed. Tranexamic acid reduces epistaxis in patients with hereditary hemorrhagic telangiectasia. (Clinical trial registration numbers: BfArM 141 CHC 9008-001 and ClinicalTrials.gov NCT01031992). Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Lactobacillus salivarius WB21--containing tablets for the treatment of oral malodor: a double-blind, randomized, placebo-controlled crossover trial.

    Science.gov (United States)

    Suzuki, Nao; Yoneda, Masahiro; Tanabe, Kazunari; Fujimoto, Akie; Iha, Kosaku; Seno, Kei; Yamada, Kazuhiko; Iwamoto, Tomoyuki; Masuo, Yosuke; Hirofuji, Takao

    2014-04-01

    This study evaluated the effect of probiotic intervention using lactobacilli on oral malodor. We conducted a 14-day, double-blind, placebo-controlled, randomized crossover trial of tablets containing Lactobacillus salivarius WB21 (2.0 × 10(9) colony-forming units per day) or placebo taken orally by patients with oral malodor. Organoleptic test scores significantly decreased in both the probiotic and placebo periods compared with the respective baseline scores (P < .001 and P = .002), and no difference was detected between periods. In contrast, the concentration of volatile sulfur compounds (VSCs) (P = .019) and the average probing pocket depth (P = .001) decreased significantly in the probiotic period compared with the placebo period. Bacterial quantitative analysis found significantly lower levels of ubiquitous bacteria (P = .003) and Fusobacterium nucleatum (P = .020) in the probiotic period. These results indicated that daily oral consumption of tablets containing probiotic lactobacilli could help to control oral malodor and malodor-related factors. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

    Science.gov (United States)

    Durkalec-Michalski, Krzysztof; Jeszka, Jan; Podgórski, Tomasz

    2017-07-14

    The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased ( p = 0.049) with a simultaneous reduction of fat mass ( p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold ( p athletes.

  14. No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Ludäscher, Petra; Schmahl, Christian; Feldmann, Robert E; Kleindienst, Nikolaus; Schneider, Miriam; Bohus, Martin

    2015-10-01

    Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder. © The Author(s) 2015.

  15. The Effect of Korean Red Ginseng on Sexual Function in Premenopausal Women: Placebo-Controlled, Double-Blind, Crossover Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ho Seok Chung

    2015-01-01

    Full Text Available This study investigated whether Korean red ginseng (KRG extracts could improve sexual function in premenopausal women. Forty-one premenopausal women participated in this placebo-controlled, double-blind, and crossover clinical study with administration of either three ginseng capsules (1 g per capsule or placebo daily. After 8 weeks of medication of KRG or placebo, medication was changed for the subjects to placebo or KRG after 2 weeks of washout period. The efficacy of KRG extracts was measured by using Female Sexual Function Index (FSFI. Results. Twenty-three women completed the study. Total FSFI scores increased after KRG treatment (from 20.13±2.87 to 23.98±4.10, p=0.015 and placebo treatment (from 20.06±2.64 to 23.78±3.28, p=0.003. However, this change was not significantly different between the two groups (p=0.702. KRG treatment significantly improved sexual desire, arousal, orgasm, and satisfaction domains; however, there was no treatment effect compared with placebo. There was a case of gastric discomfort after taking KRG extracts. Oral administration of KRG extracts improved sexual function in premenopausal women; however, there were no statistical significant changes compared to placebo. It implies that KRG extracts have a substantial placebo effect in premenopausal women with sexual dysfunction.

  16. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

    2007-12-01

    In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

  17. Effectiveness of low-dose doxycycline (LDD on clinical symptoms of Sjögren's Syndrome: a randomized, double-blind, placebo controlled cross-over study

    Directory of Open Access Journals (Sweden)

    Vuotila Tuija

    2007-12-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS. Low-dose doxycycline (LDD inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients. This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately. Results Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p Conclusion LDD may not be useful in reducing the primary SS symptoms.

  18. An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial.

    Science.gov (United States)

    Son, Mi Ju; Im, Hwi-Jin; Ku, Boncho; Lee, Jun-Hwan; Jung, So Young; Kim, Young-Eun; Lee, Sung Bae; Kim, Jun Young; Son, Chang-Gue

    2018-01-01

    Introduction: Gongjin-dan (GJD) is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans. Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted. Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration ( p = 0.25), but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels ( p = 0.14). Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07) and the Fatigue Severity Scale (FSS, p = 0.13) questionnaires. BFI and FSS scores in the first stage (before the crossover), however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05) after GJD treatment (relative to placebo). GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire ( p = 0.06), with a significant improvement specifically in the condition "Getting To Sleep" ( p = 0.02). Five participants experienced minor adverse

  19. An Herbal Drug, Gongjin-dan, Ameliorates Acute Fatigue Caused by Short-Term Sleep-Deprivation: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mi Ju Son

    2018-05-01

    Full Text Available Introduction:Gongjin-dan (GJD is an herbal drug commonly used in Korea and China to combat fatigue, but there are only few clinical studies on its effectiveness and experimental studies on its mechanism of action, and no randomized controlled trial of GJD on the efficacy and mechanism of action has been reported. Here, we performed an exploratory study to evaluate both questions regarding GJD use in humans.Methods: A randomized, double-blinded, placebo-controlled, crossover clinical trial was conducted in the Republic of Korea. Healthy male participants were recruited and randomly allocated to groups receiving GJD-placebo or placebo-GJD in sequence. Fatigue was artificially induced by sleep deprivation for 2 nights. The primary outcome was a change in serum cortisol level; levels of biomarkers for stress hormones as well as oxidative stress and immunologic factors were also assessed, and questionnaires on fatigue and sleep quality were conducted.Results: Twelve and 11 participants were assigned to the GJD-placebo and placebo-GJD groups, respectively. Of all 23 participants, depending on crossover design, we analyzed a total of 20 participants for GJD, and 21 for placebo. An increase in serum cortisol appeared to be attenuated by GJD administration (p = 0.25, but the effect was not statistically significant; a similar pattern was observed in salivary cortisol levels (p = 0.14. Overall, GJD showed a tendency to reduce fatigue according to the Brief Fatigue Inventory (BFI, p = 0.07 and the Fatigue Severity Scale (FSS, p = 0.13 questionnaires. BFI and FSS scores in the first stage (before the crossover, however, were significantly improved (BFI, p = 0.02; FSS, p = 0.05 after GJD treatment (relative to placebo. GJD also seemed to improve sleep quality as assessed by the Leeds Sleep Evaluation Questionnaire (p = 0.06, with a significant improvement specifically in the condition “Getting To Sleep” (p = 0.02. Five participants experienced minor

  20. Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a randomized placebo-controlled cross-over study using pharmacological fMRI.

    Science.gov (United States)

    Goudriaan, Anna E; Veltman, Dick J; van den Brink, Wim; Dom, Geert; Schmaal, Lianne

    2013-02-01

    Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation. Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain

  1. Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study

    International Nuclear Information System (INIS)

    Incrocci, Luca; Koper, Peter C.M.; Hop, Wim C.J.; Slob, A. Koos

    2001-01-01

    Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer

  2. Melatonin versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial

    Science.gov (United States)

    Wright, Barry; Sims, David; Smart, Siobhan; Alwazeer, Ahmed; Alderson-Day, Ben; Allgar, Victoria; Whitton, Clare; Tomlinson, Heather; Bennett, Sophie; Jardine, Jenni; McCaffrey, Nicola; Leyland, Charlotte; Jakeman, Christine; Miles, Jeremy

    2011-01-01

    Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant…

  3. Effect of oral administration of freshly pressed juice of Echinacea purpurea on the number of various subpopulations of B- and T-lymphocytes in healthy volunteers: results of a double-blind, placebo-controlled cross-over study

    DEFF Research Database (Denmark)

    Schwarz, Evelyn; Parlesak, Alexandr; Henneicke-von-Zeppelin, H. H.

    2005-01-01

    BACKGROUND: In a recent double-blind placebo-controlled crossover-study the "immune stimulatory" effects (activation of macrophages leading to enhanced phagocytosis and production of several cytokines) of Echinacea purpurea preparations (EPP) which were observed in vitro experiments and following...

  4. The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial.

    Science.gov (United States)

    Pakdaman, Michael N; Udani, Jay K; Molina, Jhanna Pamela; Shahani, Michael

    2016-05-20

    Lactose intolerance is a form of lactose maldigestion where individuals experience symptoms such as diarrhea, abdominal cramping, flatulence, vomiting and bowel sounds following lactose consumption. Lactobacillus acidophilus is a species of bacteria known for its sugar fermenting properties. Preclinical studies have found that Lactobacillus acidophilus supplementation may assist in breaking down lactose; however, no human clinical trials exist evaluating its efficacy in alleviating symptoms related to lactose intolerance. The aim of this randomized, double-blind, placebo-controlled, crossover study was to evaluate the effect of a proprietary strain of Lactobacillus acidophilus on relieving discomfort related to lactose intolerance. The study enrolled healthy volunteers between 18 and 75 years of age who complained of lactose intolerance. Screening visits included a lactose challenge visit to confirm eligibility based on a score of 10 or higher on subjective assessment of the following symptoms after lactose challenge: diarrhea, abdominal cramping, vomiting, audible bowel sounds, flatulence, and overall symptoms. Qualified subjects participated in a 2-arm crossover design, with each arm consisting of 4 weeks of intervention of either active or placebo product, with a 2-week washout period during crossover. The study product consisted of the DDS-1 strain of Lactobacillus acidophilus (Nebraska Cultures, Walnut Creek, California). The placebo was formulated from maltodextrin. Study participants were instructed to take the product once daily for 4 weeks. Data collected included subjective symptom scores related to lactose intolerance. Longitudinal comparison between the DDS-1 group and placebo group demonstrated statistically significant reductions in abdominal symptom scores during the 6-h Lactose Challenge at week 4 for diarrhea (p = 0.033), abdominal cramping (p = 0.012), vomiting (p = 0.0002), and overall symptom score (p = 0.037). No adverse

  5. Placebo controlled, crossover validation study of oral ibuprofen and topical hydrocortisone-21-acetate for a model of ultraviolet B radiation (UVR-induced pain and inflammation

    Directory of Open Access Journals (Sweden)

    Rother M

    2011-10-01

    Full Text Available Matthias Rother, Ilka RotherDepartment of Clinical Operations, X-pert Med GmbH, Graefelfing, GermanyBackground: Pain related to ultraviolet B radiation (UVR induced sunburn is an established, simple, acute pain model. One of the major criticisms is related to the potential dermal adverse events caused by the UVR exposure. This study tried to validate the model for oral and topical drugs and to define the minimum required UVR exposure.Methods: This subject- and observer-blinded, placebo-controlled, crossover study evaluated 600 mg oral ibuprofen (IB and topical hydrocortisone-21-acetate (HC twice daily (bid in 24 healthy volunteers. Treatment started immediately after irradiation and again at 12 hours, 24 hours, and 36 hours post-UVR. Assessment of hyperalgesia to heat and signs of inflammation (erythema, skin temperature for all areas was performed after UVR and again at 6, 12, 24, 36, and 48 hours. Subjects returned within 4–11 days to the study site for the second period of the study. As in the first period, subjects received HC at one side and topical placebo on the other side, but oral treatment was crossed-over.Results: The primary analysis failed to show the expected superiority of the IB-group vs the placebo group in period 1 of the study. Evaluating period 2 alone clearly showed the expected treatment effects of IB for erythema and heat pain threshold. The results were less pronounced for skin temperature. In contrast to IB vs oral placebo, there were no differences in treatment response between HC and topical placebo. UVR at all dosages induced profound erythema and reduction of heat pain threshold without causing blisters or other unexpected discomfort to the subjects. The changes were almost linear between 1 and 2 minimal erythema doses (MED, whereas the change from 2 to 3 MED was less pronounced.Conclusion: Use of 2 MED in upcoming studies seems to be reasonable to limit subjects' UVB exposure. The following procedural changes are

  6. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design

    Directory of Open Access Journals (Sweden)

    Gao Joseph

    2010-06-01

    Full Text Available Abstract Background Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX was assessed in adults (18-55 years with attention-deficit/hyperactivity disorder (ADHD using the simulated adult workplace environment. Methods After open-label dose optimization (4-week with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP total score (attempted+correct measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary and at each time point vs placebo (secondary, and ADHD Rating Scale IV (ADHD-RS-IV with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs, vital signs, and electrocardiograms. Results Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P P ≤ .0017 for each time point and change from predose (P P Conclusions LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours to last (14 hours postdose time point vs placebo in adults with ADHD. Trial Registration ClinicalTrials.gov Identifier: NCT00697515 Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX in Adults With Attention-Deficit Hyperactivity Disorder (ADHD http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1

  7. The effect of dipeptidyl peptidase 4 inhibition on gastric volume, satiation and enteroendocrine secretion in Type 2 diabetes: a double blind, placebo-controlled crossover study

    DEFF Research Database (Denmark)

    Vella, Adrian; Bock, Gerlies; Giesler, Paula D

    2008-01-01

    with type 2 diabetes. Methods: In a double blind, placebo-controlled crossover design, 14 subjects with type 2 diabetes received vildagliptin (50mg bid) or placebo for 10-days in random order separated by a 2-week washout. On day 7, fasting and post-meal gastric volumes were measured by a (99m...... ingested was recorded and symptoms similarly measured using VAS. Results: Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 + 21 vs. 247 + 19ml, p= 0.98) and fed (746 + 28 vs. 772 + 26ml, p= 0.54) gastric volumes, did not differ when subjects received vildagliptin or placebo. Treatment...... with vildagliptin did not alter the maximum tolerated volume of Ensure((R)) (1657 + 308 vs. 1389 + 197 ml, p= 0.15) or water compared to placebo (1371 + 141 vs. 1172 + 156 ml, p= 0.23). Vildagliptin was associated with decreased PYY concentrations 60 minutes after initiation of the meal (166 +/- 27 vs. 229 +/- 34...

  8. A randomized double-blind placebo-controlled crossover-style trial of buspirone in functional dysphagia and ineffective esophageal motility.

    Science.gov (United States)

    Aggarwal, Nitin; Thota, Prashanthi Nagavenkata; Lopez, Rocio; Gabbard, Scott

    2018-02-01

    Studies suggest that Ineffective Esophageal Motility (IEM) is the manometric correlate of Functional Dysphagia (FD). Currently, there is no accepted therapy for either condition. Buspirone is a serotonin modulating medication and has been shown to augment esophageal peristaltic amplitude in healthy volunteers. We aimed to determine if buspirone improves manometric parameters and symptoms in patients with overlapping IEM/FD. We performed a prospective, double-blind, placebo-controlled, crossover-style trial of 10 patients with IEM/FD. The study consisted of two 2-week treatment arms with a 2-week washout period. Outcomes measured at baseline, end of week 2, and week 6 include high resolution esophageal manometry (HREM), the Mayo Dysphagia Questionnaire-14 (MDQ-14), and the GERD-HRQL. The mean age of our 10 patients was 53 ± 9 years and 70% were female. After treatment with buspirone, 30% of patients had normalization of IEM on manometry; however, there was 30% normalization in the placebo group as well. Comparing buspirone to placebo, there was no statistically significant difference in the HREM parameters measured. There was also no statistically significant difference in symptom outcomes for buspirone compared to placebo. Of note, patients had a statistically significant decrease in the total GERD-HRQL total score when treated with placebo compared to baseline levels. Despite previous data demonstrating improved esophageal motility in healthy volunteers, our study shows no difference in terms of HREM parameters or symptom scores in IEM/FD patients treated with buspirone compared to placebo. Further research is necessary to identify novel agents for this condition. © 2017 John Wiley & Sons Ltd.

  9. A double-blind placebo-controlled cross-over clinical trial of DONepezil In Posterior cortical atrophy due to underlying Alzheimer's Disease: DONIPAD study.

    Science.gov (United States)

    Ridha, Basil H; Crutch, Sebastian; Cutler, Dawn; Frost, Christopher; Knight, William; Barker, Suzie; Epie, Norah; Warrington, Elizabeth K; Kukkastenvehmas, Riitta; Douglas, Jane; Rossor, Martin N

    2018-05-01

    The study investigated whether donepezil exerts symptomatic benefit in patients with posterior cortical atrophy (PCA), an atypical variant of Alzheimer's disease. A single-centre, double-blind, placebo-controlled, cross-over clinical trial was performed to assess the efficacy of donepezil in patients with PCA. Each patient received either donepezil (5 mg once daily in the first 6 weeks and 10 mg once daily in the second 6 weeks) or placebo for 12 weeks. After a 2-week washout period, each patient received the other treatment arm during the following 12 weeks followed by another 2-week washout period. The primary outcome was the Mini-Mental State Examination (MMSE) at 12 weeks. Secondary outcome measures were five neuropsychological tests reflecting parieto-occipital function. Intention-to-treat analysis was used. For each outcome measure, carry-over effects were first assessed. If present, then analysis was restricted to the first 12-week period. Otherwise, the standard approach to the analysis of a 2 × 2 cross-over trial was used. Eighteen patients (13 females) were recruited (mean age 61.6 years). There was a protocol violation in one patient, who subsequently withdrew from the study due to gastrointestinal side effects. There was statistically significant (p effect on MMSE. Therefore, the analysis of treatment effect on MMSE was restricted to the first 12-week period. Treatment effect at 6 weeks was statistically significant (difference = 2.5 in favour of donepezil, 95% CI 0.1 to 5.0, p effect at 12 weeks was close, but not statistically significant (difference = 2.0 in favour of donepezil, 95% CI -0.1 to 4.5, p > 0.05). There were no statistically significant treatment effects on any of the five neuropsychological tests, except for digit span at 12 weeks (higher by 0.5 digits in favour of placebo, 95% CI 0.1 to 0.9). Gastrointestinal side effects occurred most frequently, affecting 13/18 subjects (72%), and were the cause of study discontinuation in one

  10. A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults.

    Science.gov (United States)

    Schoenberg, Mike R; Rum, Ruba S; Osborn, Katie E; Werz, Mary Ann

    2017-09-01

    The cognitive and mood effects of levetiracetam (LEV) in older adults are not known. This study compared the cognitive and mood effects of LEV to placebo in healthy older adults. Cognitive, mood, and balance variables were compared between LEV and placebo using a randomized, double-blind, placebo-controlled crossover study with two 5-week treatment periods. Healthy volunteers (n = 20) aged 65-80 (mean age 72.4) received either LEV or placebo in which the LEV target dose was 1,000 mg/day. Volunteers, aged 65-80, were without epilepsy to limit potentially confounding the impact of seizures and/or underlying neuropathology on outcomes. LEV was initiated at 250 mg twice a day for 2 weeks, then increased to 500 mg twice a day for 2 weeks, and then tapered to 250 mg twice a day for 1 week. This was randomized with placebo for the two treatment arms. Measures included standardized neuropsychological, mood, and balance tests yielding 32 variables. Balance was assessed using subjective report (e.g., A-B neurotoxicity scale) and objective data (e.g., Berg Balance Scale). Average LEV serum concentration was 16.9 (standard deviation [SD} 7.7). Repeated-measures analysis of variance (ANOVA) found no differences between LEV and placebo phases for 29 (90.6%) of 32 variables including no change in balance. Performance on LEV was better than placebo on a visual memory (MCG Complex Figure Recall; p = 0.007) and two attention tests (Trail Making Test, Part A, p = 0.009; Stroop Interference, p = 0.004). There was a trend for greater irritability and fatigue (POMS Anger and Fatigue) during the LEV phase (p = 0.029, p = 0.035). Effect-size changes were generally small (Cohen d < 0.5). LEV was well tolerated in this elderly population in terms of cognition, mood, and balance. When anticonvulsant medication is indicated for older adults, LEV has pharmacokinetic advantages, and these data indicate no adverse impact on cognition or balance. Wiley Periodicals, Inc. © 2017 International

  11. Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

    Science.gov (United States)

    Kohsaka, Masako; Kanemura, Takashi; Taniguchi, Mitsutaka; Kuwahara, Hiroo; Mikami, Akira; Kamikawa, Kunihisa; Uno, Hideki; Ogawa, Atsushi; Murasaki, Mitsukuni; Sugita, Yoshiro

    2011-10-01

    The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

  12. Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial

    Directory of Open Access Journals (Sweden)

    Pouryaghoub Gholamreza

    2008-10-01

    Full Text Available Abstract Background Night work is associated with disturbed sleep and wakefulness, particularly in relation to the night shift. Circadian rhythm sleep disorders are characterized by complaints of insomnia and excessive daytime sleepiness that are primarily due to alterations in the internal circadian timing system or a misalignment between the timing of sleep and the 24-h social and physical environment. Methods We evaluated the effect of oral intake of 5 mg melatonin taken 30 minutes before night time sleep on insomnia parameters as well as subjective sleep onset latency, number of awakenings, and duration of sleep. A double-blind, randomized, placebo-controlled crossover study with periods of 1 night and washouts of 4 days comparing melatonin with placebo tablets was conducted. We tried to improve night-time sleep during recovery from night work. Participants were 86 shift-worker nurses aged 24 to 46 years. Each participant completed a questionnaire immediately after awakening. Results Sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time. No adverse effects of melatonin were noted during the treatment period. Conclusion Melatonin may be an effective treatment for shift workers with difficulty falling asleep.

  13. Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study.

    Science.gov (United States)

    Erlendson, Matthew J; D'Arcy, Nicole; Encisco, Ellen M; Yu, Jeffrey J; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J David; Chu, Larry F

    2017-01-01

    Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. At timepoint T = 0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N = 10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10 mg/70kg). At T = 165, 10 mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Comparison of average baseline OOWS scores with OOWS scores obtained 15 minutes after naloxone was significant (p = 0.0001). Scores from 15 minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5 ± 0.97; and palonosetron with hydroxyzine, 0.2 ± 0.1333. Pretreatment with palonosetron significantly reduced many signs of experimentally-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal.

  14. A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

    Science.gov (United States)

    Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

    2012-01-01

    Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

  15. The administration to Indonesians of monosodium L-glutamate in Indonesian foods: an assessment of adverse reactions in a randomized double-blind, crossover, placebo-controlled study.

    Science.gov (United States)

    Prawirohardjono, W; Dwiprahasto, I; Astuti, I; Hadiwandowo, S; Kristin, E; Muhammad, M; Kelly, M F

    2000-04-01

    Monosodium L-glutamate (MSG) has been suggested to cause postprandial symptoms after the ingestion of Chinese or oriental meals. Therefore, we examined whether such symptoms could be elicited in Indonesians ingesting levels of MSG typically found in Indonesian cuisine. Healthy volunteers (n = 52) were treated with capsules of placebo or MSG (1.5 and 3.0 g/person) as part of a standardized Indonesian breakfast. The study used a rigorous, randomized, double-blind, crossover design. The occurrence of symptoms after MSG ingestion did not differ from that after consumption of the placebo.

  16. Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM.

    Science.gov (United States)

    Puig, J G; Calvo, C; Luurila, O; Luurila, H; Sulosaari, S; Strandberg, A; Ghezzi, C

    2007-12-01

    This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated.

  17. Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism.

    Science.gov (United States)

    Chez, Michael; Lepage, Christopher; Parise, Carol; Dang-Chu, Ashley; Hankins, Andrea; Carroll, Michael

    2018-04-01

    The aim of this exploratory study was to assess the safety and clinical effects of autologous umbilical cord blood (AUCB) infusion in children with idiopathic autism spectrum disorder (ASD). Twenty-nine children 2 to 6 years of age with a confirmed diagnosis of ASD participated in this randomized, blinded, placebo-controlled, crossover trial. Participants were randomized to receive AUCB or placebo, evaluated at baseline, 12, and 24 weeks, received the opposite infusion, then re-evaluated at the same time points. Evaluations included assessments of safety, Expressive One Word Picture Vocabulary Test, 4th edition, Receptive One Word Picture Vocabulary Test, 4th edition, Clinical Global Impression, Stanford-Binet Fluid Reasoning and Knowledge, and the Vineland Adaptive Behavior and Socialization Subscales. Generalized linear models were used to assess the effects of the response variables at the 12- and 24-week time periods under each condition (AUCB, placebo). There were no serious adverse events. There were trends toward improvement, particularly in socialization, but there were no statistically significant differences for any endpoints. The results of this study suggest that autologous umbilical cord infusions are safe for children with ASD. Tightly controlled trials are necessary to further progress the study of AUCB for autism. Stem Cells Translational Medicine 2018;7:333-341. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  18. Antispasmodic/analgesic associations in primary dysmenorrhea double-blind crossover placebo-controlled clinical trial.

    Science.gov (United States)

    de los Santos, A R; Zmijanovich, R; Pérez Macri, S; Martí, M L; Di Girolamo, G

    2001-01-01

    We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods.

  19. A human model of inflammatory cardio-metabolic dysfunction; a double blind placebo-controlled crossover trial

    Directory of Open Access Journals (Sweden)

    Mehta Nehal N

    2012-06-01

    Full Text Available Abstract Background Chronic inflammation may contribute to insulin resistance (IR, metabolic syndrome and atherosclerosis although evidence of causality is lacking in humans. We hypothesized that very low-dose experimental endotoxemia would induce adipose tissue inflammation and systemic IR during a low-grade but asymptomatic inflammatory response and thus provide an experimental model for future tests of pharmacologic and genomic modulation of cardio-metabolic traits in humans. Methods Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8 were randomized in a double-masked, placebo-controlled, crossover study to separate 36-hour inpatient visits (placebo versus intravenous-LPS 0.6 ng/kg. We measured clinical symptoms via the McGill pain questionnaire and serial vital signs. Plasma and serum were collected for measurement of cytokines, C-reactive protein, insulin and glucose, serial whole blood & subcutaneous adipose tissue mRNA expression were measured by real-time PCR. HOMA-IR, a well-validated measure of IR was calculated to estimate insulin resistance, and frequently sampled intravenous glucose tolerance testing (FSIGTT was performed to confirm an insulin resistant state. We performed ANOVA and within subject ANOVA to understand the differences in cytokines, adipose tissue inflammation and IR before and after LPS or placebo. Results There was no significant difference between placebo and LPS in clinical responses of symptom scores, body temperature or heart rate. However, low-dose endotoxemia induced a rapid and transient 25-fold induction of plasma TNF-alpha and 100-fold increase in plasma IL-6 (Figure 1B (p p p = 0.01 increased with MCP-1 (peak 10-fold, F = 5.6, p p p p  Conclusions We present a low dose human endotoxemia model of inflammation which induces adipose tissue inflammation and systemic insulin resistance in the absence of overt clinical response. Such a model has the potential

  20. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.

    Science.gov (United States)

    Enseleit, Frank; Sudano, Isabella; Périat, Daniel; Winnik, Stephan; Wolfrum, Mathias; Flammer, Andreas J; Fröhlich, Georg M; Kaiser, Priska; Hirt, Astrid; Haile, Sarah R; Krasniqi, Nazmi; Matter, Christian M; Uhlenhut, Klaus; Högger, Petra; Neidhart, Michel; Lüscher, Thomas F; Ruschitzka, Frank; Noll, Georg

    2012-07-01

    Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F(2t)-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.

  1. Efficacy of topical Rose (Rosa damascena Mill.) oil for migraine headache: A randomized double-blinded placebo-controlled cross-over trial.

    Science.gov (United States)

    Niazi, Maria; Hashempur, Mohammad Hashem; Taghizadeh, Mohsen; Heydari, Mojtaba; Shariat, Abdolhamid

    2017-10-01

    To evaluate the effect of topical formulation of Rosa damascena Mill. (R. damascena) oil on migraine headache, applying syndrome diffrentiation model. Forty patients with migraine headache were randomly assigned to 2 groups of this double-blind, placebo-controlled cross-over trial. The patients were treated for the first 2 consecutive migraine headache attacks by topical R. damascena oil or placebo. Then, after one week of washout period, cross-over was done. Pain intensity of the patients' migraine headache was recorded at the beginnig and ten-sequence time schadule of attacks up to 24h. In addition, photophobia, phonophobia, and nausea and/or vomitting (N/V) of the patients were recorded as secondary outcomes. Finally, gathered data were analysed in a syndrome differentiation manner to assess the effect of R. damascena oil on Hot- and Cold-type migraine headache. Mean pain intensity of the patients' migraine headache in the different time-points after R. damascena oil or placebo use, was not significantly different. Additionally, regarding mean scores of N/V, photophobia, and phonophobia severity of the patients, no significant differences between the two groups were observed. Finally, applying syndrome differentiation model, the mean score of migraine headache pain intensity turned out to be significantly lower in patients with "hot" type migraine syndrome at in 30, 45, 60, 90, and 120min after R. damascena oil application compared to "cold" types (P values: 0.001, 0.001, <0.001, <0.001, and 0.02; respectively). It seems that syndrome differentiation can help in selection of patients who may benefit from the topical R. damascena oil in short-term relief of pain intensity in migraine headache. Further studies of longer follow-up and larger study population, however, are necessitated for more scientifically rigorous judgment on efficacy of R. damascena oil for patients with migraine headache. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

    Science.gov (United States)

    Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

    2017-05-01

    This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P 0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

  3. Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial.

    Science.gov (United States)

    Amen, Daniel G; Taylor, Derek V; Ojala, Kristine; Kaur, Jasleen; Willeumier, Kristen

    2013-01-01

    In a prior open trial of professional football players who displayed the effects of traumatic brain injury, the current reserach team reported significant improvements in clinical symptoms, neuropsychological testing and regional cerebral blood flow (rCBF) following the use of brain-directed nutrients (BDNs) and lifestyle interventions. The current study intended to determine whether supplementation with BDNs improved rCBF and neuropsychological function in healthy individuals. The current study was a randomized, doubleblind, placebo-controlled, crossover trial, which was a more rigorous reseach design than the prior study and did not include lifestyle interventions. Participants underwent evaluation and testing at the Amen Clinics, Inc, a private medical facility in Newport Beach, CA. Thirty healthy adult (15 male and 15 female) participants were recruited from the community though local advertising and met the requirements for eligibility into the study. Twenty-five individuals completed the study, with dropout due to events unrelated to the study itself. The participants were randomly assigned to a treatment order for intervention, either placebo or brain supplements first. The BDNs treatment was comprised of three supplements: fish oil; a high-potency, multiple vitamin/mineral supplement; and a brainenhancement supplement. The placebo treatment was two supplements comprised of rice flour to replace the multiple vitamin/mineral complex and the brain-enhancement supplement and one supplement made of other oils to replace the fish-oil mixture. After 2 mo of this first intervention, a crossover intervention occurred for a final 2 mo, in which participants formerly receiving BDNs received a placebo treatment and participants formerly treated with placebo received the BDNs treatment. Primary outcome measures included (1) an analysis of the changes in rCBF using SPECT and (2) an assessment of the differences in cognitive and emotional function using the Micro

  4. Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

    Science.gov (United States)

    Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

    2006-07-01

    Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

  5. Homeopathy for mental fatigue: lessons from a randomized, triple blind, placebo-controlled cross-over clinical trial

    Directory of Open Access Journals (Sweden)

    Dean Michael

    2012-10-01

    Full Text Available Abstract Background Difficulty in controlling attention can lead to mental fatigue in the healthy population. We identified one trial reporting a benefit in patients’ attention using a homeopathic formula preparation. One component of the preparation was potassium phosphate, widely available off the shelf as Kali phos 6x for cognitive problems. The aim of this exploratory trial was to assess the effectiveness of Kali phos 6x for attention problems associated with mental fatigue. Methods We recruited student and staff volunteers (University of York with self-reported mental fatigue, excluding any using homeopathy or prescribed stimulants, or with a diagnosis of chronic fatigue syndrome. In a triple blind, cross-over, placebo-controlled clinical trial, 86 volunteers were randomized to receive Kali phos 6x or identical placebo 10 minutes before taking a psychological test of attention (Stroop Colour-Word Test. One week later they were crossed over and took the other preparation before repeating the test. Results We found no evidence of a treatment effect in a comparison of Kali phos 6x with placebo (Kali phos minus placebo = −1.1 (95% CI −3.0 to 0.9, P = 0.3 Stroop score units, Cohen effect size = −0.17 even when allowing for a weak period effect with accuracy scores in the second period being higher than those in the first (P = 0.05. We observed a ceiling effect in the Stroop test which undermined our ability to interpret this result. Conclusions Kali phos 6x was not found to be effective in reducing mental fatigue. A ceiling effect in our primary outcome measure meant that we could not rule out a type II error. Thorough piloting of an adequate outcome measure could have led to an unequivocal result. Current Controlled Trials ISRCTN16521161

  6. An evaluation of the cognitive and mood effects of an energy shot over a 6h period in volunteers: a randomized, double-blind, placebo controlled, cross-over study.

    Science.gov (United States)

    Wesnes, Keith A; Barrett, Marilyn L; Udani, Jay K

    2013-08-01

    Energy drinks are widely available mostly containing glucose, and several have been demonstrated to improve alertness and cognitive function; these effects generally being identified 30-60min after administration. The present study assessed whether an energy shot without carbohydrates would affect major aspects of cognitive function and also mood in volunteers over a 6h time period. This randomized, double-blind, placebo-controlled,crossover study compared the acute effects of the energy shot with a matching placebo in 94 healthy volunteers. Cognitive function was assessed with a widely used set of automated tests of attention and memory. Mood was assessed with the Bond-Lader, Beck Anxiety Index, Beck Depression Index, Chalder Fatigue Scales (CFS), and the POMS. The volunteers were requested to limit their sleep to between 3 and 6h the night before each testing day. Compared to the placebo, the energy shot significantly improved 6 validated composite cognitive function measures from the CDR System as well as self-rated alertness; the benefits on 4 of the cognitive measures still remaining at 6h. The overall effect sizes of the performance improvements were in the small to medium range and thus notable in this field. In conclusion, an energy shot can significantly improve important aspects of cognitive function for up to 6h compared to placebo in partially sleep-deprived healthy volunteers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

    Directory of Open Access Journals (Sweden)

    David J. White

    2016-01-01

    Full Text Available l-theanine (γ-glutamylethylamide is an amino acid found primarily in the green tea plant. This study explored the effects of an l-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG. Thirty-four healthy adults aged 18–40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the l-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of l-theanine.

  8. Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    Li, Yanqing; Cheng, Lei; Chen, Xiaoning; Yang, Beibei; Wang, Dehui

    2015-01-01

    To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p 0.05), and no severe systematic reactions were observed. Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy.

  9. B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

    Science.gov (United States)

    Heinisch, B B; Vila, G; Resl, M; Riedl, M; Dieplinger, B; Mueller, T; Luger, A; Pacini, G; Clodi, M

    2012-05-01

    B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. ClinicalTrials.gov: NCT01324739 The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

  10. Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Taku Miyagawa

    Full Text Available UNLABELLED: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM sleep abnormalities. A genome-wide association study (GWAS identified a novel narcolepsy-related single nucleotide polymorphism (SNP, which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral L-carnitine for the treatment of narcolepsy, we performed a clinical trial administering L-carnitine (510 mg/day to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02. L-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. L-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 vitality and mental health subscales did not reach statistical significance between L-carnitine and placebo. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN UMIN000003760.

  11. Acute Garcinia mangostana (mangosteen) supplementation does not alleviate physical fatigue during exercise: a randomized, double-blind, placebo-controlled, crossover trial.

    Science.gov (United States)

    Chang, Chih-Wei; Huang, Tzu-Zung; Chang, Wen-Hsin; Tseng, Yi-Chun; Wu, Yu-Tse; Hsu, Mei-Chich

    2016-01-01

    The purple mangosteen (Garcinia mangostana), known as the "queen of fruit," is widely consumed and unique not only because of its outstanding appearance and flavor but also its remarkable and diverse pharmacological effects. The aim of the present study is to evaluate the effect of acute mangosteen supplementation on physical fatigue during exercise. A randomized, double-blind, placebo-controlled, crossover study was carried out by 12 healthy adults. The participants were randomly assigned to receive acute oral administration of either 250 mL of the mangosteen-based juice (supplementation treatment; 305 mg of α-mangostin and 278 mg of hydroxycitric acid) or a placebo (control treatment) 1 h before cycle ergometer exercise. Time to exhaustion, heart rate, Borg Rating of Perceived Exertion score, blood biochemical markers (namely ammonia, cortisol, creatine kinase, aspartate aminotransferase, alanine aminotransferase, glucose, and lactate), muscle dynamic stiffness, and Profile of Mood States (POMS) were evaluated and recorded. The results showed all parameters we examined were significantly altered by the exercise challenge, which demonstrated they directly reflected the condition of fatigue. However, there were no differences between the two treatments besides a positive impact on the POMS examination. The occurrence of physical fatigue depends on multiple underlying mechanisms. We concluded that acute mangosteen supplementation had no impact on alleviating physical fatigue during exercise.

  12. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study

    Directory of Open Access Journals (Sweden)

    Ravn P

    2013-01-01

    Full Text Available Pernille Ravn,1 Erik L Secher,2 Ulrik Skram,3 Trine Therkildsen,1 Lona L Christrup,1 Mads U Werner41Department of Drug Design and Pharmacology, University of Copenhagen, 2Department of Anesthesiology, Juliane Marie Center, Rigshospitalet, Copenhagen University Hospitals, 3Department of Intensive Care, Gentofte Hospital, Copenhagen University Hospitals, 4Multidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, DenmarkPurpose: Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than µ-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation.Subjects and methods: Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg, buprenorphine (0.3/0.6 mg, or placebo (normal saline were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2, and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist.Results: For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia

  13. A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Fuglsang, S.; Madsen, Jan Lysgård

    2008-01-01

    emptying, small intestinal transit and colonic transit of a radiolabelled, 1600-kJ mixed liquid and solid meal ingested on day 2. RESULTS: Aprepitant did not change gastric retention at 15 min, gastric half emptying time, gastric mean transit time, time to small intestinal transit of 10%, small intestinal...... in healthy humans. METHODS: Twelve healthy volunteers participated in a crossover, double-blind study. In random order, each volunteer had a 125-mg capsule of aprepitant or placebo on day 1 followed by an 80-mg capsule of aprepitant or placebo on days 2-5. Gamma camera imaging was used to measure gastric...

  14. Adjunctive treatment with lodenafil carbonate for erectile dysfunction in outpatients with schizophrenia and spectrum: a randomized, double-blind, crossover, placebo-controlled trial.

    Science.gov (United States)

    Nunes, Luciana Vargas Alves; Lacaz, Fernando Sargo; Bressan, Rodrigo Affonseca; Nunes, Sandra Odebrecht Vargas Alves; Mari, Jair de Jesus

    2013-04-01

    INTRODUCTION.: Evidence is accumulating to support the presence of erectile dysfunction in patients with schizophrenia. This dysregulation may be amenable to therapeutic intervention to improve adherence and quality of life of patients who suffer from schizophrenia and schizoaffective disorders. AIM.: We aimed to evaluate the use of adjunctive medication lodenafil for the treatment of erectile dysfunction in outpatients with schizophrenia and spectrum. METHODS.: The design was a randomized, double-blind, crossover, placebo-controlled trial with lodenafil and it was carried at the Schizophrenia Outpatients Program. MAIN OUTCOME MEASURES.: The measures used to assess sexual dysfunction were Arizona Sexual Experiences Scale (ASEX) and International Index of Erectile Function (IIEF). The Positive and Negative Syndrome Scale (PANSS) and the Quality of Life Scale (QLS) were also used. The measures included the levels of prolactin, estradiol, luteinizing hormone, sex hormone-binding globulin, free testosterone, and total testosterone at baseline and end point. Lodenafil and placebo pills were used by the patients for 16 weeks. RESULTS.: Fifty male outpatients fulfilled the criteria and 94% of the participants completed the study. Lodenafil and placebo produced improvement in ASEX, IIEF scale, PANSS, and QLS, and there was no statistical difference between lodenafil and placebo groups in all sexual domains in the results of PANSS and QLS and in the results of hormone levels. CONCLUSION.: These results indicate that both lodenafil and placebo were effective in the treatment of erectile dysfunction for schizophrenia. Placebo effect is very important in patients with schizophrenia and this study showed the importance of discussing sexuality and trying to treat these patients. Further studies designed to test treatments of erectile dysfunction in patients who suffer from schizophrenia are necessary. © 2013 International Society for Sexual Medicine.

  15. Efficacy of omeprazole on cough, pulmonary function and quality of life of patients with sulfur mustard lung injury: A placebo-control, cross-over clinical trial study

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Emami

    2014-01-01

    Full Text Available Background: Gastro-esophageal reflux disease (GERD is prevalent and related to more severe disease in patients with respiratory problems. We evaluated the effects of antireflux therapy in warfare victims of exposure to Mustard gas with chronic cough. Materials and Methods: This randomized, double-blind, placebo-controlled, cross-over study was conducted on 45 cases of sulfur mustard injury with chronic cough (≥8 weeks and GERD. Patients were randomized into two groups, receiving either 20 mg twice daily omeprazole-placebo (OP or matching placebo (placebo-omeprazole [PO] for 4 months, followed by a 1-month washout period and the alternative treatment for 4 months. Assessments included GERD and cough, quality of life, and pulmonary function using spirometry. Leicester Cough Questionnaire and SF-36 were used for measuring quality of life. Results: Patients in the OP group experienced a more decrease than those in the PO group in severity of Leicester cough scores during the first 4-month of trial. After crossing the groups, the OP group experienced an increase (P = 0.036 and the PO group experienced a nonsignificant decrease (P = 0.104 in the severity of scores. The OP group also experienced improvement in GERD symptoms and quality of life at the end of the trial, but changes in the PO group was not significant. There was no significant change in respiratory function indices in any groups. Conclusion: Long-term treatment with high-dose omeprazole improved GERD as well as cough, and quality of life, but not changed respiratory function indices in sulfur mustard injured cases with respiratory symptoms.

  16. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Vance L Albaugh

    Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

  17. Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic: a randomised, double-blind, placebo-controlled, cross-over, human intervention study.

    Science.gov (United States)

    Healey, Genelle; Murphy, Rinki; Butts, Christine; Brough, Louise; Whelan, Kevin; Coad, Jane

    2018-01-01

    Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti® Synergy 1; 16 g/d) or placebo (Glucidex® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium (P=0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium (Pgut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.

  18. Effect of a fermented dietary supplement containing chromium and zinc on metabolic control in patients with type 2 diabetes: a randomized, placebo-controlled, double-blind cross-over study

    Directory of Open Access Journals (Sweden)

    Yu-Mi Lee

    2016-06-01

    Full Text Available Background: For the increasing development of type 2 diabetes dietary habits play an important role. In this regard, dietary supplements are of growing interest to influence the progression of this disease. Objective: The aim of this study was to investigate the effect of a cascade-fermented dietary supplement based on fruits, nuts, and vegetables fortified with chromium and zinc on metabolic control in patients with type 2 diabetes mellitus. Methods: This was a randomized, placebo-controlled, double-blind, intervention study under free-living conditions using a cross-over design. Thirty-six patients with type 2 diabetes mellitus were enrolled and randomized either to receive a cascade-fermented dietary supplement enriched with chromium (100 µg/d and zinc (15 mg/d or a placebo similar in taste but without supplements, over a period of 12 weeks. After a wash-out period of 12 weeks, the patients received the other test product. The main outcome variable was the levels of glycated hemoglobin (HbA1c. Other outcome variables were fasting blood glucose, fructosamine, and lipid parameters. Results: Thirty-one patients completed the study. HbA1c showed no relevant changes during both treatment periods, nor was there a relevant difference between the two treatments (HbA1c: p=0.48. The same results were found for fructosamine and fasting glucose (fructosamine: p=0.9; fasting glucose: p=0.31. In addition, there was no effect on lipid metabolism. Conclusion: This intervention study does not provide evidence that a cascade-fermented plant-based dietary supplement enriched with a combination of chromium and zinc improves glucose metabolism in patients with type 2 diabetes mellitus under free-living conditions.

  19. In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial.

    Science.gov (United States)

    Brown, S G A; Haas, M A; Black, J A; Parameswaran, A; Woods, G M; Heddle, R J

    2004-05-01

    In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. During a double-blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT the following venom-specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre-incubation with IL-3. None of the tests evaluated appear to be reliable markers of successful VIT.

  20. Immediate effects of kinesiotaping on quadriceps muscle strength: a single-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    Vercelli, Stefano; Sartorio, Francesco; Foti, Calogero; Colletto, Lorenzo; Virton, Domenico; Ronconi, Gianpaolo; Ferriero, Giorgio

    2012-07-01

    To investigate the immediate effects on maximal muscle strength of kinesiotaping (KT) applied to the dominant quadriceps of healthy subjects. Single-blind, placebo-controlled crossover trial. "Salvatore Maugeri" Foundation. With ethical approval and informed consent, a convenience sample of 36 healthy volunteers were recruited. Two subjects did not complete the sessions and were excluded from the analysis. Subjects were tested across 3 different sessions, randomly receiving 2 experimental KT conditions applied with the aim of enhancing and inhibiting muscle strength and a sham KT application. Quadriceps muscle strength was measured by means of an isokinetic maximal test performed at 60 and 180 degrees per second. Two secondary outcome measures were performed: the single-leg triple hop for distance to measure limb performance and the Global Rating of Change Scale (GRCS) to calculate agreement between KT application and subjective perception of strength. Compared with baseline, none of the 3 taping conditions showed a significant change in muscle strength and performance (all P > 0.05). Effect size was very low under all conditions (≤0.08). Very few subjects showed an individual change greater than the minimal detectable change. Global Rating of Change Scale scores demonstrated low to moderate agreement with the type of KT applied, but some placebo effects were reported independently of condition. Our findings indicated no significant effect in the maximal quadriceps strength immediately after the application of inhibition, facilitation, or sham KT. These results do not support the use of KT applied in this way to change maximal muscle strength in healthy people.

  1. Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

    Science.gov (United States)

    Dietrichson, P; Espen, E

    1981-08-01

    Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors.

  2. Suicide risk in placebo-controlled studies of major depression

    NARCIS (Netherlands)

    Storosum, J. G.; van Zwieten, B. J.; van den Brink, W.; Gersons, B. P.; Broekmans, A. W.

    2001-01-01

    The purpose of this study was to determine if fear of an increased risk of attempted suicide in placebo groups participating in placebo-controlled studies is an argument against the performance of placebo-controlled trials in studies of major depression. All short-term and long-term,

  3. Antihyperalgesic efficacy of 5% lidocaine medicated plaster in capsaicin and sunburn pain models--two randomized, double-blinded, placebo-controlled crossover trials in healthy volunteers.

    Science.gov (United States)

    Gustorff, Burkhard; Hauer, David; Thaler, Johannes; Seis, Astrid; Draxler, Julia

    2011-12-01

    The aim of this research is to analyze analgesic efficacy of the 5% lidocaine medicated plaster in two randomized, double-blinded, placebo-controlled, crossover studies in 16 healthy volunteers using capsaicin and sunburn pain models. Lidocaine and placebo plasters were simultaneously applied to forearms and thighs at contralateral body sites for three alternating 12-h plaster-on/plaster-off periods. Between the second and third plaster-on period, 4.2-cm circular spots on both pretreated thighs were irradiated with three times the individual minimal erythema dose of UVB light. After the last plaster-on period, 20 μl of 0.1% capsaicin was injected intradermally into both forearms. The study was repeated using a single 12-h plaster application. The area of pinprick hyperalgesia was diminished by 53% (p sunburn model; the intensity of mechanical hyperalgesia to rigid filaments (8 - 512 mN) was reduced in both models. Cold pain perception threshold was reduced (19.7°C ± 8.0 vs 21.8°C ± 6.8 for placebo, p sunburn). Similar effects were observed in the 12-h exposure study. No effect was seen on capsaicin-induced spontaneous pain and flare size, or blood flow in the sunburn area, and heat hyperalgesia in either study. Lidocaine plaster effectively treats mechanical hyperalgesia and cold pain.

  4. Sodium valproate in the treatment of aggressive behavior in patients with dementia--a randomized placebo controlled clinical trial

    NARCIS (Netherlands)

    Sival, Rob C.; Haffmans, P. M. Judith; Jansen, Paul A. F.; Duursma, Sijmen A.; Eikelenboom, Piet

    2002-01-01

    OBJECTIVES: The efficacy and tolerability of sodium valproate 2 x 240 mg compared to placebo were investigated in aggressive behavior in dementia. DESIGN: A randomized, placebo controlled, double-blind cross-over design. The trial included a baseline period (one week); a placebo period (three

  5. A randomized double-blind, placebo-controlled, cross-over trial (Vestparoxy) of the treatment of vestibular paroxysmia with oxcarbazepine.

    Science.gov (United States)

    Bayer, Otmar; Brémová, Tatiana; Strupp, Michael; Hüfner, Katharina

    2018-02-01

    Vestibular paroxysmia (VP) is characterized by short, often oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes provoked by turning the head. Despite the description of the disease almost 40 years ago (first termed "disabling positional vertigo"), no controlled treatment trial has been published to date. The Vestparoxy trial was designed as a randomized, placebo-controlled, double-blind cross-over trial to examine the therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable VP. Patients were recruited from August 2005 to December 2011 in the outpatient Dizziness Unit of the Department of Neurology of the Munich University Hospital, and randomized to receive OXA (first week: 300 mg once per day, second week: 300 mg b.i.d., third week: 300 mg t.i.d. until the end of the third month), followed by placebo or vice versa with a 1-month wash-out period in between. The primary endpoint was the number of days with one or more attacks. Secondary endpoints were the number of attacks during the observed days, and the median (for each day) duration of attacks. All these endpoints were assessed using standardized diaries collected at the end of each treatment phase. Forty-three patients were randomized, 18 patients provided usable data (2525 patient days) for at least one treatment phase and were included in the main (intention-to-treat) analysis. The most common reasons for discontinuation documented were adverse events. The risk of experiencing a day with at least one attack was 0.41 under OXA, and 0.62 under placebo treatment, yielding a relative risk of 0.67 (95% CI 0.47-0.95, p = 0.025). The number of attacks during the observed days ratio was 0.53 (95% CI 0.42-0.68, p effects.

  6. Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Anton, Stephen D; Shuster, Jonathan; Leeuwenburgh, Christiaan

    2011-11-01

    Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia-derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. ClinicalTrials.gov (Identifier: NCT01238887).

  7. [Extracorporeal shockwave therapy (ESWT) as therapeutic option in supraspinatus tendon syndrome? One year results of a placebo controlled study].

    Science.gov (United States)

    Schmitt, J; Tosch, A; Hünerkopf, M; Haake, M

    2002-07-01

    Extracorporeal shock wave therapy (ESWT) is seen as a therapeutic option in the treatment of chronic supraspinatus tendinitis by some authors. To test whether ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33 mJ/mm2 is clinically superior to a sham ESWT treatment, a prospective, randomized, single-blinded, placebo-controlled study with an independent observer was performed. Forty patients were treated either by verum ESWT or sham ESWT under local anesthesia. Target criteria were the age-corrected Constant score, pain at rest and during activity on a visual analogue scale, and subjective improvement. Patients who reported no subjective improvement after 12 weeks were deblinded and received verum ESWT if they had belonged to the placebo group (partial crossover). The results of the verum group lie within the range of results for ESWT published by other authors. Patients in the placebo group with local anesthetic showed equally good results. At 12 weeks, and 1 year after intervention, no difference could be found between the verum and placebo groups regarding Constant score, pain, shoulder function, or subjective improvement. The nonresponders to the placebo ESWT continued to show no improvement after receiving verum ESWT. This contradicts a specific ESWT effect. Based on the results of this placebo-controlled study, ESWT appears to have no clinically relevant effect on supraspinatus tendinitis. The study underlines the importance of a control group in evaluating new treatment methods for diseases with unknown natural history.

  8. No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

    Science.gov (United States)

    Linares, Ila M P; Guimaraes, Francisco S; Eckeli, Alan; Crippa, Ana C S; Zuardi, Antonio W; Souza, Jose D S; Hallak, Jaime E; Crippa, José A S

    2018-01-01

    Cannabidiol (CBD) is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design. Twenty-seven healthy volunteers that fulfilled the eligibility criteria were selected and allocated to receive either CBD (300 mg) or placebo in the first night in a double-blind randomized design (one volunteer withdrew from the study). In the second night, the same procedure was performed using the substance that had not been administered in the previous occasion. CBD or placebo were administered 30 min before the start of polysomnography recordings that lasted 8 h. Cognitive and subjective measures were performed immediately after polysomnography to assess possible residual effects of CBD. The drug did not induce any significant effect ( p > 0.05). Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as in clinical trials with larger samples and chronic use of different doses of CBD. Such studies are desirable and opportune.

  9. No Acute Effects of Cannabidiol on the Sleep-Wake Cycle of Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

    Directory of Open Access Journals (Sweden)

    Ila M. P. Linares

    2018-04-01

    Full Text Available Cannabidiol (CBD is a component of Cannabis sativa that has a broad spectrum of potential therapeutic effects in neuropsychiatric and other disorders. However, few studies have investigated the possible interference of CBD on the sleep-wake cycle. The aim of the present study was to evaluate the effect of a clinically anxiolytic dose of CBD on the sleep-wake cycle of healthy subjects in a crossover, double-blind design. Twenty-seven healthy volunteers that fulfilled the eligibility criteria were selected and allocated to receive either CBD (300 mg or placebo in the first night in a double-blind randomized design (one volunteer withdrew from the study. In the second night, the same procedure was performed using the substance that had not been administered in the previous occasion. CBD or placebo were administered 30 min before the start of polysomnography recordings that lasted 8 h. Cognitive and subjective measures were performed immediately after polysomnography to assess possible residual effects of CBD. The drug did not induce any significant effect (p > 0.05. Different from anxiolytic and antidepressant drugs such as benzodiazepines and selective serotonin reuptake inhibitors, acute administration of an anxiolytic dose of CBD does not seem to interfere with the sleep cycle of healthy volunteers. The present findings support the proposal that CBD do not alter normal sleep architecture. Future studies should address the effects of CBD on the sleep-wake cycle of patient populations as well as in clinical trials with larger samples and chronic use of different doses of CBD. Such studies are desirable and opportune.

  10. The effect of Neuragen PN® on Neuropathic pain: A randomized, double blind, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Li Li

    2010-05-01

    Full Text Available Abstract Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p ® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0% subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601

  11. Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

    Science.gov (United States)

    Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio

    2012-06-01

    Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

  12. Orange Pomace Improves Postprandial Glycemic Responses: An Acute, Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Overweight Men

    Directory of Open Access Journals (Sweden)

    C.-Y. Oliver Chen

    2017-02-01

    Full Text Available Orange pomace (OP, a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-controlled, double blind, crossover trial with 34 overweight men who consumed either a 255 g placebo (PLA, a low (35% OP (LOP, or a high (77% (HOP dose OP beverage with breakfast. Blood was collected at 0, 10, 20, 30, and 45 min and at 1, 1.5, 2, 3, 4, 5, 5.5, 6, 6.5, 7, and 8 h. Lunch was consumed after the 5.5-h blood draw. OP delayed the time (Tmax1 to the maximum concentration (Cmax1 of serum glucose during the 2-h period post breakfast by ≥36% from 33 (PLA to 45 (HOP and 47 (LOP min (p = 0.055 and 0.013, respectively. OP decreased post-breakfast insulin Cmax1 by ≥10% and LOP delayed the Tmax1 by 14 min, compared to PLA at 46 min (p ≤ 0.05. HOP reduced the first 2-h insulin area under concentration time curve (AUC by 23% compared to PLA. Thus, OP diminishes postprandial glycemic responses to a high carbohydrate/fat breakfast and the second meal in overweight men.

  13. Chronic Effects of a Wild Green Oat Extract Supplementation on Cognitive Performance in Older Adults: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

    Directory of Open Access Journals (Sweden)

    Narelle M. Berry

    2012-05-01

    Full Text Available Background and aim: Preliminary evaluation of a wild green oat extract (WGOE (Neuravena® ELFA®955, Frutarom, Switzerland revealed an acute cognitive benefit of supplementation. This study investigated whether regular daily WGOE supplementation would result in sustained cognitive improvements. Method: A 12-week randomised, double-blind, placebo-controlled cross-over trial of WGOE supplementation (1500 mg/day versus placebo was undertaken in 37 healthy adults aged 67 ± 0.8 years (mean ± SEM. Cognitive assessments included the Stroop colour-word test, letter cancellation, the rule-shift task, a computerised multi-tasking test battery and the trail-making task. All assessments were conducted in Week 12 and repeated in Week 24 whilst subjects were fasted and at least 18 h after taking the last dose of supplement. Result: Chronic WGOE supplementation did not affect any measures of cognition. Conclusion: It appears that the cognitive benefit of acute WGOE supplementation does not persist with chronic treatment in older adults with normal cognition. It remains to be seen whether sustained effects of WGOE supplementation may be more evident in those with mild cognitive impairment.

  14. Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

    OpenAIRE

    Quintana, D S; Westlye, L T; Hope, S; N?rland, T; Elvs?shagen, T; D?rum, E; Rustan, ?; Valstad, M; Rezvaya, L; Lishaugen, H; Stens?nes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G

    2017-01-01

    The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin?s dose?response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequ...

  15. A randomized, double-blind, crossover, placebo-controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes.

    Science.gov (United States)

    Stirban, A; Pop, A; Tschoepe, D

    2013-10-01

    In a pilot study we suggested that benfotiamine, a thiamine prodrug, prevents postprandial endothelial dysfunction in people with Type 2 diabetes mellitus. The aim of this study was to test these effects in a larger population. In a double-blind, placebo-controlled, randomized, crossover study, 31 people with Type 2 diabetes received 900 mg/day benfotiamine or a placebo for 6 weeks (with a washout period of 6 weeks between). At the end of each treatment period, macrovascular and microvascular function were assessed, together with variables of autonomic nervous function in a fasting state, as well as 2, 4 and 6 h following a heated, mixed test meal. Participants had an impaired baseline flow-mediated dilatation (2.63 ± 2.49%). Compared with the fasting state, neither variable changed postprandially following the placebo treatment. The 6 weeks' treatment with high doses of benfotiamine did not alter this pattern, either in the fasting state or postprandially. Among a subgroup of patients with the highest flow-mediated dilatation, following placebo treatment there was a significant postprandial flow-mediated dilatation decrease, while this effect was attenuated by benfotiamine pretreatment. In people with Type 2 diabetes and markedly impaired fasting flow-mediated dilatation, a mixed test meal does not further deteriorate flow-mediated dilatation or variables of microvascular or autonomic nervous function. Because no significant deterioration of postprandial flow-mediated dilatation, microvascular or autonomic nervous function tests occurred after placebo treatment, a prevention of the postprandial deterioration of these variables with benfotiamine was not feasible. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  16. Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study.

    Directory of Open Access Journals (Sweden)

    Doriana Landi

    Full Text Available Flu-like syndrome (FLS is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS treated with interferon beta (IFNβ. FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6 in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS.We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2 first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS] after 4 weeks of treatment within each sequence.Forty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference -0.15; 95% confidence interval: from -0.74 to 0.44; p = 0.6029. The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile.The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFN

  17. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    International Nuclear Information System (INIS)

    Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

    2014-01-01

    Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

  18. Melatonin improves sleep in children with epilepsy: a randomized, double-blind, crossover study.

    Science.gov (United States)

    Jain, Sejal V; Horn, Paul S; Simakajornboon, Narong; Beebe, Dean W; Holland, Katherine; Byars, Anna W; Glauser, Tracy A

    2015-05-01

    Insomnia, especially maintenance insomnia, is widely prevalent in epilepsy. Although melatonin is commonly used, limited data address its efficacy. We performed a randomized, double-blind, placebo-controlled, crossover study to identify the effects of melatonin on sleep and seizure control in children with epilepsy. Eleven prepubertal, developmentally normal children aged 6-11 years with epilepsy were randomized by a software algorithm to receive placebo or a 9-mg sustained release (SR) melatonin formulation for four weeks, followed by a one-week washout and a four-week crossover condition. The pharmacy performed blinding; patients, parents, and study staff other than a statistician were blinded. The primary outcomes were sleep onset latency and wakefulness after sleep onset (WASO) measured on polysomnography. The secondary outcomes included seizure frequency, epileptiform spike density per hour of sleep on electroencephalogram (EEG), and reaction time (RT) measures on psychomotor vigilance task (PVT). Statistical tests appropriate for crossover designs were used for the analysis. Data were analyzed from 10 subjects who completed the study. Melatonin decreased sleep latency (mean difference, MD, of 11.4 min and p = 0.02) and WASO (MD of 22 min and p = 0.04) as compared to placebo. No worsening of spike density or seizure frequency was seen. Additionally, slow-wave sleep duration and rapid eye movement (REM) latency were increased with melatonin and REM sleep duration was decreased. These changes were statistically significant. Worsening of headache was noted in one subject with migraine on melatonin. SR melatonin resulted in statistically significant decreases in sleep latency and WASO. No clear effects on seizures were observed, but the study was too small to allow any conclusions to be drawn in this regard. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-controlled, crossover trial.

    Science.gov (United States)

    Wolz, Martin; Schleiffer, Christine; Klingelhöfer, Lisa; Schneider, Christine; Proft, Florian; Schwanebeck, Uta; Reichmann, Heinz; Riederer, Peter; Storch, Alexander

    2012-11-01

    A previous questionnaire study suggests an increased chocolate consumption in Parkinson's disease (PD). The cacao ingredient contains caffeine analogues and biogenic amines, such as β-phenylethylamine, with assumed antiparkinsonian effects. We thus tested the effects of 200 g of chocolate containing 80 % of cacao on UPDRS motor score after 1 and 3 h in 26 subjects with moderate non-fluctuating PD in a mono-center, single-dose, investigator-blinded crossover study using cacao-free white chocolate as placebo comparator. At 1 h after chocolate intake, mean UPDRS motor scores were mildly decreased compared to baseline in both treatments with significant results only for dark chocolate [-1.3 (95 % CI 0.18-2.52, RMANOVA F = 4.783, p = 0.013¸ Bonferroni p = 0.021 for 1 h values)]. A 2 × 2-cross-over analysis revealed no significant differences between both treatments [-0.54 ± 0.47 (95 % CI -1.50 to 0.42), p = 0.258]. Similar results were obtained at 3 h after intake. β-phenylethylamine blood levels were unaltered. Together, chocolate did not show significant improvement over white cacao-free chocolate in PD motor function.

  20. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis

    DEFF Research Database (Denmark)

    Falah, M; Madsen, C; Holbech, J V

    2012-01-01

    sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well....... Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample...... of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non...

  1. Resveratrol does not influence metabolic risk markers related to cardiovascular health in overweight and slightly obese subjects: a randomized, placebo-controlled crossover trial.

    Directory of Open Access Journals (Sweden)

    Sanne M van der Made

    Full Text Available In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking.The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function.This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25 and women (n = 20 with a mean age of 61 ± 7 years. Subjects received in random order resveratrol (150 mg per day or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period.Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean ± SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 ± 0.12 g/L (P = 0.791, apoB100; -0.01 ± 0.11 g/L (P = 0.545, HDL cholesterol; 0.00 ± 0.09 mmol/L (P = 0.721, LDL cholesterol -0.03 ± 0.57 mmol/L (P = 0.718, triacylglycerol; 0.10 ± 0.54 mmol/L (P = 0.687, glucose; -0.08 ± 0.28 mmol/L (P = 0.064, insulin; -0.3 ± 2.5 mU/L (P = 0.516. Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed.150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study.ClinicalTrials.gov NCT01364961.

  2. Investigation of the potentiation of the analgesic effects of fentanyl by ketamine in humans: a double-blinded, randomised, placebo controlled, crossover study of experimental pain[ISRCTN83088383

    Directory of Open Access Journals (Sweden)

    Nadeson Raymond

    2005-04-01

    Full Text Available Abstract Background Despite preclinical evidence suggesting a synergistic interaction between ketamine and opioids promoting analgesia, several clinical trials have not identified dosing regimens capable of eliciting a benefit in the co-administration of ketamine with opioids. Methods Ten healthy volunteers participated in a double blinded, randomised, placebo controlled, crossover laboratory study in order to determine whether a low dose of ketamine potentiated the antinociceptive effect of fentanyl without causing an increase in sedative effects. A battery of tests was used to assess both nociception and sedation including electrical current, pressure, thermal stimuli, psychometric tests, and both subjective and objective scores of sedation. Target controlled infusions of the study drugs were used. Ketamine and fentanyl were administered alone and in combination in a double-blinded randomised crossover design. Saline was used as the control, and propofol was used to validate the tests of sedation. Cardiovascular and respiratory parameters were also assessed. Results The electrical current pain threshold dose response curve of fentanyl combined with ketamine was markedly steeper than the dose response curve of fentanyl alone. While a ketamine serum concentration of 30 ng/ml did not result in a change in electrical pain threshold when administered alone, when it was added to fentanyl, the combination resulted in greater increase in pain threshold than that of fentanyl administered alone. When nociception was assessed using heat and pressure stimuli, ketamine did not potentiate the anti-nociceptive effect of fentanyl. There was no difference between the sedative effect of fentanyl and fentanyl in combination with ketamine as assessed by both subjective and objective measures of sedation. Cardiovascular and respiratory parameters were unaffected by the study drugs at the doses given. Conclusion A serum concentration of ketamine that did not alter

  3. Are all placebo effects equal? Placebo pills, sham acupuncture, cue conditioning and their association.

    Directory of Open Access Journals (Sweden)

    Jian Kong

    Full Text Available Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol, sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for "placebo responders." However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non

  4. Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled, cross-over trial.

    Science.gov (United States)

    Jørgensen, Mette Rose; Keller, Mette Kirstine; Kragelund, Camilla; Hamberg, Kristina; Ericson, Dan; Nielsen, Claus Henrik; Twetman, Svante

    2016-07-01

    To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. The study group consisted of 47 healthy adults (18-32 years) who volunteered for a randomized, double-blind, placebo-controlled, cross-over trial after informed consent. During intervention, the subjects ingested two lozenges per day containing two strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo lozenges. The intervention and wash-out periods were 3 weeks. Saliva samples were collected at baseline, immediately after each intervention period and 3 weeks post-intervention. ELISA was used to measure sIgA and luminex technology was used to measure the interleukins (IL)-1β, IL-6, IL-8 and IL-10. For statistical analyses a mixed ANOVA model was employed to calculate changes in the salivary outcome variables. Forty-one subjects completed the study and reported a good compliance. No significant differences in the concentrations of salivary sIgA or cytokines were recorded between the L. reuteri and placebo interventions or between baseline and 3 weeks post-intervention levels. No side- or adverse effects were reported. Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L. reuteri do not seem to modulate the salivary oral immune response in healthy young subjects (ClinicalTrials.gov NCT02017886).

  5. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

    Science.gov (United States)

    Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

    2013-07-01

    Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

    2016-01-01

    It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

  7. Effects of carbohydrates-BCAAs-caffeine ingestion on performance and neuromuscular function during a 2-h treadmill run: a randomized, double-blind, cross-over placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Peltier Sébastien L

    2011-12-01

    Full Text Available Abstract Background Carbohydrates (CHOs, branched-chain amino acids (BCAAs and caffeine are known to improve running performance. However, no information is available on the effects of a combination of these ingredients on performance and neuromuscular function during running. Methods The present study was designed as a randomized double-blind cross-over placebo-controlled trial. Thirteen trained adult males completed two protocols, each including two conditions: placebo (PLA and Sports Drink (SPD: CHOs 68.6 g.L-1, BCAAs 4 g.L-1, caffeine 75 mg.L-1. Protocol 1 consisted of an all-out 2 h treadmill run. Total distance run and glycemia were measured. In protocol 2, subjects exercised for 2 h at 95% of their lowest average speeds recorded during protocol 1 (whatever the condition. Glycemia, blood lactate concentration and neuromuscular function were determined immediately before and after exercise. Oxygen consumption (V˙O2, heart rate (HR and rate of perceived exertion (RPE were recorded during the exercise. Total fluids ingested were 2 L whatever the protocols and conditions. Results Compared to PLA, ingestion of SPD increased running performance (p = 0.01, maintained glycemia and attenuated central fatigue (p = 0.04, an index of peripheral fatigue (p = 0.04 and RPE (p = 0.006. Maximal voluntary contraction, V˙O2, and HR did not differ between the two conditions. Conclusions This study showed that ingestion of a combination of CHOs, BCAAs and caffeine increased performance by about 2% during a 2-h treadmill run. The results of neuromuscular function were contrasted: no clear cut effects of SPD were observed. Trial registration ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00799630

  8. Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.

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    Lamport, Daniel J; Lawton, Clare L; Merat, Natasha; Jamson, Hamish; Myrissa, Kyriaki; Hofman, Denise; Chadwick, Helen K; Quadt, Frits; Wightman, JoLynne D; Dye, Louise

    2016-03-01

    Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for ≥30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy-, taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within

  9. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Indika Edirisinghe

    2012-12-01

    Full Text Available Objective: This investigation was undertaken to determine whether a grape seed extract (GSE that is rich in mono-, oligo- and poly- meric polyphenols would modify postprandial oxidative stress and inflammation in individuals with the metabolic syndrome (MetS.Background: MetS is known to be associated with impaired glucose tolerance and poor glycemic control. Consumption of a meal high in readily available carbohydrates and fat causes postprandial increases in glycemia and lipidemia and markers of oxidative stress, inflammation and insulin resistance. Materials/methods: After an overnight fast, twelve subjects with MetS (5 men and 7 women consumed a breakfast meal high in fat and carbohydrate in a cross-over design. A GSE (300 mg or placebo capsule was administrated 1 hr before the meal (-1 hr. Changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 hr. Results: Plasma hydrophilic oxygen radical absorbance capacity (ORAC measured as the positive incremental area under the curve (-1 to 5 hr was significantly increased when the meal was preceded by GSE compared with placebo (P0.05. No changes in inflammatory markers were evident. Conclusion: These data suggest that GSE enhances postprandial plasma antioxidant status and reduces the glycemic response to a meal, high in fat and carbohydrate in subjects with the MetS.

  10. Double-blind, placebo-controlled study of intravenous prostacyclin on hemodynamics in severe Raynaud's phenomenon: the acute vasodilatory effect is not sustained.

    Science.gov (United States)

    Kingma, K; Wollersheim, H; Thien, T

    1995-09-01

    In 12 patients with severe Raynaud's phenomenon (RP: ischemic ulcers or intractable pain despite use of narcotic analgetics), we studied the acute and long-term hemodynamic effects of epoprostenol on systemic and finger skin circulation. Epoprostenol was infused intravenously (i.v., initial infusion rate of 2 ng/kg/min, with a subsequent increase of 2 ng/kg/min every 30 min to the individually tolerated maximal dose of 8 ng/kg/min) in a triple, 5-h, double-blind, placebo-controlled cross-over study. During epoprostenol infusion, systolic blood pressure (SBP) remained stable, while diastolic BP (DBP) decreased (-8 mm Hg, p Forearm blood flow (FBF) increased and forearm vascular resistance (FVR) decreased during epoprostenol as compared with placebo infusion (p cooling test of the hand as compared with placebo. The increase in transcutaneous oxygen tension reached significant difference only during recovery (p cooling tests performed 1 and 6 weeks after the completed epoprostenol or placebo triple-infusion cycle. Repeated long-lasting epoprostenol infusion immediately improves the microcirculation, but these effects are not sustained after 1 week.

  11. Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study.

    Science.gov (United States)

    Kochiadakis, G E; Kanoupakis, E M; Kalebubas, M D; Igoumenidis, N E; Vardakis, K E; Mavrakis, H E; Vardas, P E

    2001-01-01

    To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation. The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

  12. Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.

    Science.gov (United States)

    Nakanjako, Damalie; Ssinabulya, Isaac; Nabatanzi, Rose; Bayigga, Lois; Kiragga, Agnes; Joloba, Moses; Kaleebu, Pontiano; Kambugu, Andrew D; Kamya, Moses R; Sekaly, Rafick; Elliott, Alison; Mayanja-Kizza, Harriet

    2015-03-01

    T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery. A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry. Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported. Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa. © 2014 John Wiley & Sons Ltd.

  13. Inorganic Nitrate in Angina Study: A Randomized Double-Blind Placebo-Controlled Trial.

    Science.gov (United States)

    Schwarz, Konstantin; Singh, Satnam; Parasuraman, Satish K; Rudd, Amelia; Shepstone, Lee; Feelisch, Martin; Minnion, Magdalena; Ahmad, Shakil; Madhani, Melanie; Horowitz, John; Dawson, Dana K; Frenneaux, Michael P

    2017-09-08

    In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P =0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P =0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012-000196-17. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  14. Effects of a hops (Humulus lupulus L.) dry extract supplement on self-reported depression, anxiety and stress levels in apparently healthy young adults: a randomized, placebo-controlled, double-blind, crossover pilot study.

    Science.gov (United States)

    Kyrou, Ioannis; Christou, Aimilia; Panagiotakos, Demosthenes; Stefanaki, Charikleia; Skenderi, Katerina; Katsana, Konstantina; Tsigos, Constantine

    2017-04-01

    The Humulus lupulus L. plant (hops) is used as a herbal medicinal product for anxiety/mood disorders. Our aim was to study the effects of a hops dry extract on self-reported depression, anxiety and stress levels in young adults. Apparently healthy young adults from our university completed the Depression Anxiety Stress Scale-21 (DASS-21) and those reporting at least mild depression, anxiety and stress were invited to complete the study intervention. This followed a randomized (1:1), placebo-controlled, double-blind, crossover design with two 4-week intervention periods (Melcalin hops or placebo; two 0.2 gr capsules once daily) separated by a 2-week wash-out. Anthropometric measurements, DASS-21 assessments and measurements of morning cortisol plasma levels were performed at the beginning and the end of the 4-week treatment periods. 36 participants (Females/Males: 31/5; age: 24.7±0.5 years) completed the study intervention (attrition: 6/42). No significant changes in body weight and composition or morning circulating cortisol were noted with the hops or placebo. Significantly decreased DASS-21 anxiety, depression and stress scores were documented with hops (9.2±7.3 vs. 5.1±5.9, 11.9±7.9 vs. 9.2±7.4, and 19.1±8.1 vs. 11.6±8.1; all p values depression, anxietyand stress symptoms, daily supplementation with a hops dry extract can significantly improve all these symptoms over a 4-week period. These beneficial effects agree with the indication of hops for anxiety/mood disorders and restlessness, as approved by the German Commission E.

  15. Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

    Science.gov (United States)

    Dalai, Shebani Sethi; Adler, Sarah; Najarian, Thomas; Safer, Debra Lynn

    2018-01-01

    Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Efficacy and safety of premedication with single dose of oral pregabalin in children with dental anxiety: A randomized double-blind placebo-controlled crossover clinical trial

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    Tahereh Eskandarian

    2015-01-01

    Full Text Available Background: Dental anxiety is a relatively frequent problem that can lead to more serious problems such as a child entering a vicious cycle as he/she becomes reluctant to accept the required dental treatments. The aim of this randomized double-blind clinical trial study was to evaluate the anxiolytic and sedative effect of pregabalin in children. Materials and Methods: Twenty-five children were randomized to a double-blind placebo-controlled crossover clinical trial. Two visits were scheduled for each patient. At the first visit, 75 mg pregabalin or placebo was given randomly, and the alternative was administered at the next visit. Anxiolytic and sedative effects were measured using the visual analogue scale. The child′s behavior was rated with the Frankl behavioral rating scale and the sedation level during the dental procedure was scored using the Ramsay sedation scale. The unpaired, two-tailed Student′s t-test was used to compare the mean changes of visual analog scale (VAS for anxiety in the pregabalin group with that of the placebo group. A repeated measures MANOVA model was used to detect differences in sedation level in the pregabalin and placebo groups regarding the interaction of 3-time measurements; sub-group analysis was performed using Student′s t-test. The Mann-Whitney U-test was used to analyze the nonparametric data of the Frankl and Ramsay scales. A P < 0.05 was considered significant. Results: The reduction of the VAS-anxiety score from 2 h post-dose was statistically significant in the pregabalin group. From 2 h to 4 h post-dose, the VAS-sedation score increased significantly in the pregabalin group. The child′s behavior rating was not significantly different between the groups. The number of "successful" treatment visits was higher in the pregabalin group compared to the placebo group. Conclusion: Significant anxiolytic and sedative effects can be anticipated 2 h after oral administration of pregabalin without serious

  17. Blueberry effects on dark vision and recovery after photobleaching: placebo-controlled crossover studies.

    Science.gov (United States)

    Kalt, Wilhelmina; McDonald, Jane E; Fillmore, Sherry A E; Tremblay, Francois

    2014-11-19

    Clinical evidence for anthocyanin benefits in night vision is controversial. This paper presents two human trials investigating blueberry anthocyanin effects on dark adaptation, functional night vision, and vision recovery after retinal photobleaching. One trial, S2 (n = 72), employed a 3 week intervention and a 3 week washout, two anthocyanin doses (271 and 7.11 mg cyanidin 3-glucoside equivalents (C3g eq)), and placebo. The other trial, L1 (n = 59), employed a 12 week intervention and an 8 week washout and tested one dose (346 mg C3g eq) and placebo. In both S2 and L1 neither dark adaptation nor night vision was improved by anthocyanin intake. However, in both trials anthocyanin consumption hastened the recovery of visual acuity after photobleaching. In S2 both anthocyanin doses were effective (P = 0.014), and in L1 recovery was improved at 8 weeks (P = 0.027) and 12 weeks (P = 0.030). Although photobleaching recovery was hastened by anthocyanins, it is not known whether this improvement would have an impact on everyday vision.

  18. Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

    Science.gov (United States)

    Hammami, Muhammad M; Yusuf, Ahmed; Shire, Faduma S; Hussein, Rajaa; Al-Swayeh, Reem

    2017-05-23

    Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t ½ ) (primary outcome), maximum concentration (C max ), C max first time (T max ), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC T ), extrapolated to infinity (AUC I ), or to T max of overt drug (AUC Overttmax ), and C max /AUC I were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC T , AUC I , C max , AUC Overttmax , and C max /AUC I were within the bioequivalence range, except

  19. Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

    Directory of Open Access Journals (Sweden)

    Burbank F

    2014-02-01

    Full Text Available Fred Burbank Salt Creek International Women's Health Foundation, San Clemente, CA, USA Purpose: To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials. Patients and methods: Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes. Results: For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Qbetween subgroups =0.25, PQ≥0.62. Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Qbetween subgroups =4.59, PQ≤0.03 and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Qbetween subgroups =5.50, PQ≤0.02. Conclusion: For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials. Keywords: sham effect, placebo effect, trial design, crossover study, parallel study, counterstimulation

  20. Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents

    Science.gov (United States)

    Johnson, Mats; Ostlund, Sven; Fransson, Gunnar; Kadesjo, Bjorn; Gillberg, Christopher

    2009-01-01

    Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD…

  1. A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood

    OpenAIRE

    Dodd, Fiona; Kennedy, David; Riby, Leigh; Haskell, Crystal

    2015-01-01

    Rationale -Evidence suggests interactive effects of the tea components caffeine and L-theanine on behaviour, yet no data exists exploring the impact of the two on cerebral blood flow (CBF).\\ud \\ud Objectives - The current placebo-controlled, double-blind, counterbalanced, crossover study examined the effects of caffeine and L-theanine on CBF and extended previous cognitive and mood findings by using lower doses than previous studies of a similar methodology, which more closely reflect the rat...

  2. Inverse Effects of Oxytocin on Attributing Mental Activity to Others in Depressed and Healthy Subjects: A Double-Blind Placebo Controlled fMRI Study.

    Directory of Open Access Journals (Sweden)

    David Pincus

    2010-10-01

    Full Text Available Background: Oxytocin is a stress-attenuating and pro-social neuropeptide. To date, no study has looked at the effects of oxytocin in modulating brain activity in depressed individuals nor attempted to correlate this activity with attribution of mental activity in others. Method: We enrolled 10 unmedicated depressed adults and 10 matched healthy controls in a crossover, double blind placebo controlled fmri 40 i.u. intra-nasal oxytocin study (20 i.u. per nostril. Each subject performed Reading the Mind in the Eyes task (RMET before and after inhalation of oxytocin or placebo control for a total of 80 scans. Results: Before oxytocin administration, RMET engaged medial and lateral prefrontal cortex, amygdala, insula and associative areas. Depressed subjects showed increased anterior ventral activation for the RMET minus gender identification contrast whereas matched controls showed increased dorsal and frontal activity. Compared to placebo, oxytocin in depressed subjects showed increased activity in the superior middle frontal gyrus and insula, while controls exhibited more activity in ventral regions. Oxytocin also led to inverse effects in reaction times on attribution task between groups, with controls getting faster and depressed individuals slower to respond. Conclusion: Depression is associated with increased paralimbic activity during emotional mental attribution of others, appearing to be distinctly modulated by oxytocin when compared to healthy controls. Further studies are needed to explore long-term exposure to pro-social neuropeptides on mood in depressed populations and assess their clinical relevance.

  3. Placebo-Controlled Study of Pimozide Augmentation of Fluoxetine in Body Dysmorphic Disorder

    Science.gov (United States)

    Phillips, Katharine A.

    2006-01-01

    Objective Although body dysmorphic disorder often responds to serotonin reuptake inhibitors (SRIs), most patients do not respond or respond only partially. However, placebo-controlled studies of augmentation of SRIs have not been done. Furthermore, although 40%–50% of patients are delusional, studies of antipsychotic medications have not been done. Method Twenty-eight patients with body dysmorphic disorder or its delusional variant participated in an 8-week, placebo-controlled, double-blind, parallel-group study of pimozide augmentation of fluoxetine. Results Pimozide was not more effective than placebo: two (18.2%) of 11 subjects responded to pimozide and three (17.6%) of 17 subjects responded to placebo. There was no significant effect of baseline delusionality on endpoint severity of body dysmorphic disorder. Delusionality did not decrease significantly more with pimozide than placebo. Conclusions Pimozide augmentation of fluoxetine treatment for body dysmorphic disorder was not more effective than placebo, even in more delusional patients. Further studies of augmentation for SRIs are needed. PMID:15677604

  4. Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

    DEFF Research Database (Denmark)

    Gall, M A; Rossing, P; Skøtt, P

    1992-01-01

    The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

  5. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    Directory of Open Access Journals (Sweden)

    Mason JW

    2014-03-01

    Full Text Available Jay W Mason,1 Thomas E Moon,2 Erin O’Boyle,3 Albert Dietz41Department of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc., San Carlos, CA, 3AP Pharma, Redwood City, CA, 4Spaulding Clinical Research, West Bend, WI, USABackground: Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO, intravenous (IV, and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.Methods: This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.Results: The upper one-sided 95% confidence interval (CI for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36 at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours and slow elimination (mean half-life 18.6 hours

  6. Vapocoolant Spray vs Lidocaine/Prilocaine Cream for Reducing the Pain of Venipuncture in Hemodialysis Patients: A Randomized, Placebo-Controlled, Crossover Study

    OpenAIRE

    ?elik, G?lperi; ?zbek, Orhan; Y?lmaz, M?mtaz; Duman, Ipek; ?zbek, Seda; Apiliogullari, Seza

    2011-01-01

    Objective: Patients undergoing hemodialysis are repeatedly exposed to stress and pain from approximately 300 punctures per year to their arteriovenous fistula. This study was designed to measure pain associated with venepuncture during AVF cannulation and to compare the effectiveness of ethyl chloride vapocoolant spray, topical eutectic mixture of local anesthetics (EMLA) cream and placebo in controlling pain caused by venepuncture of arteriovenous fistula patients undergoing chronic hemodial...

  7. A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption

    Directory of Open Access Journals (Sweden)

    Kokubo Takeshi

    2013-02-01

    Full Text Available Abstract Background Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism. Methods This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA, and a profile of mood states (POMS and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase. In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption. Results There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism. Conclusions Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the

  8. Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial.

    Science.gov (United States)

    Kuppens, R J; Donze, S H; Hokken-Koelega, A C S

    2016-12-01

    Prader-Willi syndrome (PWS) is known for hyperphagia with impaired satiety and a specific behavioural phenotype with stubbornness, temper tantrums, manipulative and controlling behaviour and obsessive-compulsive features. PWS is associated with hypothalamic and oxytocinergic dysfunction. In humans without PWS, intranasal oxytocin administration had positive effects on social and eating behaviour, and weight balance. To evaluate the effects of intranasal oxytocin compared to placebo administration on social behaviour and hyperphagia in children with PWS. Randomized, double-blind, placebo-controlled, crossover study in a PWS Reference Center in the Netherlands. Crossover intervention with twice daily intranasal oxytocin (dose range 24-48 IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS (aged 6 to 14 years). In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found, but in the 17 children younger than 11 years, parents reported significantly less anger (P = 0·001), sadness (P = 0·005), conflicts (P = 0·010) and food-related behaviour (P = 0·011), and improvement of social behaviour (P = 0·018) during oxytocin treatment compared with placebo. In the eight children older than 11 years, the items happiness (P = 0·039), anger (P = 0·042) and sadness (P = 0·042) were negatively influenced by oxytocin treatment compared to placebo. There were no side effects or adverse events. This randomized, double-blind, placebo-controlled study suggests that intranasal oxytocin administration has beneficial effects on social behaviour and food-related behaviour in children with PWS younger than 11 years of age, but not in those older than 11 years of age. © 2016 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

  9. Importance of placebo effect in cough clinical trials.

    Science.gov (United States)

    Eccles, Ron

    2010-01-01

    Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed.

  10. Intravesical Capsaicin in Patients with Detrusor Hyper-reflexia. A Placebo-controlled Cross-over Study

    DEFF Research Database (Denmark)

    Petersen, T; Nielsen, J B; Schrøder, H D

    1999-01-01

    to anticholinergic treatment underwent intravesical administration of 50 ml 2% lignocaine. followed by either 100 ml 1 mmol/l capsaicin or 100 ml physiological saline for 30 min. Cross-over to the alternative treatment took place after 4 weeks. Varying degrees of burning sensation were experienced by all but one...... patient during the capsaicin treatment and precluded the possibility of conducting studies of this type in a blind manner. No preference for capsaicin treatment was found, and micturition and VAS scores were unchanged after treatment with capsaicin. The mean volume of the contents of the bladder at which...... DH first appeared was 175 ml after saline and 195 ml after capsaicin (mean difference 20 ml with a 5% confidence interval from -25 to 65). Bladder biopsies taken 2 weeks after treatment with capsaicin showed more pronounced inflammation, superficial haemorrhage, squamous epithelial metaplasia...

  11. Effects of alprazolam on driving ability, memory functioning and psychomotor performance: a randomized, placebo-controlled study.

    Science.gov (United States)

    Verster, Joris C; Volkerts, Edmund R; Verbaten, Marinus N

    2002-08-01

    Alprazolam is prescribed for the treatment of anxiety and panic disorder. Most users are presumably involved in daily activities such as driving. However, the effects of alprazolam on driving ability have never been investigated. This study was conducted to determine the effects of alprazolam (1 mg) on driving ability, memory and psychomotor performance. Twenty healthy volunteers participated in a randomized, double-blind, placebo-controlled crossover study. One hour after oral administration, subjects performed a standardized driving test on a primary highway during normal traffic. They were instructed to drive with a constant speed (90 km/h) while maintaining a steady lateral position within the right traffic lane. Primary performance measures were the Standard Deviation of Lateral Position (SDLP) and the Standard Deviation of Speed (SDS). After the driving test, subjective driving quality, mental effort, and mental activation during driving were assessed. A laboratory test battery was performed 2.5 h after treatment administration, comprising the Sternberg Memory Scanning Test, a Continuous Tracking Test, and a Divided Attention Test. Relative to placebo, alprazolam caused serious driving impairment, as expressed by a significantly increased SDLP (F(1,19) = 97.3, p driving quality (F(1,19) = 16.4, p driving (F(1,19) = 26.4, p drive an automobile or operate potentially dangerous machinery.

  12. Does different information disclosure on placebo control affect blinding and trial outcomes? A case study of participant information leaflets of randomized placebo-controlled trials of acupuncture

    Directory of Open Access Journals (Sweden)

    Soyeon Cheon

    2018-01-01

    Full Text Available Abstract Background While full disclosure of information on placebo control in participant information leaflets (PILs in a clinical trial is ethically required during informed consent, there have been concerning voices such complete disclosures may increase unnecessary nocebo responses, breach double-blind designs, and/or affect direction of trial outcomes. Taking an example of acupuncture studies, we aimed to examine what participants are told about placebo controls in randomized, placebo-controlled trials, and how it may affect blinding and trial outcomes. Methods Authors of published randomized, placebo-controlled trials of acupuncture were identified from PubMed search and invited to provide PILs for their trials. The collected PILs were subjected to content analysis and categorized based on degree of information disclosure on placebo. Blinding index (BI as a chance-corrected measurement of blinding was calculated and its association with different information disclosure was examined. The impact of different information disclosure from PILs on primary outcomes was estimated using a random effects model. Results In 65 collected PILs, approximately 57% of trials fully informed the participants of placebo control, i.e. full disclosure, while the rest gave deceitful or no information on placebo, i.e. no disclosure. Placebo groups in the studies with no disclosure tended to make more opposite guesses on the type of received intervention than those with disclosure, which may reflect wishful thinking (BI −0.21 vs. −0.16; p = 0.38. In outcome analysis, studies with no disclosure significantly favored acupuncture than those with full disclosure (standardized mean difference − 0.43 vs. −0.12; p = 0.03, probably due to enhanced expectations. Conclusions How participants are told about placebos can be another potential factor that may influence participant blinding and study outcomes by possibly modulating patient expectation. As we

  13. Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial.

    Science.gov (United States)

    Faridi, Zubaida; Njike, Valentine Yanchou; Dutta, Suparna; Ali, Ather; Katz, David L

    2008-07-01

    Studies suggest cardioprotective benefits of dark chocolate containing cocoa. This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.

  14. Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

    Science.gov (United States)

    Takiguchi, Kazuo; Uezato, Akihito; Itasaka, Michio; Atsuta, Hidenori; Narushima, Kenji; Yamamoto, Naoki; Kurumaji, Akeo; Tomita, Makoto; Oshima, Kazunari; Shoda, Kosaku; Tamaru, Mai; Nakataki, Masahito; Okazaki, Mitsutoshi; Ishiwata, Sayuri; Ishiwata, Yasuyoshi; Yasuhara, Masato; Arima, Kunimasa; Ohmori, Tetsuro; Nishikawa, Toru

    2017-07-12

    It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

  15. The Effect of Buffering High Acid Load Meal with Sodium Bicarbonate on Postprandial Glucose Metabolism in Humans-A Randomized Placebo-Controlled Study.

    Science.gov (United States)

    Kozan, Pinar; Blythe, Jackson C; Greenfield, Jerry R; Samocha-Bonet, Dorit

    2017-08-11

    Background: High dietary acid load relates to increased risk of type 2 diabetes in epidemiological studies. We aimed to investigate whether buffering a high acid load meal with an alkalizing treatment changes glucose metabolism post meal. Methods: Non-diabetic participants ( n = 32) were randomized to receive either 1680 mg NaHCO₃ or placebo, followed by a high acid load meal in a double-blind placebo-controlled crossover (1-4 weeks apart) study. Thirty (20 men) participants completed the study. Venous blood pH, serum bicarbonate, blood glucose, serum insulin, C -peptide, non-esterified fatty acid (NEFA), and plasma glucagon-like peptide-1 (GLP-1) concentrations were measured at baseline (fasting) and at 15-30 min intervals for 3 h post meal. Results: The treatment was well tolerated. Venous blood pH declined in the first 15 min post meal with the placebo ( p = 0.001), but not with NaHCO₃ ( p = 0.86) and remained decreased with the placebo for 3 h ( p interaction = 0.04). On average over the 3 h blood pH iAUC was greater with NaHCO₃ compared with placebo ( p = 0.02). However, postprandial glucose, insulin, C -peptide, NEFA and GLP-1 were not different between treatments ( p interaction ≥ 0.07). Conclusions: An alkalizing medication administered pre-meal has no acute effect on glycaemia and insulin response in healthy individuals. Long-term interventions in at-risk populations are necessary to investigate the effect of sustained alkalization on glucose metabolism.

  16. Effects of polydextrose with breakfast or with a midmorning preload on food intake and other appetite-related parameters in healthy normal-weight and overweight females: An acute, randomized, double-blind, placebo-controlled, and crossover study.

    Science.gov (United States)

    Ibarra, Alvin; Olli, Kaisa; Pasman, Wilrike; Hendriks, Henk; Alhoniemi, Esa; Raza, Ghulam Shere; Herzig, Karl-Heinz; Tiihonen, Kirsti

    2017-03-01

    Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females. Per earlier studies, the primary outcome was defined as the difference in subsequent EI when PDX was consumed at midmorning versus placebo. Thirty-two volunteers were enrolled in this acute, double-blind, placebo-controlled, randomized, and crossover trial to examine the effects of 12.5 g of PDX, administered as part of a breakfast or midmorning preload, on subsequent EI, subjective feelings of appetite, well-being, and mood. Gastric emptying rates and the blood concentrations of glucose, insulin, cholecystokinin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine-tyrosine were measured in the group that received PDX as part of their breakfast. There were no differences in EI between volunteers who were fed PDX and placebo. PDX intake with breakfast tended to elevate blood glucose (P = 0.06) during the postabsorptive phase, significantly lowered insulin by 15.7% (P = 0.04), and increased GLP-1 by 39.9% (P = 0.02); no other effects on blood parameters or gastric emptying rates were observed. PDX intake at midmorning reduced hunger by 31.4% during the satiation period (P = 0.02); all other subjective feelings of appetite were unaffected. Volunteers had a uniform mood profile during the study. PDX was well tolerated, causing one mild adverse event throughout the trial. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. A polysomnographic placebo-controlled evaluation of the efficacy and safety of eszopiclone relative to placebo and zolpidem in the treatment of primary insomnia.

    Science.gov (United States)

    Erman, Milton K; Zammit, Gary; Rubens, Robert; Schaefer, Kendyl; Wessel, Thomas; Amato, David; Caron, Judy; Walsh, James K

    2008-06-15

    To evaluate the polysomnographic efficacy and the safety of a range of doses of eszopiclone relative to placebo in patients with primary insomnia. Zolpidem 10 mg was included as an active control. This multicenter, randomized, crossover study enrolled patients aged 21-64 years meeting the DSM-IV criteria for primary insomnia (n = 65). Patients received 2 nights treatment each with placebo, eszopiclone 1 mg, 2 mg, 2.5 mg, or 3 mg, and zolpidem 10 mg after randomization to one of 6 treatment sequences. Visits were separated by a 3-7 day washout. Objective efficacy was assessed by polysomnography (PSG). The primary endpoint was latency to persistent sleep (LPS); key secondary endpoints were sleep efficiency (SE) and wake time after sleep onset (WASO); other endpoints included wake time during sleep (WTDS) and number of awakenings (NAW), as well as patient-reported variables. LPS and SE were significantly different than placebo for all active treatments (p zolpidem 10 mg or the other eszopiclone doses. The incidence of central nervous system adverse events was 23.4% for zolpidem 10 mg, 6.2% to 12.5% for the eszopiclone doses, and 7.9% for placebo. Relative to placebo, all active treatments were effective in reducing LPS and increasing SE. Eszopiclone 3 mg was significantly different from placebo on the 3 PSG measures of sleep maintenance (WASO, WTDS, and NAW). Significant differences between zolpidem 10 mg and eszopiclone (2 mg or 3 mg) were not observed for PSG-measured outcomes, although the study was not powered to detect differences between the active drug conditions.

  18. Effect of supplementation of fermented milk drink containing probiotic Lactobacillus casei Shirota on the concentrations of aflatoxin biomarkers among employees of Universiti Putra Malaysia: a randomised, double-blind, cross-over, placebo-controlled study.

    Science.gov (United States)

    Mohd Redzwan, Sabran; Abd Mutalib, Mohd Sokhini; Wang, Jia-Sheng; Ahmad, Zuraini; Kang, Min-Su; Abdul Rahman, Nurul 'Aqilah; Nikbakht Nasrabadi, Elham; Jamaluddin, Rosita

    2016-01-14

    Human exposure to aflatoxin is through the diet, and probiotics are able to bind aflatoxin and prevent its absorption in the small intestine. This study aimed to determine the effectiveness of a fermented milk drink containing Lactobacillus casei Shirota (LcS) (probiotic drink) to prevent aflatoxin absorption and reduce serum aflatoxin B1-lysine adduct (AFB1-lys) and urinary aflatoxin M1 concentrations. The present study was a randomised, double-blind, cross-over, placebo-controlled study with two 4-week intervention phases. In all, seventy-one subjects recruited from the screening stage were divided into two groups--the Yellow group and the Blue group. In the 1st phase, one group received probiotic drinks twice a day and the other group received placebo drinks. Blood and urine samples were collected at baseline, 2nd and 4th week of the intervention. After a 2-week wash-out period, the treatments were switched between the groups, and blood and urine samples were collected at the 6th, 8th and 10th week (2nd phase) of the intervention. No significant differences in aflatoxin biomarker concentrations were observed during the intervention. A within-group analysis was further carried out. Aflatoxin biomarker concentrations were not significantly different in the Yellow group. Nevertheless, ANOVA for repeated measurements indicated that AFB1-lys concentrations were significantly different (P=0·035) with the probiotic intervention in the Blue group. The 2nd week AFB1-lys concentrations (5·14 (SD 2·15) pg/mg albumin (ALB)) were significantly reduced (P=0·048) compared with the baseline (6·24 (SD 3·42) pg/mg ALB). Besides, the 4th week AFB1-lys concentrations were significantly lower (P<0·05) with probiotic supplementation than with the placebo. Based on these findings, a longer intervention study is warranted to investigate the effects of continuous LcS consumption to prevent dietary aflatoxin exposure.

  19. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

    Science.gov (United States)

    Dower, James I; Geleijnse, Johanna M; Gijsbers, Lieke; Zock, Peter L; Kromhout, Daan; Hollman, Peter C H

    2015-05-01

    Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea). We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health. Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function. Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors. Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study

  20. Male hormonal contraception: a double-blind, placebo-controlled study.

    NARCIS (Netherlands)

    Mommers, E.; Kersemaekers, W.M.; Elliesen, J.; Kepers, M.; Apter, D.; Behre, H.M.; Beynon, J.; Bouloux, P.M.; Costantino, A.; Gerbershagen, H.P.; Gronlund, L.; Heger-Mahn, D.; Huhtaniemi, I.; Koldewijn, E.L.; Lange, C.; Lindenberg, S.; Meriggiola, M.C.; Meuleman, E.J.H.; Mulders, P.F.A.; Nieschlag, E.; Perheentupa, A.; Solomon, A.; Vaisala, L.; Wu, F.C.; Zitzmann, M.

    2008-01-01

    BACKGROUND: This study was performed to assess spermatogenesis suppression and safety of a new combination of an etonogestrel (ENG) implant combined with testosterone undecanoate (TU) injections for male contraception. This is the first large placebo-controlled study for male hormonal contraception.

  1. Improvement in exercise duration, lung function and well-being in G551D-cystic fibrosis patients: a double-blind, placebo-controlled, randomized, cross-over study with ivacaftor treatment.

    Science.gov (United States)

    Edgeworth, Deirdre; Keating, Dominic; Ellis, Matthew; Button, Brenda; Williams, Elyssa; Clark, Denise; Tierney, Audrey; Heritier, Stephane; Kotsimbos, Tom; Wilson, John

    2017-08-01

    G551D, a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in CF is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of V O 2 max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, body mass index (BMI), sweat chloride and disease-specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %Δ V O 2 max was unchanged compared with placebo as was %Δminute ventilation. However, %Δexercise time (mean 7.3, CI 0.5-14,1, P =0.0222) significantly increased as did %ΔFEV 1 (11.7%, range 5.3-18.1, P <0·005) and %ΔBMI (1.2%, range 0.1-2.3, P =0·0393) whereas sweat chloride decreased (mean -43.4; range -55.5-18.1 mmol·l -1 , P <0·005). Total and activity based domains in both CFQ-R and AWEscore also increased. A positive treatment effect on spirometry, BMI (increased), SCT (decreased) and total and activity based CF-specific QOL measures was expected. However, the lack of discernible improvement in V O 2 max and VE despite other positive changes including spirometric lung function and exercise time with a 28-day ivacaftor intervention suggests that ventilatory parameters are not the sole driver of change in exercise capacity in this study cohort. Investigation over a more prolonged period may delineate the potential interdependencies of the observed discordances over time. ClinicalTrials.gov-NCT01937325. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  2. Effects of Milnacipran on Neurocognition, Pain, and Fatigue in Fibromyalgia: A 13-Week, Randomized, Placebo-Controlled, Crossover Trial

    Science.gov (United States)

    Kim, Jeong Lan; Rele, Shilpa; Marks, David M.; Masand, Prakash S.; Yerramsetty, Pallavi; Millet, Robert A.; Keefe, Richard S.

    2013-01-01

    Objective: To investigate whether milnacipran is safe and effective in improving cognitive function in patients with fibromyalgia. Method: Patients were randomly assigned to receive milnacipran or placebo for 6 weeks, followed by a 1-week washout and then crossover to the other arm for another 6 weeks. The overall trial lasted 13 weeks and was conducted between July 2011 and May 2013. Assessments were performed at each visit. Neurocognition was measured by the Brief Assessment of Cognition (BAC) and MATRICS. Pain was assessed by the visual analog scale (VAS) for pain. Global assessment of fibromyalgia symptoms was measured by the Fibromyalgia Impact Questionnaire (FIQ) and tender point examination. Depression was assessed by the Beck Depression Inventory (BDI). Fatigue was assessed by the Fatigue Severity Scale. Functional outcome was evaluated by the Health Assessment Questionnaire. The Clinical Global Impressions–Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Patients Clinical Global Impression of Change were used to measure the global impression of severity and improvement. Results: 26 subjects were screened, and 20 subjects completed the trial. The change in verbal memory (P = .001) and the composite T score (P = .044) of the BAC and the change in the attention-vigilance domain T score (P = .042) were significantly improved, but there were no differences between the drug and placebo groups. The changes in the CGI-S scores were not significant, but the changes in the Clinical Impression-Improvement (CGI-I) scores showed worsening in the placebo group at week 1 (P = .032), week 2 (P = .024), week 4 (P = .024), and week 6 (P = .60) compared to baseline. The change in FIQ scores was not significant. Conclusions: Milnacipran may have a potential role in the improvement of pain, disability, and mood. The effect of milnacipran on cognition in fibromyalgia needs further research. Trial Registration: ClinicalTrials.gov identifier: NCT01829243 PMID

  3. Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

    Science.gov (United States)

    Quintana, D S; Westlye, L T; Hope, S; Nærland, T; Elvsåshagen, T; Dørum, E; Rustan, Ø; Valstad, M; Rezvaya, L; Lishaugen, H; Stensønes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G; Andreassen, O A

    2017-05-23

    The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η 2 =0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

  4. Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

    Science.gov (United States)

    Holscher, Hannah D; Bauer, Laura L; Gourineni, Vishnupriya; Pelkman, Christine L; Fahey, George C; Swanson, Kelly S

    2015-09-01

    Prebiotics resist digestion, providing fermentable substrates for select gastrointestinal bacteria associated with health and well-being. Agave inulin differs from other inulin type fibers in chemical structure and botanical origin. Preclinical animal research suggests these differences affect bacterial utilization and physiologic outcomes. Thus, research is needed to determine whether these effects translate to healthy adults. We evaluated agave inulin utilization by the gastrointestinal microbiota by measuring fecal fermentative end products and bacterial taxa. A randomized, double-blind, placebo-controlled, 3-period, crossover trial was undertaken in healthy adults (n = 29). Participants consumed 0, 5.0, or 7.5 g agave inulin/d for 21 d with 7-d washouts between periods. Participants recorded daily dietary intake; fecal samples were collected during days 16-20 of each period and were subjected to fermentative end product analysis and 16S Illumina sequencing. Fecal Actinobacteria and Bifidobacterium were enriched (P inulin/d, respectively, compared with control. Desulfovibrio were depleted 40% with agave inulin compared with control. Agave inulin tended (P inulin (g/kcal) and Bifidobacterium (r = 0.41, P inulin/d) per kilocalorie was positively associated with fecal butyrate (r = 0.30, P = 0.005), tended to be positively associated with Bifidobacterium (r = 0.19, P = 0.08), and was negatively correlated with Desulfovibrio abundance (r = -0.31, P = 0.004). Agave inulin supplementation shifted the gastrointestinal microbiota composition and activity in healthy adults. Further investigation is warranted to determine whether the observed changes translate into health benefits in human populations. This trial was registered at clinicaltrials.gov as NCT01925560. © 2015 American Society for Nutrition.

  5. Effect of fibular repositioning taping in adult basketball players with chronic ankle instability: a randomized, placebo-controlled, crossover trial.

    Science.gov (United States)

    Alves, Yanina; Ribeiro, Fernando; Silva, Anabela G

    2017-07-05

    Chronic ankle instability presents a high incidence and prevalence in basketbal players. It's important to develop strategies to reduce the functional and mechanical limitations resulting from this condition. To compare the effect of Mulligan ́s fibular repositioning taping with a placebo taping immediatly after application and after a running test (Yo-Yo IRT). 16 adult basketball players (10 male, 6 female) with chronic ankle instability and mean age 21.50 ± 2.76 years old. Assessment of static postural control (15 seconds of unipedal stance test with eyes closed in a force platform), functional performance (figure 8 hop test and lateral hop test) and neuromuscular control (peroneus longus latency time in sudden inversion) in two conditions: Mulligan and Placebo. No significant effect was found for the intervantion factor in both hop tests (p>0.170), but there was a significant effect for the time factor (p<0.03). For the peroneus longus latency time, there was a significant interaction between factors (p=0.028) and also for time (p=0.042). No significant effect was found for any of the static postural control variables (area, speed and total displacement) (p≥0.10). There was no differences between Mulligan's fibular repositioning taping and Placebo taping in postural control and functional performance in basketball players with chronic ankle instability. However, Mulligan's taping appears to reduce peroneus longus latency time after a running when compared with a placebo taping.

  6. Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9 on the Upper Female Reproductive Tract: A Randomized Crossover Study.

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    Karen Smith-McCune

    Full Text Available Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to the lower-than-expected efficacy of HIV microbicides. Our objective was to study the effects of intravaginal gels on the immune microenvironment of the cervix and uterus. In this randomized crossover study, 27 healthy female volunteers used a nightly application of intravaginal nonoxynol-9 (N9 gel as a "failed" microbicide or the universal placebo gel (UPG as a "safe" gel (intervention cycles, or nothing (control cycle from the end of menses to the mid-luteal phase. At a specific time-point following ovulation, all participants underwent sample collection for measurements of T-cell phenotypes, gene expression, and cytokine/chemokine protein concentrations from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI intervention effects, for N9 and UPG relative to control. Exposure to N9 gel and UPG generated a common "harm signal" that included transcriptional up-regulation of inflammatory genes chemokine (C-C motif ligand 20 (macrophage inflammatory factor-3alpha and interleukin 8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor, and transcriptional up-regulation of inflammatory mediators glycodelin-A and osteopontin in the endometrium. These results need to be replicated with a larger sample, but underscore the need to consider the effects of microbicide agents and gel excipients on the upper female reproductive tract in studies of vaginal microbicides.

  7. A randomized double blind crossover placebo-controlled clinical trial to assess the effects of a mouthwash containing chlorine dioxide on oral malodor

    Directory of Open Access Journals (Sweden)

    Yokoyama Sayaka

    2008-12-01

    Full Text Available Abstract Background Previous research has shown the oxidizing properties and microbiological efficacies of chlorine dioxide (ClO2, however, its clinical efficacies on oral malodor have been evaluated only with organoleptic measurements (OM or sulphide monitors. No clinical studies have investigated the inhibitory effects of ClO2 on volatile sulfur compounds (VSCs using gas chromatography (GC. The aim of this study was to assess the inhibitory effects of a mouthwash containing ClO2 on morning oral malodor using OM and GC. Methods A randomized, double blind, crossover, placebo-controlled clinical trial was conducted among 15 healthy male volunteers, who were divided into 2 groups. In the first test phase, the group 1 subjects (N = 8 were instructed to rinse with the experimental mouthwash containing ClO2, and those in group 2 (N = 7 to rinse with the placebo mouthwash without ClO2. In the second test, phase after a one week washout period, each group used the opposite mouthwash. Oral malodor was evaluated before rinsing, right after rinsing and every 30 minutes up to 4 hours with OM, and concentrations of hydrogen sulfide (H2S, methyl mercaptan (CH3SH and dimethyl sulfide ((CH32S, the main VSCs of human oral malodor, were evaluated with GC. Results The baseline oral condition in the subjects in the 2 groups did not differ significantly. The mouthwash containing ClO2 improved morning bad breath according to OM and reduced concentrations of H2S, CH3SH and (CH32S according to GC up to 4 hours after rinsing. OM scores with ClO2 were significantly lower than those without ClO2 at all examination times. Significant reductions in the concentrations of the three kinds of VSCs measured by GC were also evident at all examination times. The concentrations of the three gases with ClO2 were significantly lower than those without ClO2 at most examination times. Conclusion In this explorative study, ClO2 mouthwash was effective at reducing morning malodor for 4

  8. Bright Light for Weight Loss: Results of a Controlled Crossover Trial

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    Konstantin V. Danilenko

    2013-02-01

    Full Text Available Objective: To investigate whether bright light treatment can reduce body mass in overweight subjects irrespective of their seasonal (= light dependence. Methods: A crossover, placebo-controlled, randomized clinical trial was performed between November and April in Novosibirsk, Russia (55° N. The trial comprised a 3-week in-home session of morning bright light treatment using a device of light-emitting diodes and a 3-week placebo session by means of a deactivated ion generator, separated by an off-protocol period of at least 23 days. The number of placebo and light sessions was matched with respect to season. Data were obtained from 34 overweight women, aged 20-54 years, 10 were seasonal-dependent according to the Seasonal Pattern Assessment Questionnaire. Weekly measures included body weight, percentage body fat by bioimpedancemetry, and subjective scores (appetite, mood, energy levels. Results: Motivation and expectation towards weight loss were similar for the two intervention sessions. With light, compared to the placebo session, weight did not reduce significantly, but percentage fat, fat mass, and appetite were significantly lower (average fat reduction 0.35 kg. The latter two results remained significant after excluding seasonal-dependent subjects from the analysis. Irrespective of the type of intervention, seasonal-dependent subjects had greater weight and fat mass changes during treatment (decline p 0.036 or between sessions (regain p 0.003. Photoperiod (p = 0.0041, air temperature to a lesser extent (p = 0.012, but not sunshine (p = 0.29 was associated with the weight change (greater weight reduction if the second session was in spring. Conclusion: Morning bright light treatment reduces body fat and appetite in overweight women and may be included in weight control programs.

  9. Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial.

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    Elise Mok

    Full Text Available Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD. We evaluated the functional benefit of 4 months oral glutamine in DMD.30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine, markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine, serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage, safety and oral nutrient intake. There was no improvement in the primary end point (walking speed or in secondary measures of muscle function (2-minute walk test, work, power in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.(ClinicalTrials.gov NCT00296621.

  10. Duloxetine inhibits effects of MDMA ("ecstasy" in vitro and in humans in a randomized placebo-controlled laboratory study.

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    Cédric M Hysek

    Full Text Available This study assessed the effects of the serotonin (5-HT and norepinephrine (NE transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.Clinicaltrials.gov NCT00990067.

  11. Clinical trial of modulatory effects of oxytocin treatment on higher-order social cognition in autism spectrum disorder: a randomized, placebo-controlled, double-blind and crossover trial.

    Science.gov (United States)

    Preckel, Katrin; Kanske, Philipp; Singer, Tania; Paulus, Frieder M; Krach, Sören

    2016-09-21

    Autism spectrum disorders are neurodevelopmental conditions with severe impairments in social communication and interaction. Pioneering research suggests that oxytocin can improve motivation, cognition and attention to social cues in patients with autism spectrum disorder. The aim of this clinical trial is to characterize basic mechanisms of action of acute oxytocin treatment on neural levels and to relate these to changes in different levels of socio-affective and -cognitive functioning. This clinical study is a randomized, double-blind, cross-over, placebo-controlled, multicenter functional magnetic resonance imaging study with two arms. A sample of 102 male autism spectrum disorder patients, diagnosed with Infantile Autistic Disorder (F84.0 according to ICD-10), Asperger Syndrome (F84.5 according to ICD-10), or Atypical Autism (F84.1 according to ICD-10) will be recruited and will receive oxytocin and placebo nasal spray on two different days. Autism spectrum disorder patients will be randomized to determine who receives oxytocin on the first and who on the second visit. Healthy control participants will be recruited and case-control matched to the autism spectrum disorder patients. The primary outcome will be neural network activity, measured with functional magnetic resonance imaging while participants perform socio-affective and -cognitive tasks. Behavioral markers such as theory of mind accuracy ratings and response times will be assessed as secondary outcomes in addition to physiological measures such as skin conductance. Trait measures for alexithymia, interpersonal reactivity, and social anxiety will also be evaluated. Additionally, we will analyze the effect of oxytocin receptor gene variants and how these potentially influence the primary and secondary outcome measures. Functional magnetic resonance imaging assessments will take place at two time points which will be scheduled at least two weeks apart to ensure a sufficient wash-out time after oxytocin

  12. Ranolazine versus placebo in patients with ischemic cardiomyopathy and persistent chest pain or dyspnea despite optimal medical and revascularization therapy: randomized, double-blind crossover pilot study

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    Shammas NW

    2015-03-01

    Full Text Available Nicolas W Shammas,1 Gail A Shammas,1 Kathleen Keyes,2 Shawna Duske,1 Ryan Kelly,1 Michael Jerin3 1Midwest Cardiovascular Research Foundation, 2Cardiovascular Medicine, Private Corporation, 3St Ambrose University, Davenport, IA, USA Background: Patients with ischemic cardiomyopathy (ICM may continue to experience persistent chest pain and/or dyspnea despite pharmacologic therapy and revascularization. We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients.Methods: In this randomized, double-blind, crossover-design pilot study, 28 patients with ICM (ejection fraction less or equal 40% were included after providing informed consent. A total of 24 patients completed both placebo and ranolazine treatments and were analyzed. All patients were on treatment with a beta blocker, an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker, and at least one additional antianginal drug. After randomization, patients received up to 1,000 mg ranolazine orally twice a day, as tolerated, versus placebo. The primary end point was change in angina as assessed by the Seattle Angina Questionnaire (SAQ, or in dyspnea as assessed by the Rose Dyspnea Scale (RDS. Change in the RDS and SAQ score from baseline was compared, for ranolazine and placebo, using the Wilcoxon signed rank test or paired t-test.Results: Patients had the following demographic and clinical variables: mean age of 71.5 years; male (82.1%; prior coronary bypass surgery (67.9%; prior coronary percutaneous intervention (85.7%; prior myocardial infarction (82.1%; diabetes (67.9%; and mean ejection fraction of 33.1%. No statistical difference was seen between baseline RDS score and that after placebo or ranolazine (n=20 (P≥0.05. There was however, an improvement in anginal frequency (8/10 patients (P=0.058, quality of life (8/10 patients (P=0.048, and mean score of all components of the SAQ questionnaire (n=10 (P=0.047 with ranolazine

  13. Effect of high-dose growth hormone and glutamine on body composition, urine creatinine excretion, fatty acid absorption, and essential fatty acids status in short bowel patients - A randomized, double-blind, crossover, placebo-controlled study

    DEFF Research Database (Denmark)

    Jeppesen, P.B.; Szkudlarek, J.; Høy, Carl-Erik

    2001-01-01

    Background: Positive effects of high dose growth hormone and glutamine (GH+GLN) on body composition in short bowel patients have been described. Lack of effects on intestinal absorption found in some studies has been ascribed to concomitant essential fatty acid (EFA) deficiency. This study...... describes changes in body weight (BW) and composition, 24-h urine creatinine excretion, intestinal fatty acid absorption (total, saturated, unsaturated and EFA), and EFA status in relation to treatment with GH+GLN in s short bowel patients. Methods: A double-blind, crossover study between placebo and growth...... with baseline. Twenty-four-hour urine creatinine excretion did not differ between study periods. No changes in intestinal absorption of fatty acids were seen, and no changes in EFAs measured in plasma phospholipids were observed. Only 1 of 8 patients, who did not receive parenteral lipids, had a Holman index...

  14. Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

    Science.gov (United States)

    Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

    2017-07-01

    Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological

  15. Acute Effects of Nitrate-Rich Beetroot Juice on Blood Pressure, Hemostasis and Vascular Inflammation Markers in Healthy Older Adults: A Randomized, Placebo-Controlled Crossover Study

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    Kyle Raubenheimer

    2017-11-01

    Full Text Available Aging is associated with a vasoconstrictive, pro-coagulant, and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide. Dietary nitrate elicits vasodilatory, anti-coagulant and anti-inflammatory effects in younger individuals, but little is known about whether these benefits are evident in older adults. We investigated the effects of 140 mL of nitrate-rich (HI-NI; containing 12.9 mmol nitrate versus nitrate-depleted beetroot juice (LO-NI; containing ≤0.04 mmol nitrate on blood pressure, blood coagulation, vascular inflammation markers, plasma nitrate and nitrite before, and 3 h and 6 h after ingestion in healthy older adults (five males, seven females, mean age: 64 years, age range: 57–71 years in a randomized, placebo-controlled, crossover study. Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion (p < 0.05. Systolic, diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only (p < 0.05. The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake (p < 0.05, indicating reduced platelet activation. The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake (p < 0.05, suggesting a shift toward an anti-adhesive granulocyte phenotype. Numbers of blood CD14++CD16+ intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion (p < 0.05, but the clinical implications of this response are currently unclear. These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets. Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging.

  16. A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

    Science.gov (United States)

    2012-01-01

    Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

  17. Effects of sodium and potassium supplementation on blood pressure and arterial stiffness: a fully controlled dietary intervention study

    NARCIS (Netherlands)

    Gijsbers, L.; Dower, J.I.; Mensink, M.R.; Siebelink, A.E.; Bakker, S.J.L.; Geleijnse, J.M.

    2015-01-01

    We performed a randomised, placebo-controlled, crossover study to examine the effects of sodium and potassium supplementation on blood pressure (BP) and arterial stiffness in untreated (pre)hypertensive individuals. During the study, subjects were on a fully controlled diet that was relatively low

  18. Effect of an herbal/botanical supplement on recovery from delayed onset muscle soreness: a randomized placebo-controlled trial.

    Science.gov (United States)

    Rynders, Corey A; Weltman, Judy Y; Rynders, Sara D; Patrie, James; McKnight, John; Katch, Frank I; Hertel, Jay; Weltman, Arthur

    2014-01-01

    We examined the effects of a proprietary herbal/botanical supplement (StemSport, Stemtech, San Clemente, CA.) suggested to increase circulating stem cells, decrease inflammation, and attenuate exercise induced muscle damage on recovery from delayed onset muscle soreness (DOMS). Sixteen subjects (male = 7, female = 9; age 23.8 ± 10 years; height 171.9 ± 10 cm, mass 72.2 ± 15 kg) were randomized in a crossover, double-blind, placebo controlled trial to receive a placebo or StemSport supplement (6150 mg/day) for 14 days. DOMS was induced on day 7 for both placebo and active conditions in the non-dominant elbow flexor group with repeated eccentric repetitions. Muscle swelling (biceps girth), elbow flexor isometric strength (hand held dynamometer), muscle pain/tenderness (visual analog scale), range of motion (active elbow flexion and extension), and inflammation (hsCRP, IL6, and TNF-α) were measured at baseline and at 24 h, 48 h, 72 h, and 168 h (1 week) post eccentric exercise. The crossover washout period was ≥14 days. No significant condition-by-time interactions between placebo and StemSport supplementation were observed with regard to measures of pain (p = 0.59), tenderness (p = 0.71), isometric strength (p = 0.32), elbow flexion (p = 0.45), muscle swelling (p = 0.90), or inflammation (p > 0.90). Decrements in elbow extension range of motion 48 h post-exercise were less after StemSport supplementation (Δ elbow extension 48 h post; StemSport, -2.0 deg; placebo, -10 deg; p = 0.003). These data suggest that compared to placebo, StemSport supplementation does not improve outcome measures related to muscle recovery after acute upper-arm induced DOMS.

  19. ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.

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    Marco Barchi

    2008-05-01

    Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.

  20. Diagnostic value of lumbar facet joint injection: a prospective triple cross-over study.

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    Uwe Schütz

    Full Text Available The diagnosis "lumbar facet syndrome" is common and often indicates severe lumbar spine surgery procedures. It is doubtful whether a painful facet joint (FJ can be identified by a single FJ block. The aim of this study was to clarify the validity of a single and placebo controlled bilateral FJ blocks using local anesthetics. A prospective single blinded triple cross-over study was performed. 60 patients (31 f, 29 m, mean age 53.2 yrs (22-73 with chronic low back pain (mean pain persistance 31 months, 6 months of conservative treatment without success admitted to a local orthopaedic department for surgical or conservative therapy of chronic LBP, were included in the study. Effect on pain reduction (10 point rating scale was measured. The 60 subjects were divided into six groups with three defined sequences of fluoroscopically guided bilateral monosegmental lumbar FJ test injections in "oblique needle" technique: verum-(local anaesthetic-, placebo-(sodium chloride- and sham-injection. Carry-over and periodic effects were evaluated and a descriptive and statistical analysis regarding the effectiveness, difference and equality of the FJ injections and the different responses was performed. The results show a high rate of non-response, which documents the lack of reliable and valid predictors for a positive response towards FJ blocks. There was a high rate of placebo reactions noted, including subjects who previously or later reacted positively to verum injections. Equivalence was shown among verum vs. placebo and partly vs. sham also. With regard to test validity criteria, a single intraarticular FJ block with local anesthetics is not useful to detect the pain-responsible FJ and therefore is no valid and reliable diagostic tool to specify indication of lumbar spine surgery. Comparative FJ blocks with local anesthetics and placebo-controls have to be interpretated carefully also, because they solely give no proper diagnosis on FJ being main pain

  1. Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.

    Science.gov (United States)

    Miner, Philip B; Silberg, Debra G; Ruth, Magnus; Miller, Frank; Pandolfino, John

    2014-11-18

    The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders. In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance-pH measurements were taken. Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. ClinicalTrials.gov identifier: NCT01043185.

  2. A brief history of placebos and clinical trials in psychiatry.

    Science.gov (United States)

    Shorter, Edward

    2011-04-01

    The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

  3. Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

    Science.gov (United States)

    Nicola, Valentina G.; Vischer, Nerina; Donzelli, Massimiliano; Krähenbühl, Stephan; Grouzmann, Eric; Huwyler, Jörg; Hoener, Marius C.; Liechti, Matthias E.

    2012-01-01

    This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence. Trial Registration Clinicaltrials.gov NCT00990067 PMID:22574166

  4. Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study

    Directory of Open Access Journals (Sweden)

    Goldstein Brahm

    2012-01-01

    Full Text Available Abstract Background Effects of nitric oxide (NO on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control. Patients/Methods Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals. Results Activated clotting time (ACT, prothrombin time (PT and activated partial thromboplastin time (aPTT increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11 and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12. Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group. Conclusions Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

  5. A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects.

    Science.gov (United States)

    Hug, Bruce; Abbas, Richat; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

    2010-08-01

    Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were neratinib. Pharmacokinetic/pharmacodynamic analysis revealed no relationship between neratinib concentrations and QTc interval. No subjects had QTcI, QTcF, or QTcN intervals >450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P neratinib do not prolong the QTc interval in healthy subjects. (c) 2010 AACR.

  6. Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Micka, Antje; Siepelmeyer, Anne; Holz, Anja; Theis, Stephan; Schön, Christiane

    2017-02-01

    Constipation is among the most common health impairments in Western countries. This study aimed to determine the effect of the chicory-derived fermentable dietary fiber Orafti ® Inulin on stool frequency in healthy subjects with constipation. The study was conducted according to recent guidance documents for investigating bowel function and used a randomized, double-blind, placebo-controlled, cross-over design with a 2-week wash-out phase. Each study period comprised a run-in phase followed by 4 weeks daily intake of 3 × 4g inulin or maltodextrin (placebo). Forty-four healthy volunteers with constipation documented stool frequency and consistency, gastrointestinal characteristics and quality of life. Consumption of Orafti ® Inulin significantly increased stool frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0] stools/week, p = 0.038). This was accompanied by a softening of stools and trend toward higher satisfaction versus placebo (p = 0.059). In conclusion, Orafti ® Inulin was effective in volunteers with chronic constipation and significantly improved bowel function. This trial was registered at clinicaltrials.gov as NCT02548247.

  7. Magnet therapy for the relief of pain and inflammation in rheumatoid arthritis (CAMBRA: A randomised placebo-controlled crossover trial

    Directory of Open Access Journals (Sweden)

    Richmond Stewart J

    2008-09-01

    Full Text Available Abstract Background Rheumatoid arthritis is a common inflammatory autoimmune disease. Although disease activity may be managed effectively with prescription drugs, unproven treatments such as magnet therapy are sometimes used as an adjunct for pain control. Therapeutic devices incorporating permanent magnets are widely available and easy to use. Magnets may also be perceived as a more natural and less harmful alternative to analgesic compounds. Of interest to health service researchers is the possibility that magnet therapy might help to reduce the economic burden of managing chronic musculoskeletal disorders. Magnets are extremely cheap to manufacture and prolonged treatment involves a single cost. Despite this, good quality scientific evidence concerning the safety, effectiveness and cost-effectiveness of magnet therapy is scarce. The primary aim of the CAMBRA trial is to investigate the effectiveness of magnet therapy for relieving pain and inflammation in rheumatoid arthritis. Methods/Design The CAMBRA trial employs a randomised double-blind placebo-controlled crossover design. Participant will each wear four devices: a commercially available magnetic wrist strap; an attenuated wrist strap; a demagnetised wrist strap; and a copper bracelet. Device will be allocated in a randomised sequence and each worn for five weeks. The four treatment phases will be separated by wash out periods lasting one week. Both participants and researchers will be blind, as far as feasible, to the allocation of experimental and control devices. In total 69 participants will be recruited from general practices within the UK. Eligible patients will have a verified diagnosis of rheumatoid arthritis that is being managed using drugs, and will be experiencing chronic pain. Outcomes measured will include pain, inflammation, disease activity, physical function, medication use, affect, and health related costs. Data will be collected using questionnaires, diaries, manual

  8. Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

    Science.gov (United States)

    Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

    2016-01-01

    Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

  9. Effect of Alpinia galanga on Mental Alertness and Sustained Attention With or Without Caffeine: A Randomized Placebo-Controlled Study.

    Science.gov (United States)

    Srivastava, Shalini; Mennemeier, Mark; Pimple, Surekha

    2017-01-01

    Although Alpinia galanga has been reported to improve cognitive performance in animals, it has not been thoroughly studied for its potential psychostimulant effect in humans. A randomized, double-dummy, double-blind, placebo-controlled cross-over study was conducted to determine the effect of A galanga on mental alertness and sustained attention in comparison with caffeine and placebo in participants with a habitual caffeine intake. Fifty-nine participants (18-40 years and body mass index of ≥18.5 and caffeine consumption were enrolled. The participants had a Generalized Anxiety Disorder-7 score ≤7, Patient Health Questionnaire-9 score ≤14 and a Jin Fan's Attention Network Test alertness score of 50 ± 20 ms. The interventional product (placebo, A galanga proprietary extract [E-AG-01], caffeine, and a combination of E-AG-01 with caffeine) was administered to the participants, followed by sequential administration of the remaining interventions on the consecutive study visits; the effects on mental alertness, sustained attention, and sleep architecture, along with safety and tolerability, were analyzed by validated methods. In the E-AG-01 group, the alertness score was increased by 11.65 ± 23.94, 12.50 ± 19.73, and 12.62 ± 0.68 ms from baseline at 1, 3 (p = 0.042), and 5 hours, respectively, indicating its efficacy to enhance mental alertness and the increase in alertness score as compared to placebo. In the composite group (E-AG-01 with caffeine), mean response time was significantly reduced, by 15.55 ms (p = 0.026) at 3 hours. A galanga (E-AG-01) induces a beneficial effect in mental alertness and the combination of A galanga with caffeine impedes the caffeine crash and improves sustained attention at 3 hours. Thus, these stimulant effects might yield a new usage for A galanga as a key ingredient in energy drinks or similar products.

  10. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Ito Mikako

    2011-10-01

    Full Text Available Abstract Background Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented. Methods We performed open-label trial of drinking 1.0 liter per day of hydrogen-enriched water for 12 weeks in five patients with progressive muscular dystrophy (PMD, four patients with polymyositis/dermatomyositis (PM/DM, and five patients with mitochondrial myopathies (MM, and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks. We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with DM and 12 patients with MM, and measured 18 serum parameters every 4 weeks. Results In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in PMD and MM, fasting blood glucose in PMD, serum matrix metalloproteinase-3 (MMP3 in PM/DM, and serum triglycerides in PM/DM. In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in MM. Lactate-to-pyruvate ratios in MM and MMP3 in DM also exhibited favorable responses but without statistical significance. No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin

  11. "Live high-train low" using normobaric hypoxia: a double-blinded, placebo-controlled study

    DEFF Research Database (Denmark)

    Siebenmann, Christoph; Robach, Paul; Jacobs, Robert A

    2012-01-01

    The combination of living at altitude and training near sea level [live high-train low (LHTL)] may improve performance of endurance athletes. However, to date, no study can rule out a potential placebo effect as at least part of the explanation, especially for performance measures. With the use o...... of a placebo-controlled, double-blinded design, we tested the hypothesis that LHTL-related improvements in endurance performance are mediated through physiological mechanisms and not through a placebo effect. Sixteen endurance cyclists trained for 8 wk at low altitude (...

  12. Electric field-navigated transcranial magnetic stimulation for chronic tinnitus: a randomized, placebo-controlled study.

    Science.gov (United States)

    Sahlsten, Hanna; Virtanen, Juuso; Joutsa, Juho; Niinivirta-Joutsa, Katri; Löyttyniemi, Eliisa; Johansson, Reijo; Paavola, Janika; Taiminen, Tero; Sjösten, Noora; Salonen, Jaakko; Holm, Anu; Rauhala, Esa; Jääskeläinen, Satu K

    2017-09-01

    Repetitive transcranial magnetic stimulation (rTMS) may alleviate tinnitus. We evaluated effects of electric field (E-field) navigated rTMS targeted according to tinnitus pitch. No controlled studies have investigated anatomically accurate E-field-rTMS for tinnitus. Effects of E-field-rTMS were evaluated in a prospective randomised placebo-controlled 6-month follow-up study on parallel groups. Patients received 10 sessions of 1 Hz rTMS or placebo targeted to the left auditory cortex corresponding to tonotopic representation of tinnitus pitch. Effects were evaluated immediately after treatment and at 1, 3 and 6 months. Primary outcome measures were visual analogue scores (VAS 0-100) for tinnitus intensity, annoyance and distress, and the Tinnitus Handicap Inventory (THI). Thirty-nine patients (mean age 50.3 years). The mean tinnitus intensity (F 3  = 15.7, p tinnitus, differences between active and placebo groups remained non-significant, due to large placebo-effect and wide inter-individual variation.

  13. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects.

    Science.gov (United States)

    Costabile, Adele; Kolida, Sofia; Klinder, Annett; Gietl, Eva; Bäuerlein, Michael; Frohberg, Claus; Landschütze, Volker; Gibson, Glenn R

    2010-10-01

    There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides-Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed. There were no adverse gastrointestinal symptoms apart from a significant increase in mild and moderate bloating upon VLCI ingestion. These observations were also confirmed by in vitro gas production measurements. In conclusion, daily consumption of VLCI extracted from globe artichoke exerted a pronounced prebiotic effect on the human faecal microbiota composition and was well tolerated by all volunteers.

  14. Actual driving performance and psychomotor function in healthy subjects after acute and subchronic treatment with escitalopram, mirtazapine, and placebo: a crossover trial.

    Science.gov (United States)

    Wingen, Marleen; Bothmer, John; Langer, Stefan; Ramaekers, Johannes G

    2005-04-01

    The effects of escitalopram 10 to 20 mg/day and mirtazapine 30 to 45 mg/day on actual driving and psychomotor performance of 18 healthy subjects were determined in a randomized, double-blind, placebo-controlled, multiple-dose, 3-way crossover trial. Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Subjects received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16, reflecting acute period, dose increase, and steady state, respectively, the Road Tracking Test was performed. The main parameter was standard deviation of lateral position. Psychomotor performance was also assessed on days 2, 9, and 16 by laboratory computer tasks. Subjective sleep quality was measured with the Groninger Sleep Quality Scale, and mood was measured by visual analogue scales. Treatment differences were apparent during the acute treatment period, in which subjects treated with mirtazapine 30 mg performed less well on the driving test as compared to placebo. The Divided Attention Task results also revealed a significant increase in tracking error after a single dose of mirtazapine 30 mg as compared to placebo. Mirtazapine decreased feelings of alertness and contentedness. Mirtazapine did not affect performance on days 9 and 16 of treatment. Escitalopram did not affect driving, psychomotor performance, or subjective mood throughout treatment. Driving performance, as well as psychomotor functioning, was not affected by escitalopram treatment in healthy subjects. Driving performance was significantly impaired after ingestion of mirtazapine 30 mg during the acute treatment period.

  15. Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials.

    Science.gov (United States)

    Cohen, Stephanie C; Mulqueen, Jilian M; Ferracioli-Oda, Eduardo; Stuckelman, Zachary D; Coughlin, Catherine G; Leckman, James F; Bloch, Michael H

    2015-09-01

    Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics. We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant

  16. A randomised, double-blind, placebo controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread in healthy volunteers.

    Science.gov (United States)

    Walton, Gemma E; Lu, Congyi; Trogh, Isabel; Arnaut, Filip; Gibson, Glenn R

    2012-06-01

    Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS) at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS) compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA) levels in saliva were also measured. Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated.

  17. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

    Science.gov (United States)

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E230 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (PMaca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

  18. Increased eating control and energy levels associated with consumption of bitter orange (p-synephrine extract: a randomized placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Kaats GR

    2017-07-01

    Full Text Available Gilbert R Kaats,1 Robert B Leckie,2 Nate Mrvichin,1 Sidney J Stohs3 1Integrative Health Technologies, Inc., 2R.B. Leckie Research Consultants, San Antonio, TX, 3Creighton University Medical Center, Omaha, NE, USA Abstract: Using a placebo-controlled double-blinded 30-day protocol, 40 overweight adults were asked to consume a chocolate-flavored chew 15–30 min before their two largest meals of the day. The chews contained either a placebo or an “active” product (100 mg of a bitter orange extract, standardized to 51.5 mg p-synephrine. Subjects completed a 13-item Weight Control Support Scale (WCSS containing eating control, energy level, and palatability subscales daily throughout the study. All 40 subjects completed the study. No adverse effects were reported in either the placebo or active groups. As compared to placebo, subjects consuming the active product reported statistically more (p≤0.001 positive responses on the WCSS as well as on each of the three subscales. This study suggests that, as compared to a placebo control, consuming a chew containing bitter orange extract (51.5 mg p-synephrine 15–30 min before the two largest meals of the day resulted in a statistically significant greater and more positive response to eating/appetite control and a weight-control support scale. Keywords: bitter orange extract, p-synephrine, Citrus aurantium, appetite suppression, energy, safety

  19. Randomized, Double-Blind, Crossover Trial of Amitriptyline for Analgesia in Painful HIV-Associated Sensory Neuropathy.

    Directory of Open Access Journals (Sweden)

    Natalya Dinat

    Full Text Available We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i antiretroviral drug naive individuals, and ii antiretroviral drug users. 124 HIV-infected participants (antiretroviral drug naive = 62, antiretroviral drug users = 62 who met the study criteria for painful HIV-associated sensory neuropathy were randomized to once-daily oral amitriptyline (titrated to a median: interquartile range of 50: 25-50 mg or placebo for six weeks, followed by a three-week washout period and subsequent treatment crossover. The primary outcome measure was change from baseline in worst pain intensity of the feet (measured by participant self-report using an 11-point numerical pain rating scale after six weeks of treatment. 122 of 124 participants completed all study visits and were included in the analysis of the primary outcome. In the antiretroviral drug-naive group (n = 61 there was no significant difference in the mean change in pain score from baseline after six weeks of treatment with placebo or amitriptyline [amitriptyline: 2.8 (SD 3.3 vs. placebo: 2.8 (3.4]. Similarly, there was no significant difference in the change in pain score after six weeks of treatment with placebo or amitriptyline in the antiretroviral drug-user group (n = 61 [amitriptyline: 2.7 (3.3 vs. placebo: 2.1 (2.8]. Controlling for period effects and treatment order effects did not alter the outcome of the analyses. Nor did analyzing the intention-to-treat cohort (missing data interpolated using baseline observation carried forward alter the outcome of the analyses. In summary, amitriptyline, at the doses used here, was no more effective than an inactive placebo at reducing pain intensity in individuals with painful HIV-associated sensory neuropathy of moderate to severe intensity, irrespective of

  20. Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study.

    Science.gov (United States)

    Clayton, Anita H; Croft, Harry A; Yuan, James; Brown, Louise; Kissling, Robert

    2018-01-01

    Depression is often associated with sexual dysfunction, and pharmacologic treatment for hypoactive sexual desire disorder can be considered in women receiving treatment for depression. To evaluate the safety of flibanserin in women treated for depression with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. In this double-blinded, randomized, placebo-controlled trial, women with remitted or mild depression treated with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors who were not postmenopausal and were experiencing symptoms of hypoactive sexual desire disorder (ie, decreased sexual desire and related distress) received flibanserin 50 mg at bedtime (qhs) for 2 weeks and up-titrated to 100 mg qhs, flibanserin 100 mg qhs for the entire treatment period, or placebo for up to 12 weeks. Safety assessment included adverse events and symptoms of depression and anxiety. 73 patients were randomly assigned to flibanserin (both dose groups combined) and 38 to placebo. The sponsor terminated the study early at discontinuation of the development of flibanserin. Treatment duration was at least 8 weeks for 84.9% and 94.7% of patients in the flibanserin and placebo groups, respectively. The most common adverse events (incidence ≥ 2% in the flibanserin group and higher than that in the placebo group) included dry mouth (5.5% for flibanserin vs 2.6% for placebo), insomnia (5.5% vs 2.6%), back pain (4.1% vs 2.6%), and dizziness (4.1% vs 0.0%). There were no serious adverse events and no instances of suicidal ideation or behavior. The proportions of patients with symptom worsening in the flibanserin and placebo groups, respectively, were 6.9% and 21.6% for depression and 1.4% and 2.7% for anxiety. Remission of depression at study end point, as measured by the Quick Inventory of Depressive Symptomatology-Self Report, was experienced by 19.4% of flibanserin-treated patients and 10.8% of patients

  1. The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model- A Randomized, Placebo-Controlled Trial

    DEFF Research Database (Denmark)

    Larsen, Isabelle M; Drewes, Asbjørn M; Olesen, Anne E

    2018-01-01

    should be low. We hypothesized that anti-allodynic and anti-hyperalgesic effects of Diclometh could be demonstrated in a human experimental pain model, and that Diclometh would be safe to administer. Thus, the aims were: 1) To compare two doses of Diclometh versus placebo; 2) To assess the safety profile...... of Diclometh. The study was a cross-over, randomized, double-blind, placebo-controlled comparison of two doses of Diclometh gel (0.1% and 0.2%) administered topically in healthy participants. Nerve growth factor (NGF) and capsaicin intradermal injections were used as human pain models. Pressure stimulation...... of anti-allodynic effect of Diclometh 0.2% was found. Additionally, it was demonstrated that Diclometh was safe to use. This article is protected by copyright. All rights reserved....

  2. Effects of Dietary Supplementation of Astaxanthin and Sesamin on Daily Fatigue: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study

    Directory of Open Access Journals (Sweden)

    Ayano Imai

    2018-02-01

    Full Text Available Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS, strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively. Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people.

  3. Is TENS purely a placebo effect? A controlled study on chronic low back pain.

    Science.gov (United States)

    Marchand, S; Charest, J; Li, J; Chenard, J R; Lavignolle, B; Laurencelle, L

    1993-07-01

    Although high-frequency low-intensity transcutaneous electric nerve stimulation (TENS) has been extensively used to relieve low back pain, experimental studies of its effectiveness have yielded contradictory findings mainly due to methodological problems in pain evaluation and placebo control. In the present study, separate visual analog scales (VAS) were used to measure the sensory-discriminative and motivational-affective components of low back pain. Forty-two subjects were randomly assigned to 1 of 3 groups: TENS, placebo-TENS, and no treatment (control). In order to measure the short-term effect of TENS, VAS pain ratings were taken before and after each treatment session. Also, to measure long-term effects, patients rated their pain at home every 2 h throughout a 3-day period before and 1 week, 3 months and 6 months after the treatment sessions. In comparing the pain evaluations made immediately before and after each treatment session, TENS and placebo-TENS significantly reduced both the intensity and unpleasantness of chronic low back pain. TENS was significantly more efficient than placebo-TENS in reducing pain intensity but not pain unpleasantness. TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness. This additive effect was not found for placebo-TENS. When evaluated at home, pain intensity was significantly reduced more by TENS than placebo-TENS 1 week after the end of treatment, but not 3 months and 6 months later. At home evaluation of pain unpleasantness in the TENS group was never different from the placebo-TENS group.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. 1% hydrocortisone ointment is an effective treatment of pruritus ani: a pilot randomized controlled crossover trial.

    Science.gov (United States)

    Al-Ghnaniem, R; Short, K; Pullen, A; Fuller, L C; Rennie, J A; Leather, A J M

    2007-12-01

    Pruritus ani (PA) is a common condition which is difficult to treat in the absence of obvious predisposing factors. There is paucity of evidence-based guidelines on the treatment of this condition. We examined whether 1% hydrocortisone ointment is an effective treatment for PA. A pilot randomized, double-blind, placebo-controlled, crossover trial was carried out. Eleven patients consented to take part in the trial and ten completed the study. After a 2-week run-in period, patients with primary PA were randomly allocated to receive 1% hydrocortisone ointment or placebo for 2 weeks followed by the opposite treatment for a further 2-week period. There was a washout period of 2 weeks between treatments. The primary outcome measure was reduction in itch using a visual analogue score (VAS). The secondary outcome measures were improvement in quality of life measured using a validated questionnaire (Dermatology Life Quality Index, DLQI) and improvement in clinical appearance of the perianal skin using the Eczema Area and Severity Index (EASI) score. Treatment with 1% hydrocortisone ointment resulted in a 68% reduction in VAS compared with placebo (P=0.019), a 75% reduction in DLQI score (P=0.067), and 81% reduction in EASI score (P=0.01). A short course of mild steroid ointment is an effective treatment for PA.

  5. A randomised, double-blind, placebo controlled cross-over study to determine the gastrointestinal effects of consumption of arabinoxylan-oligosaccharides enriched bread in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Walton Gemma E

    2012-06-01

    Full Text Available Abstract Background Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. Methods A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA levels in saliva were also measured. Results Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. Conclusions AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated.

  6. Memantine for prophylaxis of chronic tension-type headache--a double-blind, randomized, crossover clinical trial

    DEFF Research Database (Denmark)

    Lindelof, K; Bendtsen, L; Lindelof, K

    2009-01-01

    Treatment for chronic tension-type headache (CTTH) is unsatisfactory. Our aim was to investigate the efficacy of the N-methyl D-aspartate (NMDA) antagonist memantine in the prophylactic treatment of CTTH. We included 40 patients in a randomized, double-blind, placebo-controlled, crossover trial....... Memantine 20-40 mg/day or placebo was each given for 10 weeks separated by a 2-week wash-out period; 29 patients completed the study. The primary efficacy variable, area-under-the-headache curve (duration x intensity), did not differ between memantine (1352 +/- 927) and placebo (1449 +/- 976; P = 0.......10). Headache intensity in both sexes was significantly lower on a 0-10 verbal rating scale with memantine (3.8) than with placebo (4.1; P = 0.03). In women, area-under-the-headache curve was significantly lower with memantine (1343 +/- 919) than with placebo (1555 +/- 1019; P = 0.01). The most common side...

  7. Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study

    Directory of Open Access Journals (Sweden)

    Galpin Andrew J

    2009-08-01

    Full Text Available Abstract Background The purpose of the present investigation was to determine the effects of EPA/DHA supplementation on resting and exercise-induced inflammation and oxidative stress in exercise-trained men. Fourteen men supplemented with 2224 mg EPA+2208 mg DHA and a placebo for 6 weeks in a random order, double blind cross-over design (with an 8 week washout prior to performing a 60 minute treadmill climb using a weighted pack. Blood was collected pre and post exercise and analyzed for a variety of oxidative stress and inflammatory biomarkers. Blood lactate, muscle soreness, and creatine kinase activity were also measured. Results Treatment with EPA/DHA resulted in a significant increase in blood levels of both EPA (18 ± 2 μmol·L-1 vs. 143 ± 23 μmol·L-1; p -1 vs. 157 ± 13 μmol·L-1; p 0.05. There was a mild increase in oxidative stress in response to exercise (XO and H2O2 (p Conclusion EPA/DHA supplementation increases blood levels of these fatty acids and results in decreased resting levels of inflammatory biomarkers in exercise-trained men, but does not appear necessary for exercise-induced attenuation in either inflammation or oxidative stress. This may be due to the finding that trained men exhibit a minimal increase in both inflammation and oxidative stress in response to moderate duration (60 minute aerobic exercise.

  8. Effects of sodium and potassium supplementation on endothelial function: a fully controlled dietary intervention study

    NARCIS (Netherlands)

    Gijsbers, L.; Dower, J.I.; Schalkwijk, C.G.; Kusters, Y.H.A.M.; Bakker, S.J.A.; Hollman, P.C.H.; Geleijnse, J.M.

    2015-01-01

    High Na and low K intakes have adverse effects on blood pressure, which increases the risk for CVD. The role of endothelial dysfunction and inflammation in this pathophysiological process is not yet clear. In a randomised placebo-controlled cross-over study in untreated (pre)hypertensives, we

  9. A double-masked, placebo-controlled study of fluoxetine for hypochondriasis.

    Science.gov (United States)

    Fallon, Brian A; Petkova, Eva; Skritskaya, Natalia; Sanchez-Lacay, Arturo; Schneier, Franklin; Vermes, Donna; Cheng, Jianfeng; Liebowitz, Michael R

    2008-12-01

    This study assessed the efficacy, durability, and tolerability of fluoxetine for hypochondriasis, a disorder for which controlled pharmacological trials are scarce. Fifty-seven patients with hypochondriasis were enrolled: 12 discontinued during the placebo run-in, and 45 were randomized to either fluoxetine or placebo for 12 weeks (acute treatment). Responder status was defined as a Clinical Global Impression rating for hypochondriasis of much or very much improved. Secondary outcome measures included severity of hypochondriasis, somatization, anxiety, and depression. Responders to acute treatment entered a 12-week maintenance phase to week 24. Sustained responders at week 24 entered a 12-week double-masked discontinuation phase. Primary analysis used the intent-to-treat sample. More patients responded with improvement in hypochondriasis when given fluoxetine compared with placebo, starting at week 8 (50.0% vs 19.0%, P = 0.03) and continuing to week 12 (62.5% vs 33.3%, P = 0.05). Mean dose at week 12 dose was 51.4 mg (SD, +/-23 mg). The acute treatment response was maintained to week 24 with more responders in the fluoxetine compared with the placebo group (54.2% vs 23.8%, P = 0.04). Significant improvement was not noted on the continuous secondary outcomes measures of hypochondriasis, with the exception of the Clinical Global Impression hypochondriasis severity scale at week 24. Likelihood of response was not associated with severity of psychiatric comorbidity. Durability of response after controlled drug discontinuation could not be reasonably assessed, given the small sample size of patients who entered the discontinuation phase (n = 10). Fluoxetine was well tolerated, with no significant differences in discontinuation due to side effects between treatment groups. Fluoxetine is a moderately effective and well-tolerated treatment for hypochondriasis.

  10. [Placebo-controlled trials in schizophrenia].

    Science.gov (United States)

    Melamed, Yuval; Davidson, Michael; Bleich, Avi

    2004-03-01

    Clinical trials involving human subjects give rise to ethical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective medications or to placebo. The complexity of the problem increases when dealing with mentally ill patients, for whom, on the one hand there is no known cure for their disease, and on the other hand, it is sometimes questionable whether or not they are able to provide informed consent to participate in clinical trials. The Israel Psychiatric Association decided to develop a position paper on the subject of placebo-controlled clinical trials in schizophrenia patients. Discussion groups were established, and the available material in the professional literature was examined, with an emphasis on recent developments. The Declaration of Helsinki and its amendments were analyzed, and experts in the field were consulted. Clinical drug trials for development of new medications are essential in all fields of medicine, especially in psychiatry. The requirement for a placebo arm in pharmaceutical trials presents ethical and clinical dilemmas that are especially complicated with regard to mentally ill persons whose free choice and ability to provide informed consent may be questionable. However, we do not believe that this predicament justifies unconditional rejection of placebo use in psychiatry, when it may provide substantial benefit for some patients. Simultaneously, it is our duty to provide stringent restrictions that will enable strict supervision over the scientific, clinical and ethical aspects of the trials. We propose the following criteria for approval of pharmaceutical trials that include a placebo arm: scientific justification; clinical and ethical justification; provision of informed consent; recruitment of patients hospitalized voluntarily; prevention of harm; administration of additional potential therapeutic interventions; benefit to patients participating in the study; control and follow

  11. Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial.

    Science.gov (United States)

    Hohlfeld, Jens M; Vogel-Claussen, Jens; Biller, Heike; Berliner, Dominik; Berschneider, Korbinian; Tillmann, Hanns-Christian; Hiltl, Simone; Bauersachs, Johann; Welte, Tobias

    2018-02-21

    Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA-inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic. Eligible participants were patients aged at least 40 years with COPD, pulmonary hyperinflation (defined by a baseline residual volume >135% of predicted), a smoking history of at least ten pack-years, and airflow limitation (FEV 1 <80% predicted and post-bronchodilator FEV 1 : forced vital capacity <0·7). Patients with stable cardiovascular disease were eligible, but those with arrhythmias, heart failure, unstable ischaemic heart disease, or uncontrolled hypertension were not. We randomly assigned participants (1:1) to either receive a combined inhaled dual bronchodilator containing the LABA indacaterol (110 μg as maleate salt) plus the LAMA glycopyrronium (50 μg as bromide salt) once per day for 14 days, followed by a 14-day washout, then a matched placebo for 14 days, or to receive the same treatments in reverse order. The randomisation was done using lists and was concealed from patients and investigators. The primary endpoint was the effect of indacaterol-glycopyrronium versus placebo on left-ventricular end-diastolic volume measured by MRI done on day 1 (visit 4) and day 15 (visit 5) in treatment period 1 and on day 29 (visit 6) and day 43 (visit 7) in treatment period 2 in the per-protocol population. Left-ventricular end-diastolic volume was indexed to body surface area. Safety was assessed in all participants who received

  12. A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

    Science.gov (United States)

    Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

    2014-12-01

    The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

  13. A Case Study of Controlling Crossover in a Selection Hyper-heuristic Framework Using the Multidimensional Knapsack Problem.

    Science.gov (United States)

    Drake, John H; Özcan, Ender; Burke, Edmund K

    2016-01-01

    Hyper-heuristics are high-level methodologies for solving complex problems that operate on a search space of heuristics. In a selection hyper-heuristic framework, a heuristic is chosen from an existing set of low-level heuristics and applied to the current solution to produce a new solution at each point in the search. The use of crossover low-level heuristics is possible in an increasing number of general-purpose hyper-heuristic tools such as HyFlex and Hyperion. However, little work has been undertaken to assess how best to utilise it. Since a single-point search hyper-heuristic operates on a single candidate solution, and two candidate solutions are required for crossover, a mechanism is required to control the choice of the other solution. The frameworks we propose maintain a list of potential solutions for use in crossover. We investigate the use of such lists at two conceptual levels. First, crossover is controlled at the hyper-heuristic level where no problem-specific information is required. Second, it is controlled at the problem domain level where problem-specific information is used to produce good-quality solutions to use in crossover. A number of selection hyper-heuristics are compared using these frameworks over three benchmark libraries with varying properties for an NP-hard optimisation problem: the multidimensional 0-1 knapsack problem. It is shown that allowing crossover to be managed at the domain level outperforms managing crossover at the hyper-heuristic level in this problem domain.

  14. Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial

    Directory of Open Access Journals (Sweden)

    Lanza FL

    2018-04-01

    Full Text Available Frank L Lanza,1 Agron Collaku,2 Dongzhou J Liu3 1Department of Gastroenterology, Houston Institute for Clinical Research, Houston, TX, USA; 2Biostatistics Department, GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA; 3Global Clinical Development, GlaxoSmithKline, Collegeville, PA, USA Background: While gastrointestinal (GI effects of standard ibuprofen and N-acetyl-p-­aminophenol (APAP have been reported, upper GI injury following treatment with fast-dissolving (FD formulations of these analgesics has not been investigated. We evaluated upper GI effects of over-the-counter doses of 2 FD ibuprofen products and 1 FD-APAP product. Methods: In a randomized, placebo-controlled, endoscopist-blinded, 4-way crossover study, 28 healthy subjects received FD ibuprofen 2×200 mg liquid capsules 3 times daily (TID, ibuprofen 2×200 mg tablets TID, FD-APAP 2×500 mg tablets 4 times daily (QID, and placebo 2×500 mg tablets QID for 7 days. The primary end point was gastric mucosal damage assessed by endoscopy using the Lanza scale: 0=normal stomach or proximal duodenum, 1=mucosal hemorrhages only, 2=1 or 2 erosions, 3=numerous (3–10 erosions, and 4=large number of erosions (>10 or ulcer. Secondary end points included duodenal mucosal damage (Lanza scale; gastroduodenal mucosal injury, classified as present (gastric and/or duodenal endoscopy score ≥2 or absent (gastric and/or duodenal endoscopy score <2; and number of hemorrhages, erosions, and ulcers counted separately in the stomach and duodenum. Results: Significantly greater gastric mucosal injury was observed after treatment with both ibuprofen products vs FD-APAP (p<0.0001 and p=0.0095, respectively. FD-APAP showed no difference from placebo (p=0.4794. The odds of having an incidence of gastroduodenal mucosal injury were over 6 times greater from FD ibuprofen liquid capsule treatment (odds ratio [OR]=6.19, 95% confidence interval [CI]: 1.60, 23.97 and over 3 times greater from ibuprofen

  15. Lycopene in the management of oral lichen planus: A placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Nisheeth Saawarn

    2011-01-01

    Settings and Design: This prospective, randomized, double-blind, placebo-controlled study was done in the Oral Medicine Department of a postgraduate teaching dental hospital in India. Materials and Methods: Thirty symptomatic OLP patients, randomly divided into two groups of 15 each, were administered lycopene 8 mg/day and an identical placebo, respectively, for 8 consecutive weeks. Burning sensation using visual analogue scale and overall treatment response using Tel Aviv-San Francisco scale were recorded at every visit. The data obtained were analyzed statistically using Wilcoxon Rank test, Mann-Whitney and Fischer′s Exact test. Results: A higher (84% reduction in burning sensation was seen in lycopene than in the placebo group (67%. All 15 (100% patients in the lycopene group showed 50% or more benefit and 11 (73.3% patients showed 70-100% benefit, while this number was only 10 and 4 (26.7%, respectively, in the placebo group. Conclusion: Lycopene was very effective in the management of OLP, and oxidative stress may have a role in disease pathogenesis.

  16. Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus.

    Science.gov (United States)

    Schilling, J; Mueller, R S

    2012-07-28

    Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.

  17. Efficacy of the Power Balance Silicone Wristband: a single-blind, randomized, triple placebo-controlled study.

    Science.gov (United States)

    Pothier, David D; Thiel, Gundula; Khoo, S G; Dillon, Wanda A; Sulway, Shaleen; Rutka, John A

    2012-06-01

    The Power Balance Silicone Wristband (Power Balance LLC, Laguna Niguel, CA) (power balance band; PBB) consists of a silicone wristband, incorporating two holograms, which is meant to confer improvements in balance on the wearer. Despite its popularity, the PBB has become somewhat controversial, with a number of articles being published in the news media regarding its efficacy. The PBB has not been formally evaluated but remains popular, largely based on anecdotal evidence. This study subjectively and objectively measured the effects of the PBB on balance in normal participants. A prospective, single-blind, randomized, triple placebo-controlled crossover study was undertaken. Twenty participants underwent measurement using the modified Test of Sensory Interaction on Balance (mCTSIB) and gave subjective feedback (visual analogue scale [VAS]) for each of four band conditions: no band, a silicone band, a deactivated PBB, and the PBB. Participants acted as their own controls. The mean of the four mCTSIB conditions (eyes open and closed on both firm and compliant surfaces) was calculated. This mean value and condition 4 of the mCTSIB were compared between band conditions using path length (PL) and root mean square (RMS) as outcome measures. No significant differences were found between band conditions for PL (p  =  .91 and p  =  .94, respectively) and RMS (p  =  .85 and p  =  .96, respectively). VASs also showed no difference between bands (p  =  .25). The PBB appears to have no effect on mCTSIB or VAS measurements of balance.

  18. A randomized, double-blind, placebo-controlled, crossover trial of mifepristone in Gulf War veterans with chronic multisymptom illness.

    Science.gov (United States)

    Golier, Julia A; Caramanica, Kimberly; Michaelides, Andreas C; Makotkine, Iouri; Schmeidler, James; Harvey, Philip D; Yehuda, Rachel

    2016-02-01

    No pharmacological treatments have been demonstrated to effectively treat chronic multisymptom illness (CMI) in Gulf War veterans (GWV). This study assessed the effect of the glucocorticoid receptor antagonist mifepristone in GWV with CMI. A randomized, double-blind, cross-over trial of mifepristone, with two six-week treatment phases separated by a one-month washout period, was conducted at a Veterans Affairs (VA) hospital between 2008 and 2011. Participants were randomized to receive either 200mg of mifepristone per day or matched placebo first. The primary clinical outcome measure was change in self-reported physical health. Neurocognitive functioning and self-reported measures of depression, PTSD, and fatigue were secondary outcomes. Sixty-five participants enrolled, of whom 36 were randomized and 32 (mean age, 49.1 (7.2) years) completed the study. Physical and mental health status and neurocognitive functioning were poor at baseline. Mifepristone treatment was not associated with improvement in self-reported physical health (p=0.838) or in other self-reported measures of mental health. Mifepristone treatment was significantly associated with improvements in verbal learning (p=0.008, d=0.508), in the absence of improvement in other cognitive measures (working memory (p=0.914), visual learning (p=0.643) and a global composite measure (p=0.937). Baseline morning cortisol levels and lysozyme IC50-DEX, a measure of peripheral glucocorticoid sensitivity, displayed a significant relationship with endpoint verbal learning scores (p=0.012 and p=0.007, respectively). The magnitude of cortisol change during treatment mediated the improvement in verbal learning. This study was negative for the primary and secondary clinical outcomes. However, the data suggest a moderate dose of mifepristone may have circumscribed cognitive-enhancing effects in CMI. Further study is warranted to determine whether and through which mechanisms mifepristone treatment can yield clinically

  19. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study.

    Science.gov (United States)

    Krymchantowski, A V; Barbosa, J S; Cheim, C; Alves, L A

    2001-03-01

    Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.

  20. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease.

    Science.gov (United States)

    Gaillard, S; Dupuis-Girod, S; Boutitie, F; Rivière, S; Morinière, S; Hatron, P-Y; Manfredi, G; Kaminsky, P; Capitaine, A-L; Roy, P; Gueyffier, F; Plauchu, H

    2014-09-01

    Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder associated with abnormal angiogenesis and disabling epistaxis. Tranexamic acid (TA) has been widely used in the treatment of these severe bleeds but with no properly designed trial. To demonstrate the efficacy of TA in epistaxis in HHT patients and to explore its safety of use. A randomized, placebo-controlled, double-blind, cross-over trial was conducted. Participants were randomized to receive TA (3 g a day) then placebo or the opposite sequence. The main analysis compared intra-individual mean duration of epistaxis under TA vs. placebo on a log scale. The primary outcome was the mean duration of epistaxis per month, assessed with specific grids to be completed by participants. The number of epistaxis episodes was recorded as a secondary outcome. A total of 118 randomized patients contributed to the statistical analysis. The mean duration of epistaxis per month was significantly shorter with TA than placebo (0.19 on the log scale; SD = 0.07; P = 0.005), corresponding to a decrease of 17.3% (15.7 min) in the duration of epistaxis per month (CI 95%, 5.5-27.6). The median number of epistaxis episodes per month was 22.1 episodes in the placebo arm vs. 23.3 episodes in the TA arm. No thrombophlebitis was observed. In the ATERO study, we demonstrated a significant decrease in the duration of epistaxis in HHT patients taking TA. No safety issues were recorded in our cohort of patients. © 2014 International Society on Thrombosis and Haemostasis.

  1. An algorithm for evaluating the ethics of a placebo-controlled trial.

    Science.gov (United States)

    Amdur, R J; Biddle, C J

    2001-10-20

    The purpose of this article is to clarify the decision points that are important to consider when evaluating the ethics of a placebo-controlled trial. The ethical requirements for research involving human subjects are reviewed, and the rationale for and potential problems with concomitant placebo control are explained. A series of case discussions are used to illustrate each decision point. The critical decision points in the evaluation of the ethics of a placebo-controlled trial are as follows: (i) Is placebo being used in place of standard therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity of standard therapy such that patients routinely refuse this treatment? (iv) Could the use of placebo result in severe suffering or irreversible harm? (v) Is the variability in the placebo response such that it is reasonable to consider other options for the control group? (vi) Would a reasonable person with an average degree of altruism and risk aversiveness agree to participate in this study? The algorithm presented in this article gives researchers and research monitors (such as Institutional Review Board members) the tools they need to evaluate the ethics of a study that uses concomitant placebo control. Copyright 2001 Wiley-Liss, Inc.

  2. Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in human experimental pain: a randomized placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Pascal H Vuilleumier

    Full Text Available Compounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam were studied using multiple experimental pain tests. Positive results would support further investigation of GABA agonism for the control of clinical pain.In a randomized double-blind crossover design, 16 healthy male volunteers received clobazam 20 mg, clonazepam 1 mg and tolterodine 1 mg (active placebo. The area of static hyperalgesia after intradermal capsaicin injection was the primary endpoint. Secondary endpoints were: area of dynamic hyperalgesia, response to von Frey hair stimulation, pressure pain thresholds, conditioned pain modulation, cutaneous and intramuscular electrical pain thresholds (1, 5 and 20 repeated stimulation, and pain during cuff algometry.For the primary endpoint, an increase in the area of static hyperalgesia was observed after administration of placebo (p<0.001, but not after clobazam and clonazepam. Results suggestive for an anti-hyperalgesic effect of the benzodiazepines were obtained with all three intramuscular pain models and with cuff algometry. No effect could be detected with the other pain models employed.Collectively, the results are suggestive for a possible anti-hyperalgesic effect of drugs acting at the GABAA-receptors in humans, particularly in models of secondary hyperalgesia and deep pain. The findings are not conclusive, but support further clinical research on pain modulation by GABAergic drugs. Because of the partial results, future research should focus on compounds acting selectively on subunits of the GABA complex, which may allow the achievement of higher receptor occupancy than unselective drugs. Our data also provide information on the most suitable experimental

  3. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder.

    Science.gov (United States)

    Westenberg, Herman G M; Stein, Dan J; Yang, Haichen; Li, David; Barbato, Luigi M

    2004-02-01

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.

  4. Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

    Science.gov (United States)

    Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

    2018-01-01

    Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Should we reconsider the routine use of placebo controls in clinical research?

    Directory of Open Access Journals (Sweden)

    Avins Andrew L

    2012-04-01

    Full Text Available Abstract Background Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. Methods We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. Results We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Conclusions Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

  6. Should we reconsider the routine use of placebo controls in clinical research?

    Science.gov (United States)

    Avins, Andrew L; Cherkin, Daniel C; Sherman, Karen J; Goldberg, Harley; Pressman, Alice

    2012-04-27

    Modern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice. We examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups. We find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition. Intentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

  7. Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder.

    Science.gov (United States)

    Soler, Joaquim; Pascual, Juan Carlos; Campins, Josefa; Barrachina, Judith; Puigdemont, Dolors; Alvarez, Enrique; Pérez, Victor

    2005-06-01

    The aim of this study was to determine the efficacy and safety of dialectical behavior therapy plus olanzapine compared with dialectical behavior therapy plus placebo in patients with borderline personality disorder. Sixty patients with borderline personality disorder were included in a 12-week, double-blind, placebo-controlled study. All patients received dialectical behavior therapy and were randomly assigned to receive either olanzapine or placebo following a 1-month baseline period. Seventy percent of the patients completed the 4-month trial. Combined treatment showed an overall improvement in most symptoms studied in both groups. Olanzapine was associated with a statistically significant improvement over placebo in depression, anxiety, and impulsivity/aggressive behavior. The mean dose of olanzapine was 8.83 mg/day. A combined psychotherapeutic plus pharmacological approach appears to lower dropout rates and constitutes an effective treatment for borderline personality disorder.

  8. Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study

    NARCIS (Netherlands)

    Nosten, F.; ter Kuile, F.; Maelankiri, L.; Chongsuphajaisiddhi, T.; Nopdonrattakoon, L.; Tangkitchot, S.; Boudreau, E.; Bunnag, D.; White, N. J.

    1994-01-01

    A double-blind, placebo-controlled study of mefloquine antimalarial prophylaxis in pregnancy (> 20 weeks of gestation) was conducted in 339 Karen women living in an area of multidrug-resistant malaria transmission on the Thai-Burmese border. Mefloquine gave > or = 86% (95% confidence interval [CI],

  9. Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Homa Sadeghian

    2015-01-01

    Full Text Available Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive and preventive (prophylactic treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants, and anti-epileptic drugs (valproate, gabapentin, etc. Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27, valproate 500 mg/d (n = 32 or placebo (n = 26. The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0% patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6% for valproate group and 4 (15.4% for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate.

  10. Immunomodulatory effects of ResistAid™: A randomized, double-blind, placebo-controlled, multidose study.

    Science.gov (United States)

    Udani, Jay K

    2013-01-01

    To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18-61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine).

  11. The effect of Lactobacillus brevis KB290 against irritable bowel syndrome: a placebo-controlled double-blind crossover trial

    Directory of Open Access Journals (Sweden)

    Murakami Katsumi

    2012-08-01

    Full Text Available Abstract Background Irritable bowel syndrome (IBS is a functional disorder of the digestive tract that causes chronic abdominal symptoms. We evaluated the effects of Lactobacillus brevis KB290 (KB290, which has been demonstrated to be effective at improving bowel movements and the composition of intestinal microflora, on IBS symptoms. Methods We performed a placebo control double-blind cross matched trial. Thirty-five males and females (aged 6 years and above who had been diagnosed with IBS according to the Rome III criteria were divided into 2 groups, and after a 4-week pre-trial observation period, they were administered test capsules containing KB290 or placebo for 4 weeks (consumption period I. Then, the capsule administration was suspended for 4 weeks in both groups (washout period, before the opposite capsules were administered for a further 4 weeks (consumption period II. Fecal samples were collected on the first day of the pre-consumption observation period, the last day of consumption period I, the last day of the washout period, and the last day of consumption period II. In addition, the subjects’ IBS symptoms and quality of life (QOL and any adverse events that they experienced were evaluated. Results No significant difference in IBS symptoms was noted among the various periods. However, the mean QOL scores were improved during the test capsule consumption. The frequencies of watery and mushy feces were significantly lower in the test capsule consumption period than during the pre-consumption observation period, and the frequency of abdominal pain was significantly reduced in the test capsule consumption period compared with the other periods. The frequency of the genus Bifidobacterium was significantly higher, and that of the genus Clostridium was significantly lower, after the test capsule consumption than after the placebo consumption. The frequencies of the genera Lactobacillus, Bacteroides, and Enterococcus were also

  12. A randomized, double-blind, crossover, placebo-controlled clinical trial to assess effects of the single ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase on oral malodor.

    Science.gov (United States)

    Nakano, Manabu; Shimizu, Eiju; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki

    2016-03-22

    The main components of oral malodor have been identified as volatile sulfur compounds (VSCs) including hydrogen sulfide (H2S) and methyl mercaptan (CH3SH). VSCs also play an important role in the progression of periodontal disease. The aim of the present study was to assess the effects of the single ingestion of a tablet containing 20 mg of lactoferrin, 2.6 mg of lactoperoxidase, and 2.6 mg of glucose oxidase on VSCs in the mouth. Subjects with VSCs greater than the olfactory threshold in their mouth air ingested a test or placebo tablet in two crossover phases. The concentrations of VSCs were monitored at baseline and 10 and 30 min after ingestion of the tablets using portable gas chromatography. Thirty-nine subjects were included in the efficacy analysis based on a full analysis set (FAS). The concentrations of total VSCs and H2S at 10 min were significantly lower in the test group than in the placebo group (-0.246 log ng/10 ml [95 % CI -0.395 to -0.098], P = 0.002; -0.349 log ng/10 ml; 95 % CI -0.506 to -0.192; P oxidase has suppressive effects on oral malodor. This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (number: UMIN000015140 , date of registration: 16/09/2014).

  13. Persistent User Bias in Case-Crossover Studies in Pharmacoepidemiology

    DEFF Research Database (Denmark)

    Hallas, Jesper; Pottegård, Anton; Wang, Shirley

    2016-01-01

    Studying the effect of chronic medication exposure by means of a case-crossover design may result in an upward-biased odds ratio. In this study, our aim was to assess the occurrence of this bias and to evaluate whether it is remedied by including a control group (the case-time-control design...... for the retinal detachment controls were similar, leading to near-null case-time-control estimates for all 3 medication classes. For wrist fracture and stroke, the odds ratios were higher for cases than for controls, and case-time-control odds ratios were consistently above unity, thus implying significant...... residual bias. In case-crossover studies of medications, contamination by persistent users confers a moderate bias upward, which is partly remedied by using a control group. The optimal strategy for dealing with this problem is currently unknown....

  14. Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia.

    Science.gov (United States)

    Schabus, Manuel; Griessenberger, Hermann; Gnjezda, Maria-Teresa; Heib, Dominik P J; Wislowska, Malgorzata; Hoedlmoser, Kerstin

    2017-04-01

    See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article.Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the 'law of effect'. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 12-15 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral electroencephalographic

  15. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sara Llufriu

    Full Text Available Uncontrolled studies of mesenchymal stem cells (MSCs in multiple sclerosis suggested some beneficial effect. In this randomized, double-blind, placebo-controlled, crossover phase II study we investigated their safety and efficacy in relapsing-remitting multiple sclerosis patients. Efficacy was evaluated in terms of cumulative number of gadolinium-enhancing lesions (GEL on magnetic resonance imaging (MRI at 6 months and at the end of the study.Patients unresponsive to conventional therapy, defined by at least 1 relapse and/or GEL on MRI scan in past 12 months, disease duration 2 to 10 years and Expanded Disability Status Scale (EDSS 3.0-6.5 were randomized to receive IV 1-2×10(6 bone-marrow-derived-MSCs/Kg or placebo. After 6 months, the treatment was reversed and patients were followed-up for another 6 months. Secondary endpoints were clinical outcomes (relapses and disability by EDSS and MS Functional Composite, and several brain MRI and optical coherence tomography measures. Immunological tests were explored to assess the immunomodulatory effects.At baseline 9 patients were randomized to receive MSCs (n = 5 or placebo (n = 4. One patient on placebo withdrew after having 3 relapses in the first 5 months. We did not identify any serious adverse events. At 6 months, patients treated with MSCs had a trend to lower mean cumulative number of GEL (3.1, 95% CI = 1.1-8.8 vs 12.3, 95% CI = 4.4-34.5, p = 0.064, and at the end of study to reduced mean GEL (-2.8±5.9 vs 3±5.4, p = 0.075. No significant treatment differences were detected in the secondary endpoints. We observed a non-significant decrease of the frequency of Th1 (CD4+ IFN-γ+ cells in blood of MSCs treated patients.Bone-marrow-MSCs are safe and may reduce inflammatory MRI parameters supporting their immunomodulatory properties. ClinicalTrials.gov NCT01228266.

  16. Auricular Acupuncture for Exam Anxiety in Medical Students-A Randomized Crossover Investigation.

    Directory of Open Access Journals (Sweden)

    Catharina Klausenitz

    Full Text Available Auricular acupuncture (AA is effective in the treatment of preoperative anxiety. The aim was to investigate whether AA can reduce exam anxiety as compared to placebo and no intervention. Forty-four medical students were randomized to receive AA, placebo, or no intervention in a crossover manner and subsequently completed three comparable oral anatomy exams with an interval of 1 month between the exams/interventions. AA was applied using indwelling fixed needles bilaterally at points MA-IC1, MA-TF1, MA-SC, MA-AT1 and MA-TG one day prior to each exam. Placebo needles were used as control. Levels of anxiety were measured using a visual analogue scale before and after each intervention as well as before each exam. Additional measures included the State-Trait-Anxiety Inventory, duration of sleep at night, blood pressure, heart rate and the extent of participant blinding. All included participants finished the study. Anxiety levels were reduced after AA and placebo intervention compared to baseline and the no intervention condition (p < 0.003. AA was better at reducing anxiety than placebo in the evening before the exam (p = 0.018. Participants were able to distinguish between AA and placebo intervention. Both AA and placebo interventions reduced exam anxiety in medical students. The superiority of AA over placebo may be due to insufficient blinding of participants.

  17. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

    NARCIS (Netherlands)

    Westenberg, HGM; Stein, DJ; Yang, HC; Li, D; Barbato, LM

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to

  18. Melatonin for chronic sleep onset insomnia in children: A Randomized placebo-controlled study

    NARCIS (Netherlands)

    Smits, M.G.; Nagtegaal, J.E.; Heijden, J.A.M. van der; Coenen, A.M.L.; Kerkhof, G.A.

    2001-01-01

    To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to

  19. Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Motokazu Kato

    Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

  20. Lack of effect of intravenous immunoglobulins on tics : A double-blind placebo-controlled study

    NARCIS (Netherlands)

    Hoekstra, PJ; Minderaa, RB; Kallenberg, CGM

    Background: Case studies and a placebo-controlled study previously suggested the effectiveness of immunomodulatory therapy in patients with tic or related disorders whose symptoms show a relationship with streptococcal infections. No data are available on the effectiveness of intravenous

  1. Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study.

    Science.gov (United States)

    Guarda-Nardini, Luca; Manfredini, Daniele; Salamone, Milena; Salmaso, Luigi; Tonello, Stefano; Ferronato, Giuseppe

    2008-04-01

    The present investigation is a preliminary double-blind, controlled placebo, randomized clinical trial with a six month follow-up period. The study aimed to assess the efficacy of type A botulinum toxin (Botox, Allergan, Inc. Irvine, CA) to treat myofascial pain symptoms and to reduce muscle hyperactivity in bruxers. Twenty patients (ten males, ten females; age range 25-45) with a clinical diagnosis of bruxism and myofascial pain of the masticatory muscles were enrolled in a double-blind, controlled placebo, randomized clinical trial, with a treatment group (ten subjects treated with botulinum toxin injections- BTX-A) and a control group (ten subjects treated with saline placebo injections). A number of objective and subjective clinical parameters (pain at rest and during chewing; mastication efficiency; maximum nonassisted and assisted mouth opening, protrusive and laterotrusive movements; functional limitation during usual jaw movements; subjective efficacy of the treatment; tolerance of the treatment) were assessed at baseline time and at one week, one month, and six months follow-up appointments. Descriptive analysis showed that improvements in both objective (range of mandibular movements) and subjective (pain at rest; pain during chewing) clinical outcome variables were higher in the Botox treated group than in the placebo treated subjects. Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects. Differences were not significant in some cases due to the small sample size. Results from the present study supported the efficacy of BTX-A to reduce myofascial pain symptoms in bruxers, and provided pilot data which need to be confirmed by further research using larger samples.

  2. Clinical effects of buspirone in social phobia : A double-blind placebo-controlled study

    NARCIS (Netherlands)

    denBoer, JA; Westenberg, HGM; Pian, KLH

    Background: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. Method: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled

  3. Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study.

    Science.gov (United States)

    Windischberger, Christian; Lanzenberger, Rupert; Holik, Alexander; Spindelegger, Christoph; Stein, Patrycja; Moser, Ulrike; Gerstl, Florian; Fink, Martin; Moser, Ewald; Kasper, Siegfried

    2010-01-15

    Area-specific and stimulation-dependent changes of human brain activation by selective serotonin reuptake inhibitors (SSRI) are an important issue for improved understanding of treatment mechanisms, given the frequent prescription of these drugs in depression and anxiety disorders. The aim of this neuroimaging study was to investigate differences in BOLD-signal caused by administration of the SSRIs escitalopram and citalopram using pharmacological functional magnetic resonance imaging (pharmaco-fMRI). Eighteen healthy subjects participated in a placebo-controlled, randomized, double-blind study in cross-over repeated measures design. Each volunteer performed facial emotional discrimination and a sensorimotor control paradigm during three scanning sessions. Citalopram (20 mg/d), escitalopram (10 mg/d) and placebo were administered for 10 days each with a drug-free period of at least 21 days. Significant pharmacological effects on BOLD-signal were found in the amygdala, medial frontal gyrus, parahippocampal, fusiform and middle temporal gyri. Post-hoc t-tests revealed decreased BOLD-signal in the right amygdala and left parahippocampal gyrus in both pharmacological conditions, compared to placebo. Escitalopram, compared to citalopram, induced a decrease of BOLD-signal in the medial frontal gyrus and an increase in the right fusiform and left parahippocampal gyri. Drug effects were concentrated in brain regions with dense serotonergic projections. Both escitalopram and citalopram attenuated BOLD-signal in the amygdala and parahippocampal cortex to emotionally significant stimuli compared to control stimuli. We believe that reduced reactivity in the medial frontal gyrus found for escitalopram compared to citalopram administration might explain the response differences between study drugs as demonstrated in previous clinical trials.

  4. The efficacy of agomelatine in elderly patients with recurrent major depressive disorder: a placebo-controlled study.

    Science.gov (United States)

    Heun, Reinhard; Ahokas, Antti; Boyer, Patrice; Giménez-Montesinos, Natalia; Pontes-Soares, Fernando; Olivier, Valérie

    2013-06-01

    The present placebo-controlled study evaluated the efficacy, tolerability, and safety of 8-week treatment with agomelatine (25-50 mg/d by mouth) in elderly patients with major depressive disorder (MDD). Elderly outpatients aged ≥ 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD (DSM-IV-TR) were recruited in 27 clinical centers in Argentina, Finland, Mexico, Portugal, and Romania from November 2009 to October 2011. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17) total score. A total of 222 elderly patients entered the study (151 in the agomelatine group, 71 in the placebo group), including 69 patients aged 75 years and older. Agomelatine improved depressive symptoms in the elderly population, as evaluated by the HDRS17 total score, in terms of last postbaseline value (agomelatine-placebo difference: mean estimate [standard error] = 2.67 [1.06] points; P = .013) and response to treatment (agomelatine, 59.5%; placebo, 38.6%; P = .004). The agomelatine-placebo difference according to the Clinical Global Impressions-Severity of Illness scale (CGI-S) score was 0.48 (0.19). The agomelatine-placebo difference (estimate [standard error]) for remission on the HDRS17 was 6.9% (4.7%) and did not achieve statistical significance (P = .179, post hoc analysis). Clinically relevant effects of agomelatine were confirmed on all end points in the subset of severely depressed patients (HDRS17 total score ≥ 25 and CGI-S score ≥ 5 at baseline). Agomelatine was well tolerated by patients, with only minimal distinctions from placebo. The present study provides the first evidence that an 8-week treatment with agomelatine 25-50 mg/d efficiently relieves depressive symptoms and is well tolerated in elderly depressed patients older than 65 years. Controlled-Trials.com identifier: ISRCTN57507360. © Copyright 2011 Physicians Postgraduate Press, Inc.

  5. Mast cell stabilizers as a potential treatment for Irritable bowel syndrome: A randomized placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    N Ebrahimi Daryani

    2009-08-01

    Full Text Available Objectives: Mast cells are believed to play a role in irritable bowel syndrome pathogenesis and symptom genesis due to their close neighborhood to gastrointestinal innervations. This study was designed to evaluate the efficacy of orally administered cromolyn for reduction of symptoms in patients with irritable bowel syndrome (IBS. Material and Methods s: A randomized placebo-controlled double-blinded 6×6 weeks cross-over study was performed in a private gastrointestinal clinic. 10 patients were allocated to group A and 6 patients to group B. Patients in group A received 150 mg cromolyn divided in three equal doses for the first 6 weeks and placebo for the next 6 weeks but patients in group B received placebo for the first 6 weeks and cromolyn in the next 6 weeks. Weekly evaluation was performed and visual analogue scale was used to determine severity of symptoms. Results: Sixteen patients completed the study. Mean age of the patients was 40.3 ± 10.9 years old [range: 24-57]. Eight patients had D-IBS (Diarrhea dominant and other 8 had C-IBS (Constipation dominant. Both cromolyn sodium and the placebo decreased the severity of bloating (Freidman test, p 0.001 and 0.006 respectively. The severity of the main symptom (diarrhea or constipation did not decrease in patients of group A and B who were treated with different sequences of the drug or placebo. The severity of pain decreased drastically after 6th week of treatment with cromolyn. Freidman test showed a significant difference between the pain levels of the former defined treatment spots (p 0.01, and 0.02 for patients in group A and B, respectively. No adverse drug reactions were observed during the study. Conclusion: In conclusion, long term administration of cromolyn seems to be partially effective for treatment of abdominal pain in patients with IBS while main symptoms (diarrhea or constipation might not decrease during this treatment.

  6. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    International Nuclear Information System (INIS)

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-01-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis

  7. Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

    Directory of Open Access Journals (Sweden)

    Norio Sugawara

    Full Text Available Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs.The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan.Using a cross-sectional design, we recruited patients (n = 251 aged 47.7±13.2 (mean±SD with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials.The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation.Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

  8. Choto-san in the treatment of vascular dementia: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Terasawa, K; Shimada, Y; Kita, T; Yamamoto, T; Tosa, H; Tanaka, N; Saito, Y; Kanaki, E; Goto, S; Mizushima, N; Fujioka, M; Takase, S; Seki, H; Kimura, I; Ogawa, T; Nakamura, S; Araki, G; Maruyama, I; Maruyama, Y; Takaori, S

    1997-03-01

    In an earlier placebo-controlled study, we demonstrated that a kampo (Japanese herbal) medicine called Choto-san (Diao-Teng-San in Chinese) was effective in treating vascular dementia. To evaluate its efficacy using more objective criteria, we carried out a multi-center, double-blind study of Choto-san extract (7.5 g/day) and a placebo, each given three times a day for 12 weeks to patients suffering from this condition. The study enrolled and analyzed 139 patients, 50 males and 89 females, with a mean age of 76.6 years. Choto-san was statistically superior to the placebo in global improvement rating, utility rating, global improvement rating of subjective symptoms, global improvement rating of psychiatric symptoms and global improvement rating of disturbance in daily living activities. Such items as spontaneity of conversation, lack of facial expression, decline in simple mathematical ability, global intellectual ability, nocturnal delirium, sleep disturbance, hallucination or delusion, and putting on and taking off clothes were significantly improved at one or more evaluation points in those taking Choto-san compared to those taking the placebo. Furthermore, the change in revised version of Hasegawa's dementia scale from the beginning point in Choto-san group was tended to be higher than that in placebo group with no statistical significance. These results suggest that Choto-san is effective in the treatment of vascular dementia. Copyright © 1997 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.

  9. An alternative approach to treating lateral epicondylitis. A randomized, placebo-controlled, double-blinded study

    NARCIS (Netherlands)

    Nourbakhsh, Mohammad Reza; Fearon, Frank J.

    Objective: To investigate the effect of noxious level electrical stimulation on pain, grip strength and functional abilities in subjects with chronic lateral epicondylitis. Design: Randomized, placebo-control, double-blinded study. Setting: Physical Therapy Department, North Georgia College and

  10. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Kupchak Brian R

    2009-07-01

    Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

  11. Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects

    Directory of Open Access Journals (Sweden)

    Vinson JA

    2012-01-01

    Full Text Available Joe A Vinson1, Bryan R Burnham3, Mysore V Nagendran31Chemistry Department, 2Psychology Department, University of Scranton, Scranton, PA, USA; 3Health Sciences Clinic, Bangalore, IndiaBackground: Adult weight gain and obesity have become worldwide problems. Issues of cost and potential side effects of prescription weight loss drugs have led overweight and obese adults to try nutraceuticals that may aid weight loss. One promising nutraceutical is green coffee extract, which contains high concentrations of chlorogenic acids hat are known to have health benefits and to influence glucose and fat metabolism. A 22-week crossover study was conducted to examine the efficacy and safety of a commercial green coffee extract product GCA™ at reducing weight and body mass in 16 overweight adults.Methods: Subjects received high-dose GCA (1050 mg, low-dose GCA (700 mg, or placebo in separate six-week treatment periods followed by two-week washout periods to reduce any influence of preceding treatment. Treatments were counterbalanced between subjects. Primary measurements were body weight, body mass index, and percent body fat. Heart rate and blood pressure were also measured.Results: Significant reductions were observed in body weight (-8.04 ± 2.31 kg, body mass index (-2.92 ± 0.85 kg/m2, and percent body fat (-4.44% ± 2.00%, as well as a small decrease in heart rate (-2.56 ± 2.85 beats per minute, but with no significant changes to diet over the course of the study. Importantly, the decreases occurred when subjects were taking GCA. Body mass index for six subjects shifted from preobesity to the normal weight range (<25.00 kg/m2.Conclusion: The results are consistent with human and animal studies and a meta-analysis of the efficacy of green coffee extract in weight loss. The results suggest that GCA may be an effective nutraceutical in reducing weight in preobese adults, and may be an inexpensive means of preventing obesity in overweight adults

  12. Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development.

    Science.gov (United States)

    Corbett, Blythe A; Bales, Karen L; Swain, Deanna; Sanders, Kevin; Weinstein, Tamara A R; Muglia, Louis J

    2016-01-01

    Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor "Condition" (hydrocortisone/placebo) and "Time" (pre and post) and the between-subject factor "Group" (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. There was a significant Time × Condition × Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While

  13. Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study

    Directory of Open Access Journals (Sweden)

    Andrea T. White

    2015-01-01

    Full Text Available Pregabalin, an approved treatment for fibromyalgia (FM, has been shown to decrease sympathetic nervous system (SNS activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported. Methods. Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP, heart rate (HR, and ratings of perceived exertion (RPE during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls. Results. On placebo, exercise RPE and BP were significantly higher in FM patients than controls (p0.26. Cardiovascular responses of nonresponders (n=7 were not altered by pregabalin. In responders, pregabalin improved ratings of fatigue and pain (p<0.04, but negative effects on pain and fatigue were seen in nonresponders. Conclusions. These preliminary findings suggest that pregabalin may normalize cardiovascular and subjective responses to exercise in many FM patients.

  14. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study

    OpenAIRE

    Krymchantowski,Abouch V.; Barbosa,Jackeline S.; Cheim,Celia; Alves,Luiz A.

    2001-01-01

    Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, wer...

  15. A double-blind, randomized, placebo-controlled trial studying the effects of Saccharomyces boulardii on the gastrointestinal tolerability, safety, and pharmacokinetics of miglustat.

    Science.gov (United States)

    Remenova, Tatiana; Morand, Olivier; Amato, Dominick; Chadha-Boreham, Harbajan; Tsurutani, Scott; Marquardt, Thorsten

    2015-06-19

    Gastrointestinal (GI) disturbances such as diarrhea and flatulence are the most frequent adverse effects associated with miglustat therapy in type 1 Gaucher disease (GD1) and Niemann-Pick disease type C (NP-C), and the most common recorded reason for stopping treatment during clinical trials and in clinical practice settings. Miglustat-related GI disturbances are thought to arise from the inhibition of intestinal disaccharidases, mainly sucrase isomaltase. We report the effects of a co-administered dietary probiotic, S. boulardii, on the GI tolerability of miglustat in healthy adult subjects. In a double-blind, placebo-controlled, two-period, two-treatment cross-over trial, healthy adult male and female subjects were randomly allocated to treatment sequences, A-B and B-A (treatment A - miglustat 100 mg t.i.d. + placebo; treatment B - miglustat 100 mg t.i.d. + S. boulardii [500 mg, b.i.d.]). GI tolerability data were collected in patient diaries. The primary endpoint was the total number of 'diarrhea days' (≥3 loose stools within a 24-h period meeting Bristol Stool Scores [BSS] 6-7) based on WHO criteria. Secondary endpoints comprised numerous other diarrhea and GI tolerability indices. Twenty-one subjects received randomized therapy in each treatment sequence (total N = 42), and overall, 37 (88 %) subjects completed the study. The total number of diarrhea days was boulardii (0.8 [2.4] days) than with miglustat + placebo (1.3 [2.4] days), but the paired treatment difference was not statistically significant (-0.5 [2.4] days; p = 0.159). However, a significant treatment difference (-0.7 [1.9]; p boulardii (73 %). There were no between-treatment differences in miglustat pharmacokinetics. Although the primary endpoint was not met, the results of the post-hoc analysis suggest that co-administration of miglustat with S. boulardii might improve GI tolerability.

  16. Effect of three different dosages of magnesium sulfate on attenuating hemodynamic responses after electroconvulsive therapy: a randomized, double-blind, placebo-controlled trial

    International Nuclear Information System (INIS)

    Honarmand, A.; Safavi, M.; Mehdizadeh, F.; Salehi, M.

    2012-01-01

    Objective: The purpose of this randomized, double-blind, placebo-controlled crossover study was to compare the efficacy of three different dosages of MgSO/sub 4/ administration (10, 20, and 30 mg/kg) versus placebo on attenuation of cardiovascular response to electroconvulsive therapy (ECT). Methodology: Thirty-five adult patients scheduled for 8 ECT sessions were randomly assigned to be allocated twice into one of the four study groups: MgSO/sub 4/ 10 mg/kg (M10), MgSO/sub 4/ 20 mg/ kg (M20), MgSO/sub 4/ 30 mg/kg (M30), and placebo control (P). Systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) and heart rate (HR) were recorded at 0, 1, 3, and 10 minutes after termination of ECT-induced seizures. Duration of electroencephalographs (EEGs) and motor seizures and peak HR during convulsions were also recorded. Results: Changes in SAP, DAP, and MAP were significantly attenuated at 0, one, and three minutes after ECT in groups M20 and M30 compared with group P (P< 0.05). Peak HR changes were significantly less in groups M20 and M30 compared with groups M10 and P (P< 0.05). Duration of motor and EEG seizure activity was not significantly different among the four groups. Conclusion: Administration of either 20 or 30 mg/kg MgSO/sub 4/ significantly attenuated increased blood pressure and peak HR after ECT without decreasing seizure duration. (author)

  17. Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

    Science.gov (United States)

    Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

    1998-01-01

    OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition

  18. Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study.

    Science.gov (United States)

    D'Angelo, Simona; Fracassi, Federico; Bresciani, Francesca; Galuppi, Roberta; Diana, Alessia; Linta, Nikolina; Bettini, Giuliano; Morini, Maria; Pietra, Marco

    2018-03-03

    Saccharomyces boulardii is used to treat acute and chronic enteropathies in humans, but to date, no studies have evaluated the use of this yeast in dogs. The current study, a prospective non-randomised, double-blinded, placebo-controlled study, evaluated the effects of S boulardii in healthy dogs and dogs with chronic enteropathies (CE). Four healthy dogs and 20 dogs with CE were included. In healthy dogs, S boulardii was administered for 10 days. Possible short-term adverse effects were recorded, and quantitative stool cultures for yeasts were performed. In dogs with CE, S boulardii or a placebo was administered in addition to standard treatment protocols. Canine Chronic Enteropathy Clinical Activity Index, abdominal ultrasonography, gastroenteroscopy and histology were performed at the time of diagnosis and after 60 days of treatment. In healthy dogs, S boulardii reached a steady state in five days and was completely eliminated on day 4 after administration. No short-term side effects were seen. Clinical activity index, stool frequency, stool consistency and body condition score improved significantly in dogs with CE receiving S boulardii versus the placebo. In conclusion, S boulardii can be safely used in dogs with CE and seems to achieve better control of clinical signs than standard therapy alone. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial.

    Science.gov (United States)

    Kuppens, R J; Mahabier, E F; Bakker, N E; Siemensma, E P C; Donze, S H; Hokken-Koelega, A C S

    2016-11-16

    Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m 2 /day), both during 1 year. Total (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

  20. Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

    Science.gov (United States)

    Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

    2002-04-01

    To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

  1. The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate.

    Science.gov (United States)

    Drijgers, Rosa L; Verhey, Frans R J; Tissingh, Gerrit; van Domburg, Peter H M F; Aalten, Pauline; Leentjens, Albert F G

    2012-09-15

    In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence.

    LENUS (Irish Health Repository)

    Farren, Conor K

    2009-01-01

    Significant preclinical evidence exists for a synergistic interaction between the opioid and the serotonin systems in determining alcohol consumption. Naltrexone, an opiate receptor antagonist, is approved for the treatment of alcohol dependence. This double-blind placebo-controlled study examined whether the efficacy of naltrexone would be augmented by concurrent treatment with sertraline, a selective serotonin receptor uptake inhibitor (SSRI).

  3. The effect of montelukast on early-life wheezing: A randomized, double-blinded placebo-controlled study.

    Science.gov (United States)

    Keskin, Ozlem; Arik Yilmaz, Ebru; Motzkus, Christine; Sackesen, Cansin; Lilly, Craig M; Kalayci, Omer

    2018-02-01

    Cysteinyl-leukotrienes are increased in the airways of infants with virus-associated wheezing. We aimed to determine the effects of a cysteinyl-leukotriene-1 receptor antagonist on symptoms during an early-life wheezing illness and to investigate the factors that affect the response to this drug. This placebo-controlled double-blinded randomized controlled trial recruited children aged 3-36 months with wheezing illness and randomized to active drug or placebo for 56 days. A symptom score diary (SSD) was kept by the children's caregivers. One-hundred patients completed the study, and 62 (30 montelukast and 32 placebo) were analyzed. There were no significant differences in the percent of symptom-free days, symptom scores, and the need for rescue salbutamol between the two groups. However, the percent of symptom-free days within the first week was significantly higher for the montelukast than for the placebo group (13.8 ± 4.1% vs. 5.4 ± 3.4%; P = 0.028); wheezing score at 7th day was significantly lower for the montelukast than for the placebo group (0.5 ± 0.1 vs. 1.4 ± 0.2; P = 0.002). In addition, the number of inhaled ß 2 -agonist rescue episodes per day during the first week was significantly lower for the montelukast compared with the placebo group (12.7 ± 1.8 vs. 19.2 ± 1.6; P = 0.013). Conclusions Our results indicate that montelukast may be effective for reducing caregiver-observed wheezing and the need for salbutamol during the first week of treatment for early-life wheezing. The impact for caregivers and the optimal duration of treatment will need to be explored in studies of larger size. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  4. Effect of Blinding With a New Pragmatic Placebo Needle

    Science.gov (United States)

    Liu, Baoyan; Xu, Huanfang; Ma, Rui; Mo, Qian; Yan, Shiyan; Liu, Zhishun

    2014-01-01

    Abstract Placebo control is a useful method for determining the efficacy of a therapy. In acupuncture researches, the preferred method for placebo control is acupuncture using a placebo needle that has a blunt tip and achieves no skin penetration. We performed a crossover study to validate the blinding effect of a new type of placebo needle. Sixty volunteers were randomized to receive acupuncture using 2 types of needles with different sequences: sequence AB, involving first the pragmatic placebo needle and then the real needle, and sequence BA, in a reverse order. Placebo acupuncture was performed by administering the placebo needle through an adhesive pad without skin penetration on the acupoints LI4, RN12, BL25, and BL36. Real acupuncture was performed by needling through the pad and penetrating the skin to 15 mm using a real needle on the same acupoints. The acupuncture was administered every other day with 3 sessions for 1 type of needle. The primary outcome was the perception of needle penetration. Besides degree of acupuncture pain, type, and degree of needle sensation, needle acceptability and factors influencing the subject blinding effect were assessed. Needle penetration was felt by 100%, 90% (54/60), 88.3% (53/60), and 95% (57/60) of volunteers receiving placebo acupuncture and 98.3% (59/60), 96.7% (58/60), 95% (57/60), and 95% (57/60) of volunteers receiving real acupuncture on LI4, RN12, BL25, and BL36, respectively. Differences of the volunteers’ perception of needle penetration between the placebo needle and real needle were not significant for the 4 acupoints (all P > 0.05). Volunteers experienced fewer distension sensations (P = 0.01), a lower degree of needle sensation (P = 0.007), and less pain (P = 0.006) during placebo acupuncture than during real acupuncture. The placebo needle was more easily accepted than the real needle (OR = 1.63, 95% CI, 1.01–2.64). The influences of age, sex, educational level, acupuncture

  5. Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation, in the Treatment of Erectile Dysfunction: A Randomized Crossover Study.

    Science.gov (United States)

    Ralph, David J; Eardley, Ian; Taubel, Jorg; Terrill, Paul; Holland, Tim

    2018-02-01

    Current treatments for erectile dysfunction (ED) have some limitations. This study evaluated the efficacy and tolerability of MED2005, a 0.2% glyceryl trinitrate topical gel, formulated into an enhanced absorption topical delivery system (DermaSys), administered on demand, in the treatment of ED. This randomized, double-blinded, placebo-controlled, phase II crossover trial involved 232 men with ED (231 treated, 230 assessed for efficacy) and their partners. After a 4-week run-in period, patients were randomized to 1 of 2 treatment sequences, MED2005-placebo or placebo-MED2005. Each treatment was given for 4 weeks, separated by a 1-week washout interval. Efficacy was assessed by the International Index of Erectile Function (IIEF), the Sexual Encounter Profile, a Global Assessment Questionnaire (GAQ), and specific questions about the onset and offset of action and treatment preferences (patients and partners). The primary outcome measure was the IIEF erectile function domain (IIEF-EF) score. Other efficacy assessments were secondary outcomes. The mean baseline IIEF-EF score was 17.1 (SD = 5.7), and this increased to 19.6 (SD = 7.5) after MED2005 treatment and 18.5 (SD = 6.7) after placebo (P = .0132). Overall, 23.1% of patients showed a clinically relevant (≥4-point) increase in IIEF-EF scores after treatment with MED2005 only compared with 14.5% who responded after MED2005 and placebo, 14.0% who responded after placebo only, and 48.4% who did not respond after either treatment (P = .0272). MED2005 also was associated with significant improvements compared with placebo in the other IIEF domains, and this was consistent with patients' and partners' responses to the GAQ. For all assessments, significant effects of MED2005 were seen primarily in patients with mild ED. The start of erection was noticed within 5 and 10 minutes in 44.2% and 69.5%, respectively, of all intercourse attempts with MED2005. Patients and partners showed significant preferences for MED2005

  6. Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea.

    Science.gov (United States)

    Money, Mary E; Walkowiak, Jaroslaw; Virgilio, Chris; Talley, Nicholas J

    2011-01-01

    OBJECTIVE: To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). DESIGN: An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline 'trigger meals' and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. SETTING: Outpatient internal medicine practice clinic. PATIENTS: 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised 'food triggers', no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11-30 years and 16% for more than 40 years. INTERVENTIONS: After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. MAIN OUTCOME MEASURES: The primary analysis was number of patients who chose PEZ over placebo for the extended use. RESULTS: Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p≤0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. CONCLUSIONS: PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation.

  7. Effects of a Bovine Lactoferrin Formulation from Cow’s Milk on Menstrual Distress in Volunteers: A Randomized, Crossover Study

    Directory of Open Access Journals (Sweden)

    Hiroshi M. Ueno

    2016-05-01

    Full Text Available Dysmenorrhea is a highly prevalent complaint and highly undiagnosed gynecologic condition. Dairy products have a potential in the management of menstrual distress, and bovine lactoferrin can help the subjective dysphoria associated with dysmenorrhea. In the present study, we aimed to investigate the effects of a lactoferrin formulation isolated from cow’s milk on menstrual symptoms in volunteers. A double-blind, randomized, placebo-controlled, crossover study of the iron-lactoferrin complex (FeLf was performed in thirty-five healthy Japanese women. Participants received the 150 mg FeLf (per day or placebo from day ten of the luteal phase to day four of the follicular phase. The Moos Menstrual Distress Questionnaire (MDQ was measured for menstrual distress, and heart rate variability was measured as an index of autonomic nerve balance during menses. A visual analog scale for menstrual pain, and a verbal rating scale for quality of life during the first three days of menstruation were measured. The MDQ score for the automatic nervous system subscale was lower and the parasympathetic nervous system activity was greater in FeLf than in placebo for intention-to-treat or per-protocol populations. The other variables were not different between the groups. No treatment-related side effects were observed during the study. The results indicate that FeLf can provide a beneficial effect on the psychological symptoms in women affected by menstrual distress.

  8. Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

    Science.gov (United States)

    Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

    2014-10-01

    Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

  9. Effects of supplementation with n-3 polyunsaturated fatty acids on cognitive performance and cardiometabolic risk markers in healthy 51 to 72 years old subjects: a randomized controlled cross-over study

    Directory of Open Access Journals (Sweden)

    Nilsson Anne

    2012-11-01

    Full Text Available Abstract Background Higher plasma n-3 polyunsaturated fatty acids (PUFA have been associated with a lower risk of age related cognitive decline, and to beneficially affect cardiometabolic risk factors. A relation exists between metabolic disorders such as diabetes type 2 and cognitive decline. Results regarding the potential effects of n-3 PUFA on risk factors in healthy subjects are divergent, and studies regarding the possible relation between cardiometabolic parameters and cognitive performance are scarce. The objective was to evaluate the effects of five weeks intake of long chain n-3 PUFA on cognitive performance in healthy individuals, and to exploit the possible relation between outcomes in cognitive tests to cardiometabolic risk parameters. Methods Fish oil n-3 PUFA (3g daily were consumed during 5weeks separated by a 5 week washout period in a cross-over placebo controlled study, including 40 healthy middle aged to elderly subjects. Cognitive performance was determined by tests measuring working memory (WM and selective attention. Results Supplementation with n-3 PUFA resulted in better performance in the WM-test compared with placebo (p p p p = 0.05, and s-TNF-α (p = 0.05, were inversely related to the performance in cognitive tests. Conclusions Intake of n-3 PUFA improved cognitive performance in healthy subjects after five weeks compared with placebo. In addition, inverse relations were obtained between cardiometabolic risk factors and cognitive performance, indicating a potential of dietary prevention strategies to delay onset of metabolic disorders and associated cognitive decline.

  10. The Effect of Prior Caffeine Consumption on Neuropsychological Test Performance: A Placebo-Controlled Study.

    Science.gov (United States)

    Walters, Elizabeth R; Lesk, Valerie E

    2016-01-01

    The aim of this study was to investigate whether the prior consumption of 200 mg of pure caffeine affected neuropsychological test scores in a group of elderly participants aged over 60 years. Using a double-blind placebo versus caffeine design, participants were randomly assigned to receive 200 mg of caffeine or placebo. A neuropsychological assessment testing the domains of general cognitive function, processing speed, semantic memory, episodic memory, executive function, working memory and short-term memory was carried out. Significant interaction effects between age, caffeine and scores of executive function and processing speed were found; participants who had received caffeine showed a decline in performance with increasing age. This effect was not seen for participants who received placebo. The results highlight the need to consider and control prior caffeine consumption when scoring neuropsychological assessments in the elderly, which is important for accuracy of diagnosis and corresponding normative data. © 2016 S. Karger AG, Basel.

  11. Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Dalbeth, Nicola; Saag, Kenneth G; Palmer, William E; Choi, Hyon K; Hunt, Barbara; MacDonald, Patricia A; Thienel, Ulrich; Gunawardhana, Lhanoo

    2017-12-01

    To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares). In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment (change from baseline -0.43 versus -0.07; P gout flares (29.3% versus 41.4%; P gout flares in subjects with early gout. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

  12. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Antioxidative Activity of Onion Peel Extract in Obese Women: A Randomized, Double-blind, Placebo Controlled Study.

    Science.gov (United States)

    Kim, Kyung-Ah; Yim, Jung-Eun

    2015-09-01

    Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman. This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively. Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption. These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women.

  14. Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial

    Directory of Open Access Journals (Sweden)

    R. J. Kuppens

    2016-11-01

    Full Text Available Abstract Background Patients with Prader-Willi syndrome (PWS have a cognitive impairment. Growth hormone (GH treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Method Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m2/day, both during 1 year. Results Total (TIQ, verbal (VIQ and performance IQ (PIQ did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322. Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Conclusions Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. Trial registration ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

  15. A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

    Directory of Open Access Journals (Sweden)

    C.M. Szobot

    2008-03-01

    Full Text Available Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS on attention-deficit/hyperactivity disorder (ADHD symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD. Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo or group B (reverse order. The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV and the Clinical Global Impression Scale (CGI. We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100% and cocaine users (N = 7; 43.8%. Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001. MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

  16. PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

    NARCIS (Netherlands)

    GRINYO, J; GROTH, C; PICHLMAYR, R; SADEK, SA; VANRENTERGHEM, Y; BEHREND, M; LUCK, R; MORESO, F; PEETERS, J; RODICIO, J; MORALES, J; ALBRECHTSEN, D; FAUCHALD, P; SADEK, S; LODGE, J; SOULILLOU, JP; CANTAROVICH, D; van Son, W; Tegzess, Adam; WAGNER, K; ERHARD, J; BRATTSTROM, C; MJORNSTEDT, L; WIESEL, M; CARL, S; NEUMAYER, HH; HAUSER, [No Value; LANG, P; BOURGEON, B; TUFVESON, G; GANNEDAHL, G; EKBERG, H; PERSSON, N; TARANTINO, A; CAMPISE, M; THIEL, G; ZEILER, M; HENE, R; LIGTENBERG, G; MORGAN, A; RIGG, K; HOOFTMAN, L; HUTCHINSON, K

    1995-01-01

    Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with

  17. A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold.

    Science.gov (United States)

    Dockhorn, R; Grossman, J; Posner, M; Zinny, M; Tinkleman, D

    1992-12-01

    Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003).

  18. Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Foster, David J R; Upton, Richard N

    2014-01-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine...... in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed......, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described....

  19. The effect of Vaccinium uliginosum extract on tablet computer-induced asthenopia: randomized placebo-controlled study.

    Science.gov (United States)

    Park, Choul Yong; Gu, Namyi; Lim, Chi-Yeon; Oh, Jong-Hyun; Chang, Minwook; Kim, Martha; Rhee, Moo-Yong

    2016-08-18

    To investigate the alleviation effect of Vaccinium uliginosum extract (DA9301) on tablet computer-induced asthenopia. This was a randomized, placebo-controlled, double-blind and parallel study (Trial registration number: 2013-95). A total 60 volunteers were randomized into DA9301 (n = 30) and control (n = 30) groups. The DA9301 group received DA9301 oral pill (1000 mg/day) for 4 weeks and the control group received placebo. Asthenopia was evaluated by administering a questionnaire containing 10 questions (responses were scored on a scales of 0-6; total score: 60) regarding ocular symptoms before (baseline) and 4 weeks after receiving pills (DA9301 or placebo). The participants completed the questionnaire before and after tablet computer (iPad Air, Apple Inc.) watching at each visit. The change in total asthenopia score (TAS) was calculated and compared between the groups TAS increased significantly after tablet computer watching at baseline in DA9301 group. (from 20.35 to 23.88; p = 0.031) However, after receiving DA9301 for 4 weeks, TAS remained stable after tablet computer watching. In the control group, TAS changes induced by tablet computer watching were not significant both at baseline and at 4 weeks after receiving placebo. Further analysis revealed the scores for "tired eyes" (p = 0.001), "sore/aching eyes" (p = 0.038), "irritated eyes" (p = 0.010), "watery eyes" (p = 0.005), "dry eyes" (p = 0.003), "eye strain" (p = 0.006), "blurred vision" (p = 0.034), and "visual discomfort" (p = 0.018) significantly improved in the DA9301 group. We found that oral intake of DA9301 (1000 mg/day for 4 weeks) was effective in alleviating asthenopia symptoms induced by tablet computer watching. The study is registered at www.clinicaltrials.gov (registration number: NCT02641470, date of registration December 30, 2015).

  20. Test Equality between Three Treatments under an Incomplete Block Crossover Design.

    Science.gov (United States)

    Lui, Kung-Jong

    2015-01-01

    Under a random effects linear additive risk model, we compare two experimental treatments with a placebo in continuous data under an incomplete block crossover trial. We develop three test procedures for simultaneously testing equality between two experimental treatments and a placebo, as well as interval estimators for the mean difference between treatments. We apply Monte Carlo simulations to evaluate the performance of these test procedures and interval estimators in a variety of situations. We note that the bivariate test procedure accounting for the dependence structure based on the F-test is preferable to the other two procedures when there is only one of the two experimental treatments has a non-zero effect vs. the placebo. We note further that when the effects of the two experimental treatments vs. a placebo are in the same relative directions and are approximately of equal magnitude, the summary test procedure based on a simple average of two weighted-least-squares (WLS) estimators can outperform the other two procedures with respect to power. When one of the two experimental treatments has a relatively large effect vs. the placebo, the univariate test procedure with using Bonferroni's equality can be still of use. Finally, we use the data about the forced expiratory volume in 1 s (FEV1) readings taken from a double-blind crossover trial comparing two different doses of formoterol with a placebo to illustrate the use of test procedures and interval estimators proposed here.

  1. A randomized, double-blind, placebo-controlled study of escitalopram in patients with social anxiety disorder in Japan.

    Science.gov (United States)

    Asakura, Satoshi; Hayano, Taiji; Hagino, Atsushi; Koyama, Tsukasa

    2016-01-01

    This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). Patients aged 18-64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. This study has the www.japic.or.jp identifier: JapicCTI-121842. For the primary efficacy endpoint, the difference from placebo in the LSAS-J was -3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of -9.8 (p escitalopram 10 mg) and -10.1 (p escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics.

  2. Randomized, Placebo-Controlled, Double-Blind Pilot Study of D-Cycloserine in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Andrew J. Butler

    2015-01-01

    Full Text Available Stroke is a leading cause of death and disability in the USA. Up to 60% of patients do not fully recover despite intensive physical therapy treatment. N-Methyl-D-aspartate receptors (NMDA-R have been shown to play a role in synaptic plasticity when activated. D-Cycloserine promotes NMDA receptor function by binding to receptors with unoccupied glycine sites. These receptors are involved in learning and memory. We hypothesized that D-cycloserine, when combined with robotic-assisted physiotherapy (RAP, would result in greater gains compared with placebo + RAP in stroke survivors. Participants (n=14 were randomized to D-cycloserine plus RAP or placebo plus RAP. Functional, cognitive, and quality-of-life measures were used to assess recovery. There was significant improvement in grip strength of the affected hand within both groups from baseline to 3 weeks (95% confidence interval for mean change, 3.95 ± 2.96 to 4.90 ± 3.56 N for D-cycloserine and 5.72 ± 3.98 to 8.44 ± 4.90 N for control. SIS mood domain showed improvement for both groups (95% confidence interval for mean change, 72.6 ± 16.3 to 82.9 ± 10.9 for D-cycloserine and 82.9 ± 13.5 to 90.3 ± 9.9 for control. This preliminary study does not provide evidence that D-cycloserine can provide greater gains in learning compared with placebo for stroke survivors.

  3. Does EEG-Neurofeedback Improve Neurocognitive Functioning in Children with Attention-Deficit/Hyperactivity Disorder? A Systematic Review and a Double-Blind Placebo-Controlled Study

    Science.gov (United States)

    Vollebregt, Madelon A.; van Dongen-Boomsma, Martine; Buitelaar, Jan K.; Slaats-Willemse, Dorine

    2014-01-01

    Background: The number of placebo-controlled randomized studies relating to EEG-neurofeedback and its effect on neurocognition in attention-deficient/hyperactivity disorder (ADHD) is limited. For this reason, a double blind, randomized, placebo-controlled study was designed to assess the effects of EEG-neurofeedback on neurocognitive functioning…

  4. Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

    Science.gov (United States)

    Elberling, J; Duus Johansen, J; Dirksen, A; Mosbech, H

    2006-08-01

    Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

  5. Effect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Coles Leah T

    2012-12-01

    Full Text Available Abstract Background The consumption of beetroot juice on a low nitrate diet may lower blood pressure (BP and therefore reduce the risk of cardiovascular events. However, it is unknown if its inclusion as part of a normal diet has a similar effect on BP. The aim of the study was to conduct a randomized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP. Method Fifteen women and fifteen men participated in a double-blind, randomized, placebo-controlled, crossover study. Volunteers were randomized to receive 500 g of beetroot and apple juice (BJ or a placebo juice (PL. Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor (ABPM. Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities. The identical procedure was repeated 2-wk later with the drink (BJ or PL not consumed on the first visit. Results Overall, there was a trend (P=0.064 to lower systolic blood pressure (SBP at 6-h after drinking BJ relative to PL. Analysis in men only (n=13 after adjustment for baseline differences demonstrated a significant (P Conclusions Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults. Trial registration anzctr.org.au ACTRN12612000445875

  6. A Link between Meiotic Prophase Progression and CrossoverControl

    Energy Technology Data Exchange (ETDEWEB)

    Carlton, Peter M.; Farruggio, Alfonso P.; Dernburg, Abby F.

    2005-07-06

    During meiosis, most organisms ensure that homologous chromosomes undergo at least one exchange of DNA, or crossover, to link chromosomes together and accomplish proper segregation. How each chromosome receives a minimum of one crossover is unknown. During early meiosis in Caenorhabditis elegans and many other species, chromosomes adopt a polarized organization within the nucleus, which normally disappears upon completion of homolog synapsis. Mutations that impair synapsis even between a single pair of chromosomes in C. elegans delay this nuclear reorganization. We quantified this delay by developing a classification scheme for discrete stages of meiosis. Immunofluorescence localization of RAD-51 protein revealed that delayed meiotic cells also contained persistent recombination intermediates. Through genetic analysis, we found that this cytological delay in meiotic progression requires double-strand breaks and the function of the crossover-promoting heteroduplex HIM-14 (Msh4) and MSH-5. Failure of X chromosome synapsis also resulted in impaired crossover control on autosomes, which may result from greater numbers and persistence of recombination intermediates in the delayed nuclei. We conclude that maturation of recombination events on chromosomes promotes meiotic progression, and is coupled to the regulation of crossover number and placement. Our results have broad implications for the interpretation of meiotic mutants, as we have shown that asynapsis of a single chromosome pair can exert global effects on meiotic progression and recombination frequency.

  7. Effectiveness of tamsulosin in prevention of post-operative urinary retention: a randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Madani, Ali Hamidi; Aval, Hamidreza Baghani; Mokhtari, Gholamreza; Nasseh, Hamidreza; Esmaeili, Samaneh; Shakiba, Maryam; Shakiba, Reza Shahrokhi; Seyed Damavand, Seyed Mohamad

    2014-01-01

    Urinary retention is one of the most common complications contributing to surgical procedures. Recent studies have shown the benefits of alpha-adrenergic blockers in preventing post-operative urinary retention (POUR). The aim of this prospective study was to compare the prophylactic effect of tamsulosin with placebo on postoperative urinary retention. In this randomized placebo controlled, clinical trial, 232 male patients aged 18 to 50 years old admitted to Razi University Hospital for varicocelectomy, inguinal herniorrhaphy, and scrotal surgery were randomly assigned to receive either three doses of 0.4mg tamsulosin (n = 118) or placebo (n = 114), 14 and 2 hours before, and 10 hours after surgery. Patients were closely monitored for the development of urinary retention 24 hours after surgical intervention. The primary endpoint was to investigate the effect of tamsulosin in prevention of post-operative urinary retention during the first 24 hours after surgical intervention. Collected data were analyzed using SPSS software version 18 and the P tamsulosin arm and 114 in placebo arm. POUR in patients who received tamsulosin was significantly lower than placebo, as 5.9% of the patients treated with tamsulosin and 21.1% placebo group, reported urinary retention following surgery (P = 0.001). No serious adverse effects were seen in both groups. This study suggests that short perioperative treatment with tamsulosin can reduce the incidence of urinary retention and the need for catheterization after varicocelectomy, inguinal herniorrhaphy, and scrotal surgery.

  8. Double-blind, placebo-controlled food challenge with apple

    DEFF Research Database (Denmark)

    Skamstrup Hansen, K; Vestergaard, H; Stahl Skov, P

    2001-01-01

    The aim of the study was to develop and evaluate different methods of double-blind, placebo-controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, and freeze-dried apple powder. All challenges were performed outside...... frequency of reactions to placebo, probably due to the ingredients used for blinding. The sensitivity of the models with freshly grated apple and freeze-dried apple powder was 0.74/0.60. An increase in sensitivity is desirable. The freeze-dried apple powder proved to be useful for SPT, HR, and oral...

  9. Developing a placebo-controlled trial in surgery: issues of design, acceptability and feasibility.

    Science.gov (United States)

    Campbell, M K; Entwistle, V A; Cuthbertson, B H; Skea, Z C; Sutherland, A G; McDonald, A M; Norrie, J D; Carlson, R V; Bridgman, S

    2011-02-21

    Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this

  10. Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

    Directory of Open Access Journals (Sweden)

    McDonald AM

    2011-02-01

    Full Text Available Abstract Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons; plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists; three focus groups with anaesthetists (one national, two regional; 58 anaesthetists; two focus groups with members of the patient organisation Arthritis Care (7 participants; telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants; interviews with Chairs of UK ethics committees (6 individuals; postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists; two centre pilot (49 patients assessed. Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions proved easier than the method of anaesthesia (general anaesthesia. General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about

  11. Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Shah Gaurang R

    2012-09-01

    Full Text Available Abstract Background Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP – a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. Methods 78 men aged 25–50 years of age; suffering from mild to moderate erectile dysfunction (ED, participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS, Serum testosterone, Semen analysis, Investigator’s Global assessment and Subjects’ opinion. Results In subjects receiving VXP, the IIEF-Erectile Function (EF scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd IIEF-EF score at baseline increased from 16.08 (2.87 to 25.08 (4.56 in the VXP group versus 15.86 (3.24 to 16.47 (4.25 in the placebo group (P P  Conclusions VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Trial Registration Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009

  12. The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Chen, Xi; Zou, Kun; Abdullah, Natasya; Whiteside, Nicola; Sarmanova, Aliya; Doherty, Michael; Zhang, Weiya

    2017-07-01

    The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.

  13. [A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954].

    Science.gov (United States)

    Häßler, Frank; Weirich, Steffen

    2017-09-01

    A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954 Glutamic acid was commonly used in the treatment of intellectually disabled children in the 50s. Koch reported first results of an observation of 140 children treated with glutamic acid in 1952. In this line is the multi-arm placebo-controlled study reported here. The original study protocols were available. 58 children with speech problems who attending a school of special needs received glutamic acid, or vitamin B, or St.-John's-wort. The effect of glutamic acid was in few cases an improvement of attention. On the other hand restlessness and stutter increased. The majority of all reported a weight loss. The treatment with vitamin B showed a positive effect concerning concentration. The treatment with St.-John's wort was stopped caused by headache and vomiting in eight of nine cases. The results of the study reported here are unpublished. The reason may be that until the 60s the effects of glutamic acid in the treatment of intellectually disabled children were in generally overestimated.

  14. Effects of smartphone use with and without blue light at night in healthy adults: A randomized, double-blind, cross-over, placebo-controlled comparison.

    Science.gov (United States)

    Heo, Jung-Yoon; Kim, Kiwon; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Kim, Min-Ji; Kim, Dong Jun; Chang, Kyung-Ah Judy; Oh, Yunhye; Yu, Bum-Hee; Jeon, Hong Jin

    2017-04-01

    Smartphones deliver light to users through Light Emitting Diode (LED) displays. Blue light is the most potent wavelength for sleep and mood. This study investigated the immediate effects of smartphone blue light LED on humans at night. We investigated changes in serum melatonin levels, cortisol levels, body temperature, and psychiatric measures with a randomized, double-blind, cross-over, placebo-controlled design of two 3-day admissions. Each subject played smartphone games with either conventional LED or suppressed blue light from 7:30 to 10:00PM (150 min). Then, they were readmitted and conducted the same procedure with the other type of smartphone. Serum melatonin levels were measured in 60-min intervals before, during and after use of the smartphones. Serum cortisol levels and body temperature were monitored every 120 min. The Profile of Mood States (POMS), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and auditory and visual Continuous Performance Tests (CPTs) were administered. Among the 22 participants who were each admitted twice, use of blue light smartphones was associated with significantly decreased sleepiness (Cohen's d = 0.49, Z = 43.50, p = 0.04) and confusion-bewilderment (Cohen's d = 0.53, Z = 39.00, p = 0.02), and increased commission error (Cohen's d = -0.59, t = -2.64, p = 0.02). Also, users of blue light smartphones experienced a longer time to reach dim light melatonin onset 50% (2.94 vs. 2.70 h) and had increases in body temperature, serum melatonin levels, and cortisol levels, although these changes were not statistically significant. Use of blue light LED smartphones at night may negatively influence sleep and commission errors, while it may not be enough to lead to significant changes in serum melatonin and cortisol levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study

    Science.gov (United States)

    2014-01-01

    Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Results Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted. PMID:24773615

  16. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study.

    Science.gov (United States)

    Akhtari, Elham; Raisi, Firoozeh; Keshavarz, Mansoor; Hosseini, Hamed; Sohrabvand, Farnaz; Bioos, Soodabeh; Kamalinejad, Mohammad; Ghobadi, Ali

    2014-04-28

    Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.

  17. Pregabalin for anxiety in patients with schizophrenia - A randomized, double-blind placebo-controlled study

    DEFF Research Database (Denmark)

    Schjerning, Ole; Damkier, Per; Lykkegaard, Signe Engelhardt

    2017-01-01

    INTRODUCTION: Anxiety is frequent in patients with schizophrenia and poses a major impact on patients perceived quality of life, daily functioning and risk of suicide. Pregabalin has shown effective in the treatment of generalized anxiety disorder and has been suggested for the treatment of anxiety...... in patients with schizophrenia. As evidence is sparse regarding treatment of anxiety in this patient group, we aimed to investigate the use of pregabalin for anxiety in patients with schizophrenia. METHODS: A randomized, double-blind placebo controlled study was used. Patients were randomized to either...... placebo or pregabalin (≤600mg/d) as add-on treatment. Primary analyses were intention-to-treat based with change in Hamilton Anxiety Scale after 4 and 8weeks of treatment as primary outcome. Secondary outcomes were change in psychopathology, quality-of-life, cognitive functioning and sleep. The study used...

  18. Placebo-controlled study of fluvoxamine in the treatment of patients with compulsive buying.

    Science.gov (United States)

    Ninan, P T; McElroy, S L; Kane, C P; Knight, B T; Casuto, L S; Rose, S E; Marsteller, F A; Nemeroff, C B

    2000-06-01

    Compulsive buying is a syndrome characterized by the impulsive and/or compulsive buying of unneeded objects that results in personal distress, impairment in vocational or social functioning, and/or financial problems. Results from a two-site, double-blind, placebo-controlled 13-week trial of fluvoxamine are presented. Subjects had problematic buying behavior that they could not control for the previous 6 months or longer and met DSM-IV criteria for impulse control disorder-not otherwise specified (ICD-NOS) and the University of Cincinnati criteria for compulsive buying. Assessments included clinician-rated scales-the Yale-Brown Obsessive Compulsive Scale modified for compulsive buying, the Clinical Global Impression Scale, the Global Assessment of Functioning, and the Hamilton Rating Scale for Depression-and patient self-reports using daily diaries, which measured episodes of compulsive buying. Forty-two subjects gave informed consent, with 37 subjects providing evaluable information and 23 completing the study. Current or past psychiatric comorbidity was present in 74% of subjects. Intent-to-treat and completer analyses failed to show a significant difference between treatments on any measures of outcome. A high placebo-response rate, possibly from the behavioral benefits of maintaining a daily diary, prevents any definitive statement on the efficacy of fluvoxamine in treating compulsive buying.

  19. Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

    Science.gov (United States)

    Shah, Gaurang R; Chaudhari, Manojkumar V; Patankar, Suresh B; Pensalwar, Shrikant V; Sabale, Vilas P; Sonawane, Navneet A

    2012-09-15

    Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

  20. Effect of aromatherapy massage on menopausal symptoms: a randomized placebo-controlled clinical trial.

    Science.gov (United States)

    Darsareh, Fatemeh; Taavoni, Simin; Joolaee, Soodabeh; Haghani, Hamid

    2012-09-01

    Menopause is a significant event in most women's lives because it marks the end of a woman's natural reproductive life. The purpose of this study was to determine the effect of aromatherapy massage on menopausal symptoms. A randomized placebo-controlled clinical trial was conducted at a menopausal clinic at a gynecology hospital in Tehran. The study population comprised 90 women who were assigned to an aromatherapy massage group, a placebo massage group, or a control group. Each participant in the aromatherapy massage group received 30-minute aromatherapy treatment sessions twice a week for 4 weeks with aroma oil, whereas participants in the placebo massage group received the same treatment with plain oil. No treatment was provided to participants in the control group. The outcome measures in this study were menopausal symptoms, as obtained through the Menopause Rating Scale. The mean baseline level of the menopausal score did not differ among all groups. However, after eight sessions of intervention, the Menopause Rating Scale score differed significantly among the three groups (P aromatherapy massage group and the placebo massage group had a lower menopausal score than the control group (P aromatherapy massage and the placebo massage groups were compared, the menopausal score for the aromatherapy massage group was found to be significantly lower (P aromatherapy massage were effective in reducing menopausal symptoms. However, aromatherapy massage was more effective than only massage.

  1. The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

    Science.gov (United States)

    Leather, A T; Studd, J W; Watson, N R; Holland, E F

    1999-02-01

    The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

  2. Effect of Persian Medicine Remedy on Chemotherapy Induced Nausea and Vomiting in Breast Cancer: A Double Blind, Randomized, Crossover Clinical Trial

    Science.gov (United States)

    Nazari, Mohammad; Taghizadeh, Ali; Bazzaz, Mojtaba Mousavi; Rakhshandeh, Hassan; Shokri, Sadegh

    2017-01-01

    Background Chemotherapy induced nausea and vomiting (CINV) is a side effect, and has negative effect on quality of life and continuation of chemotherapy. Despite new regimen and drugs, the problems still remain and standard guidelines, effective treatment and supportive care for refractory CINV are still not yet established. Persian medicine, the old Iranian medical school, offer Persumac (prepared from Rhus Coriaria and Bunium Persicum Boiss). Objective The specific objectives were to assess the effect of Persumac on the number and severity of nausea and vomiting in refractory CINV in acute and delayed phase. Methods This randomized, double blind, crossover clinical trial study was carried out on 93 patients with breast cancer and refractory CINV, who received outpatient high emetogenic chemotherapy in Imam Reza hospital, Mashhad, Iran from October 2015 to May 2016. The study has three stages: in stage I patients received a questionaire and completed it after chemotherapy. In stage II they were randomly divided into intervention group with Persumac and control group with placebo (lactose were used). In stage III, wash out and crossover was conducted. Both groups in all stages received standard antiemetic therapy for CINV. The following were set as the inclusion criteria of the study: female, Age ≥18 years, clinical diagnosis of breast cancer, history of refractory CINV, normal blood tests and at least three courses of chemotherapy remaining. Exclusion criteria of this study were: Total or upper abdominal radiation therapy along with chemotherapy, drugs/therapy for nausea and vomiting not prescribed in this study, hypersensitivity to Sumac or Bunium Persicum, use of sumac and Bunium Persicum in seven days prior to the intervention, clinical diagnosis of digestion disorders, non-chemotherapy induced nausea and vomiting, milk allergy, loss of two consecutive or three intermittent doses of Persumac or placebo. Outcomes were gathered by Persian questionnaire. Number

  3. Effectiveness of tamsulosin in prevention of post-operative urinary retention: a randomized double-blind placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Ali Hamidi Madani

    2014-01-01

    Full Text Available Purpose: Urinary retention is one of the most common complications contributing to surgical procedures. Recent studies have shown the benefits of alpha-adrenergic blockers in preventing post-operative urinary retention (POUR. The aim of this prospective study was to compare the prophylactic effect of tamsulosin with placebo on postoperative urinary retention. Materials and Methods: In this randomized placebo controlled, clinical trial, 232 male patients aged 18 to 50 years old admitted to Razi University Hospital for varicocelectomy, inguinal herniorrhaphy, and scrotal surgery were randomly assigned to receive either three doses of 0.4mg tamsulosin (n = 118 or placebo (n = 114, 14 and 2 hours before, and 10 hours after surgery. Patients were closely monitored for the development of urinary retention 24 hours after surgical intervention. The primary endpoint was to investigate the effect of tamsulosin in prevention of post-operative urinary retention during the first 24 hours after surgical intervention. Collected data were analyzed using SPSS software version 18 and the P < 0.05 was considered statistically significant. Results: One hundred and eighteen patients were included in tamsulosin arm and 114 in placebo arm. POUR in patients who received tamsulosin was significantly lower than placebo, as 5.9% of the patients treated with tamsulosin and 21.1% placebo group, reported urinary retention following surgery (P = 0.001. No serious adverse effects were seen in both groups. Conclusions: This study suggests that short perioperative treatment with tamsulosin can reduce the incidence of urinary retention and the need for catheterization after varicocelectomy, inguinal herniorrhaphy, and scrotal surgery.

  4. Renal Hemodynamic Effects of Serelaxin in Patients With Chronic Heart Failure A Randomized, Placebo-Controlled Study

    NARCIS (Netherlands)

    Voors, Adriaan A.; Dahlke, Marion; Meyer, Sven; Stepinska, Janina; Gottlieb, Stephen S.; Jones, Andrew; Zhang, Yiming; Laurent, Didier; Slart, Riemer H. J. A.; Navis, Gerjan J.

    2014-01-01

    Background-Serelaxin is a promising therapy for acute heart failure. The renal hemodynamic effects of serelaxin in patients with chronic heart failure are unknown. Methods and Results-In this double-blind, randomized, placebo-controlled, multicenter study, patients with New York Heart Association

  5. Lactobacillus reuteri strain combination in Helicobacter pylori infection: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Francavilla, Ruggiero; Polimeno, Lorenzo; Demichina, Antonella; Maurogiovanni, Giovanni; Principi, Beatrice; Scaccianoce, Giuseppe; Ierardi, Enzo; Russo, Francesco; Riezzo, Giuseppe; Di Leo, Alfredo; Cavallo, Luciano; Francavilla, Antonio; Versalovic, James

    2014-01-01

    The goals of this study were to investigate the role of a new probiotic preparation (Lactobacillus reuteri DSM 17938 and L. reuteri ATCC PTA 6475) in Helicobacter pylori infection. Specific probiotic strains play a role in H. pylori infection for their ability to decrease bacterial load and gastritis, prevent antibiotic-associated side effects, and increase the eradication rate. This is a prospective, double-blind, randomized, placebo-controlled study in a tertiary care setting. A total of 100 H. pylori-positive naive patients received either L. reuteri combination (2×10 Colony Forming Units) or placebo during a 3-phase study (pre-eradication, eradication, and follow-up). All underwent C urea breath test (C-UBT), blood assessments of gastrin-17 (G17), endoscopy, and the Gastrointestinal Symptom Rating Scale. Eradication was confirmed by C-UBT 8 weeks after the completion of therapy. Fifty patients were allocated in each group. During pre-eradication period, C-UBT δ decreased by 13% in L. reuteri combination as compared with a 4% increase in placebo (-13.2±34% vs. 4.3±27%; Preuteri combination (6.8±2.9 vs. 4±3.1; Preuteri combination as compared with placebo-reported side effects (40.9% vs. 62.8%; Preuteri combination (28% vs. 12%; Preuteri combination and 65.9% in placebo (P=NS). L. reuteri combination increased eradication rate by 9.1% (odds ratio: 1.5). L. reuteri combination alone is able to exert an inhibitory effect on H. pylori growth, and when administered with eradication therapy, it determines a significant reduction in antibiotic-associated side effects. Moreover, L. reuteri combination was able to decrease serum G17 levels and to (not significantly) increase the H. pylori-eradication rate.

  6. Ethical Overview of Placebo Control in Psychiatric Research - Concepts and Challenges.

    Science.gov (United States)

    Ćurković, Marko; Živković, Maja; Radić, Krešimir; Vilibić, Maja; Ćelić, Ivan; Bagarić, Dario

    2015-06-01

    Permissibility of placebo controls in psychiatric research is raising everlasting controversies. The main ethical issue remains: whether, when, under what conditions, and to what extent is it justifiable to disregard subject's present (best) interest for the presumably "greater" ones. In relation to this main ethical concern, two distinct arguments arose: proponents of placebo controls trials (placebo ortxodoxy) and proponents of active controls trials (active-control orthodoxy). More recently, in new ethical guidelines, Declaration of Helsinki and International Ethical Guidelines for Biomedical Research Involving Human Subjects, a "middle way" approach was formulated, acceptable to both sides of the argument, saying placebo controls can be justified under certain conditions: when and only when, they firstly present undisputed methodological reasoning, and secondly, fulfill certain ethical considerations - mainly regarding the permissibility of accompanied risks. These ethical evaluations are inevitably contextual and evoke the need for the principle of proportionality. In scope of recent findings of substantial and progressively increasing placebo response in psychiatric research, contextual factors are identified and both theoretical and practical challenges are discussed.

  7. Short-Term Effects of Methylphenidate on Math Productivity in Children With Attention-Deficit/Hyperactivity Disorder are Mediated by Symptom Improvements: Evidence From a Placebo-Controlled Trial.

    Science.gov (United States)

    Kortekaas-Rijlaarsdam, Anne Fleur; Luman, Marjolein; Sonuga-Barke, Edmund; Bet, Pierre M; Oosterlaan, Jaap

    2017-04-01

    Although numerous studies report positive effects of methylphenidate on academic performance, the mechanism behind these improvements remains unclear. This study investigates the effects of methylphenidate on academic performance in children with attention-deficit/hyperactivity disorder (ADHD) and the mediating and moderating influence of ADHD severity, academic performance, and ADHD symptom improvement. Sixty-three children with ADHD participated in a double-blind placebo-controlled crossover study comparing the effects of long-acting methylphenidate and placebo. Dependent variables were math, reading, and spelling performance. The ADHD group performance was compared with a group of 67 typically developing children. Methylphenidate improved math productivity and accuracy in children with ADHD. The effect of methylphenidate on math productivity was partly explained by parent-rated symptom improvement, with greater efficacy for children showing more symptom improvement. Further, children showing below-average math performance while on placebo profited more from methylphenidate than children showing above-average math performance. The results from this study indicate positive effects of methylphenidate on academic performance, although these were limited to math abilities. In light of these results, expectations of parents, teachers, and treating physicians about the immediate effects of methylphenidate on academic improvement should be tempered. Moreover, our results implicate that positive effects of methylphenidate on math performance are in part due directly to effects on math ability and in part due to reductions in ADHD symptoms.

  8. Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.

    Science.gov (United States)

    Mombelli, Andrea; Almaghlouth, Adnan; Cionca, Norbert; Courvoisier, Delphine S; Giannopoulou, Catherine

    2015-03-01

    The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.

  9. Onset of relief of dyspnoea with budesonide/formoterol or salbutamol following methacholine-induced severe bronchoconstriction in adults with asthma: a double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Bantje Theo A

    2006-12-01

    Full Text Available Abstract Background The long-acting β2-agonist (LABA formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma. Methods In this randomised, double-blind, placebo-controlled, cross-over study, 32 patients with asthma underwent a methacholine provocation test leading to a fall in forced expiratory volume in 1 second (FEV1 of ≥30% at enrolment (Visit 1 and three subsequent study visits (Visits 2–4. Immediately after each provocation at Visits 2–4, patients received one of three test treatments: one inhalation of budesonide/formoterol 160/4.5 μg (via Turbuhaler®, two inhalations of salbutamol 100 μg (via a pressurised metered-dose inhaler [pMDI] or placebo. All patients received each of the test treatments in a randomised order, after separate methacholine provocations. The effect of treatment on FEV1 and breathlessness (using the Borg scale was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment. Results Following methacholine provocation, Borg score increased from a baseline value of below 0.5 to 3.03, 3.31 and 3.50 before treatment with budesonide/formoterol, salbutamol and placebo, respectively. Budesonide/formoterol and salbutamol reversed methacholine-induced dyspnoea (breathlessness rapidly. At 1 minute after inhalation, statistically significant decreases in Borg score were observed for budesonide/formoterol and salbutamol (p = 0.0233 and p 1 (both active treatments p Conclusion Single doses of budesonide/formoterol and salbutamol both provided rapid relief of dyspnoea and reversal of severe airway obstruction in patients with asthma with experimentally induced bronchoconstriction. The

  10. On Suggestibility and Placebo: A Follow-Up Study.

    Science.gov (United States)

    Lifshitz, Michael; Sheiner, Eli O; Olson, Jay A; Thériault, Rémi; Raz, Amir

    2017-04-01

    Identifying what makes some people respond well to placebos remains a major challenge. Here, we attempt to replicate an earlier study in which we found a relationship between hypnotic suggestibility and subjective ratings of relaxation following the ingestion of a placebo sedative (Sheiner, Lifshitz, & Raz, 2016). To assess the reliability of this effect, we tested 34 participants using a similar design. Participants ingested a placebo capsule in one of two conditions: (1) relaxation, wherein we described the capsule as a herbal sedative, or (2) control, wherein we described the capsule as inert. To index placebo response, we collected measures of blood pressure and heart rate, as well as self-report ratings of relaxation and drowsiness. Despite using a similar experimental design as in our earlier study, we were unable to replicate the correlation between hypnotic suggestibility and placebo response. Furthermore, whereas in our former experiment we observed a change in subjective ratings of relaxation but no change in physiological measures, here we found that heart rate dropped in the relaxation condition while subjective ratings remained unchanged. Even within a consistent context of relaxation, therefore, our present results indicate that placebos may induce effects that are fickle, tenuous, and unreliable. Although we had low statistical power, our findings tentatively accord with the notion that placebo response likely involves a complex, multifaceted interaction between traits, expectancies, and contexts.

  11. A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.

    Directory of Open Access Journals (Sweden)

    Jordan E Bisanz

    Full Text Available A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains.ClinicalTrials.gov NCT02139839.

  12. Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study.

    NARCIS (Netherlands)

    Michelson, D.; Danckaerts, M.; Gillberg, C.; Spencer, T.J.; Zuddas, A.; Faries, D.E.; Zhang, S.; Biederman, J.

    2004-01-01

    OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported. METHOD: In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label

  13. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2012-08-01

    Full Text Available Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST, which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland. In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily with placebo-azithromycin; azithromycin (5 mg/kg daily with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management

  14. Catalytic Activity Control via Crossover between Two Different Microstructures

    KAUST Repository

    Zhou, Yuheng; Zhu, Yihan; Wang, Zhi-Qiang; Zou, Shihui; Ma, Guicen; Xia, Ming; Kong, Xueqian; Xiao, Liping; Gong, Xue-Qing; Fan, Jie

    2017-01-01

    microstructural control through the crossover between multiply-twinned nanoparticle (MTP) and single crystal (SC) can be readily achieved by solvent post-treatment on gold nanoparticles (AuNPs). Polar solvents (e.g. water, methanol) direct the transformation from

  15. Tinnitus control by dopamine agonist pramipexole in presbycusis patients: a randomized, placebo-controlled, double-blind study.

    Science.gov (United States)

    Sziklai, István; Szilvássy, Judit; Szilvássy, Zoltán

    2011-04-01

    Since the concept of tinnitus dopaminergic pathway emerged, studies have been proposed to investigate if dopaminergic agents influence tinnitus. We hypothesized that pramipexole, an agonist on D2/D3 receptors, may antagonize tinnitus in the presbycusis patients (in the frequency range of 250 to 8,000 Hz) in a dose schedule accepted for the treatment of Parkinson's disease in elderly people. We designed a randomized, prospective, placebo-controlled and double-blind trial. Forty presbycusis patients aged 50 years or older with subjective tinnitus were randomized to two groups (20 patients in both). Patients in the drug group took pramipexole over a period of 4 weeks according to a treatment schedule as follows: week 1, 0.088 mg t.i.d.; week 2, 0.18 mg t.i.d.; week 3, 0.7 mg t.i.d.; week 4, 0.18 mg t.i.d. over 3 days and 0.088 mg t.i.d. the rest of the week. Patients in the second group received placebo. Determination of subjective grading of tinnitus perception, the tinnitus handicap inventory (THI) questionnaire and electrocochleography (ECOG) examinations served as the end points. Subjective audiometry was used to produce secondary data. A significant improvement in tinnitus annoyance is found in the group treated with pramipexole versus placebo with respect to inhibition of tinnitus and a decrease of tinnitus loudness greater than 30 dB. However, neither ECOG nor subjective pure-tone threshold audiometry revealed any change in hearing threshold in response to either pramipexole or placebo. Pramipexole is an effective agent against subjective tinnitus associated with presbycusis at a dose schedule used for the treatment of Parkinson's disease. The drug did not change hearing threshold. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  16. Radon balneotherapy and physical activity for osteoporosis prevention: a randomized, placebo-controlled intervention study.

    Science.gov (United States)

    Winklmayr, Martina; Kluge, Christian; Winklmayr, Wolfgang; Küchenhoff, Helmut; Steiner, Martina; Ritter, Markus; Hartl, Arnulf

    2015-03-01

    Low-dose radon hyperthermia balneo treatment (LDRnHBT) is applied as a traditional measure in the non-pharmacological treatment of rheumatic diseases in Europe. During the last decades, the main approach of LDRnHBT was focused on the treatment of musculoskeletal disorders, but scientific evidence for the biological background of LDRnHBT is weak. Recently, evidence emerged that LDRnHBT influences bone metabolism. We investigated, whether combined LDRnHBT and exercise treatment has an impact on bone metabolism and quality of life in a study population in an age group at risk for developing osteoporosis. This randomized, double-blind, placebo-controlled trial comprised guided hiking tours and hyperthermia treatment in either radon thermal water (LDRnHBT) or radon-free thermal water (PlaceboHBT). Markers of bone metabolism, quality of life and somatic complaints were evaluated. Statistics was performed by linear regression and a linear mixed model analysis. Significant changes over time were observed for most analytes investigated as well as an improvement in self-assessed health in both groups. No significant impact from the LDRnHBT could be observed. After 6 months, the LDRnHBT group showed a slightly stronger reduction of the osteoclast stimulating protein receptor activator of nuclear kB-ligand compared to the PlaceboHBT group, indicating a possible trend. A combined hyperthermia balneo and exercise treatment has significant immediate and long-term effects on regulators of bone metabolism as well as somatic complaints. LDRnHBT and placeboHBT yielded statistically equal outcomes.

  17. The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

    Science.gov (United States)

    Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

    2017-07-01

    Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

  18. Topical tocopherol for treatment of reticular oral lichen planus: a randomized, double-blind, crossover study.

    Science.gov (United States)

    Bacci, C; Vanzo, V; Frigo, A C; Stellini, E; Sbricoli, L; Valente, M

    2017-01-01

    This randomized, double-blind, placebo-controlled crossover study assessed the efficacy of topical tocopherol acetate compared with placebo in easing oral discomfort in patients with reticular oral lichen planus (ROLP). Thirty-four patients with clinically diagnosed and histologically confirmed ROLP were randomly assigned to two groups, which received first one of two treatments (treatment 1 or 2) for a month, then the other (treatment 2 or 1) for another month, with a two-week washout between them. One treatment contained tocopherol acetate and the other only liquid paraffin. The primary outcome was less discomfort, measured on a visual analog scale (VAS). Secondary outcomes were as follows: length of striae measured and photographed at each follow-up; surface area of lesions; and a modified Thongprasom score. No statistically significant differences emerged between the two treatments (1 vs 2) in terms of VAS scores (P > 0.05; 0.8624) or length of striae (P = 0.0883). Significant differences were seen for surface area of lesions (P < 0.05, P = 0.0045) and modified Thongprasom scores (P = 0.0052). The two treatments differed only in terms of the surface area of the lesions and Thongprasom scores, not in VAS scores for discomfort or the length of patients' striae. Topical tocopherol proved effective in the treatment of ROLP. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies

    Science.gov (United States)

    Wang, Yi-lun; Zeng, Chao; Xie, Dong-xing; Yang, Ye; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-hua

    2015-01-01

    Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; pbupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; pbupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

  20. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study.

    Science.gov (United States)

    Schellenberg, R

    2001-01-20

    To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main efficacy variable: change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. Secondary efficacy variables: changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (Pagnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.

  1. Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Mark Lown

    Full Text Available High sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME, may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut.A double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19-59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract.Thirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC (glucose (mmol / L x h for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316, -14.0% (-26.0%, -2.0%; p = 0.022 and -22.0% (-33.9%, -10.0%; p<0.001 respectively. The difference in the pIAUC (insulin (mIU / L x h for half, normal and double dose ME compared with placebo was -9.7% (-25.8%, 6.3%; p = 0.234, -23.8% (-39.9%, -7.8%; p = 0.004 and -24.7% (-40.8%, -8.6%; p = 0.003 respectively. There were no statistically significant differences between any of the 4 groups in the odds of experiencing one or more gastrointestinal symptoms (nausea, abdominal cramping, distension or flatulence.Mulberry leaf extract significantly reduces total blood glucose rise after ingestion of maltodextrin over 120 minutes. The pattern of effect demonstrates a classical dose response curve with

  2. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

    Science.gov (United States)

    Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

  3. EMLA for pain relief during arterial cannulation. A double-blind, placebo-controlled study of a lidocaine-prilocaine cream

    DEFF Research Database (Denmark)

    Nilsson, A; Danielson, K; Engberg, G

    1990-01-01

    The aim of the study was to evaluate the effect of a lidocaine-prilocaine cream (EMLA cream, Astra) in relieving pain during arterial cannulation. The study had a random, double-blind, placebo-controlled design and included altogether 90 patients. All the patients were premedicated with an opioid...... before cannulation. An EMLA application time of 60 minutes was used in 60 patients (30 EMLA/30 placebo) and there was no difference in the pain reaction measured on a visual analogue scale (VAS) or on an observer's verbal scale. The study was extended with a further 30 patients (15 EMLA/15 placebo......) with an application time exceeding 90 minutes. Between these groups pain experience measured by VAS did not show any significant difference although the mean value was lower in the EMLA group. Observer ratings showed a significant (p less than 0.01) difference in distribution towards lower ratings in the EMLA group...

  4. Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

    Directory of Open Access Journals (Sweden)

    van der Woude Hanneke J

    2010-05-01

    Full Text Available Abstract Background The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear. Methods The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1 after inhaling adenosine 5'-monophosphate (AMP, were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours. Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg, formoterol (4.5 μg, salbutamol (2 × 100 μg or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day. Results In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1. Conclusions A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours

  5. A randomized, double-blind, placebo-controlled crossover study of ...

    African Journals Online (AJOL)

    Erectile dysfunction (ED) is one of the major health concerns affects the quality of life among Thai male. The treatment of ED by the first-line drugs is limited to a certain group of patients due to their side effects and costs. Alternative medicine can be beneficial for the treatment of ED. This is a randomized, double-blind, ...

  6. Atomoxetine treatment for nicotine withdrawal: a pilot double-blind, placebo-controlled, fixed-dose study in adult smokers

    Directory of Open Access Journals (Sweden)

    Silverstone Peter H

    2012-03-01

    Full Text Available Abstract Background Many effective treatments for nicotine addiction inhibit noradrenaline reuptake. Three recent studies have suggested that another noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors. Methods The present double-blind, placebo-controlled, fixed-dose study was carried out over 21 days during which administration of 40 mg atomoxetine was compared to placebo in 17 individuals. Of these, nine were randomized to atomoxetine and eight to placebo. Baseline and weekly measurements were made using the Cigarette Dependence Scale (CDS, Cigarette Withdrawal Scale (CWS, Questionnaire of Smoking Urges (QSU, reported number of cigarettes smoked, and salivary cotinine levels. Results The study results showed that all those on placebo completed the study. In marked contrast, of the nine individuals who started on atomoxetine, five dropped out due to side effects. In a completer analysis there were statistically significant differences at 14 and 21 days in several measures between the atomoxetine and placebo groups, including CDS, CWS, QSU, number of cigarettes smoked (decreasing to less than two per day in the treatment group who completed the study, and a trend towards lower mean salivary cotinine levels. However, these differences were not seen in a last observation carried forward (LOCF analysis. Conclusions In summary, this is the first study to examine the use of atomoxetine in non-psychiatric adult smokers for a period of more than 7 days, and the findings suggest that atomoxetine might be a useful treatment for nicotine addiction. However, the dose used in the current study was too high to be tolerated by many adults, and a dose-finding study is required to determine the most appropriate dose for future studies of this potential treatment for smoking cessation.

  7. Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled study

    Science.gov (United States)

    Paris, A; Gonnet, N; Chaussard, C; Belon, P; Rocourt, F; Saragaglia, D; Cracowski, J L

    2008-01-01

    Aims The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. Methods This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18–60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day−1. Results One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day−1 of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. Conclusions The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. What is already known about this subject The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. What this study adds The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH

  8. Effect of rapid weight loss and glutamine supplementation on immunosuppression of combat athletes: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Tritto, Aline C C; Amano, Mariane T; De Cillo, Maria E; Oliveira, Vinicius A; Mendes, Sandro H; Yoshioka, Caroline; Roschel, Hamilton; Camara, Niels Olsen S; Gualano, Bruno; Artioli, Guilherme G

    2018-02-01

    The role of plasma glutamine concentration and glutamine supplementation on immunosuppression was investigated in combat athletes. Twenty-three male athletes were randomly assigned to receive glutamine (21 g/day, n=12) or placebo (ovalbumin, n=11) for 10 days. Six athletes who did not lose weight served as controls. Athletes were assessed 21 days before (-21d), 1 day before (-1d) and 5 days after (+5d) a competition. Weight reduction was similar between glutamine (-8.2%± 4.1%) and placebo (-8.5%±2.4%) and negligible in control (-0.6%±1.4%). In both weight-loss groups, the majority of athletes reported symptoms of upper respiratory symptoms, as assessed by the Wisconsin upper respiratory symptom survey questionnaire. Only two athletes reported symptoms in the control group. Immune cell function remained unchanged throughout the study except for an increase in neutrophil phagocytic activity (placebo: -21d=5,251±2,986; -1d=17,428±22,374; +5d=21,125±21,934; glutamine: -21d=6,096±3,549; -1d=11,029±17,113; +5d=28,186±21,032 FI) and a minor change in monocyte phagocytic activity (placebo: -21d=4,421±3,634; -1d=3,329±6,283; +5d=3,243± 2,553; glutamine: -21d=4,051±3,186; -1d=3,106±2,625; +5d=4,981± 4,598) in both glutamine and placebo after weight loss. Plasma glutamine and cortisol remained unchanged across the study. creatine kinase levels were increased in placebo (-21d=125.2±54.1; -1d=187.2± 73.5; +5d=111.3±59.1 U/L) but not in glutamine (-21d=136.2±58.2; -1d= 168.8±65.0; +5d=129.7±64.0 U/L). Rapid weight loss increased the frequency and severity of infection symptoms, but this was neither associated with plasma glutamine depletion nor counteracted by glutamine supplementation.

  9. Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

    2011-01-01

    Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

  10. Low Intensity laser therapy in patients with burning mouth syndrome: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Norberto Nobuo SUGAYA

    Full Text Available Abstract The aim of this study was to assess the effectiveness of low intensity laser therapy in patients with Burning Mouth Syndrome (BMS. Thirty BMS subjects were randomized into two groups – Laser (LG and Placebo (CG. Seven patients dropped out, leaving 13 patients in LG and 10 patients in CG. Each patient received 4 irradiations (laser or placebo twice a week, for two consecutive weeks (blinded to the type of irradiation received. Infrared laser (AsGaAI irradiations were applied to the affected mucosa in scanning mode, wavelength of 790 nm, output power of 20 mW and fluence of 6 J/cm2. A visual analogue scale (VAS was used to assess the therapeutic effect before and after each irradiation, and at all the control time periods: 7, 14, 30, 60 and 90 days after the last irradiation. One researcher delivered irradiation and another recorded the results. Both researchers were blinded, the first to the results, and the second to the type of radiation applied. The results were categorized according to the percentage of symptom level variation, and showed a statistically better response in LG in only two categories of the control checkpoints (p=0.02; Fisher’s Exact Test. According to the protocol used in this study, low intensity laser therapy is as beneficial to patients with BMS as placebo treatment, indicating a great emotional component of involvement in BMS symptomatology. Nevertheless, there were positive results in some statistical analyses, thus encouraging further research in BMS laser therapy with other irradiation parameters.

  11. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.

    Science.gov (United States)

    Marcus, Ronald N; Owen, Randall; Kamen, Lisa; Manos, George; McQuade, Robert D; Carson, William H; Aman, Michael G

    2009-11-01

    To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these symptoms, were randomized 1:1:1:1 to aripiprazole (5, 10, or 15 mg/day) or placebo in this 8-week double-blind, randomized, placebo-controlled, parallel-group study. Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale (primary efficacy measure) and the clinician-rated Clinical Global Impressions-Improvement score. Safety and tolerability were also assessed. At week 8, all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores (5 mg/day, -12.4; 10 mg/day, -13.2; 15 mg/day, -14.4; versus placebo, -8.4; all p autistic disorder.

  12. A RANDOMIZED CONTROLLED PLACEBO STUDY OF DEXTROSE IONTOPHORESIS VERSUS DEXTROSE PROLOTHERAPY IN CASE OF KNEE OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    Mahmoud Mohamed Ahmed Ewidea

    2015-12-01

    Full Text Available Background: Osteoarthritis is the most common cause of musculoskeletal pain and disability in the knee joint. This study investigated the efficacy of Dextrose iontophoresis versus Dextrose prolotherapy in case of knee osteoarthritis in a randomized, placebo-controlled, double-blinded study. Methods: sixty patients diagnosed mild to moderate osteoarthritis were included in the study. Their age's were45:65 years with mean age 51 ± 3.5 years. Patients were divided randomly into three equal groups, group (Areceived 50 % dextrose iontophoresis, group (B Each patient received three intra-articular injections of dextrose at 1-month intervals in weeks 0, 4, and 8 and group (C received sham iontophoresis. The outcome measurements were Western Ontario and McMaster Universities arthritis index (WOMAC values, knee ROM, and pain severity at rest (seated and in activity (after walking 6 m using the visual analogue scale (VAS were recorded. The patients were evaluated for these parameters before allocated in their groups then after 4, 8, and 24 weeks later. Results: compared to sham group (placebo there were significant improvement of VAS and ROM of iontophoresis group than sham (placebo group (p<0.000. Also there were significant improvement of prolotherapy group than placebo (p<0.006, and 0.02 respectively. Furthermore there was significant improve of iontophoresis group than prolotherapy where p was <0.000 for VAS, ROM and (WOMAC. Conclusion: The results of this study suggested that both dextrose iontophoresis and dextrose prolotherapy may be as useful modalities in treatment of osteoarthritis with better effects of dextrose iontophoresis than prolotherapy.

  13. Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity.

    Science.gov (United States)

    Karlberg, B E; Kågedal, B; Tegler, L; Tolagen, K; Bergman, B

    1976-03-31

    Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions. Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 +/- 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension.

  14. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

    Science.gov (United States)

    Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

    2015-01-01

    Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

  15. Adverse Events of Atomoxetine in a Double-Blind Placebo-Controlled Study in Children with Autism.

    Science.gov (United States)

    Tumuluru, Rameshwari V; Corbett-Dick, Patricia; Aman, Michael G; Smith, Tristram; Arnold, L Eugene; Pan, Xueliang; Buchan-Page, Kristin A; Brown, Nicole V; Ryan, Melissa M; Hyman, Susan L; Hellings, Jessica; Williams, Craig; Hollway, Jill A; Lecavalier, Luc; Rice, Robert R; McAuliffe-Bellin, Sarah; Handen, Benjamin L

    2017-10-01

    Attention-deficit/hyperactivity disorder (ADHD) symptoms, including inattention and over activity, occur in approximately one-third of children with autism spectrum disorder (ASD). We describe the rate and duration of adverse events in a randomized controlled trial of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance in children with ASD. We conducted a 10-week, double-blind, 2 × 2 trial of ATX and PT with 128 children (ages 5-14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6 weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8 mg/(kg·day) and maintained for an additional 4 weeks. An average of seven PT sessions were conducted in the two PT arms. Adverse events (AEs) were assessed through parent ratings of common symptoms on a seven-point Likert severity scale and through direct interviews with study medical staff. ATX was associated with decreased appetite and fatigue, but was otherwise well tolerated. Most reported AEs lasted 4 weeks or less. Unlike reports with typically developing (TD) children, there were no concerns with QTc changes or suicidal ideation. This study extends the findings of previous studies of ATX in ASD by documenting that the type of AEs was similar to that of TD children, with no significant safety concerns.

  16. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

    Directory of Open Access Journals (Sweden)

    Uri Hertz

    Full Text Available Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

  17. A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

    Science.gov (United States)

    Pecknold, J; Luthe, L; Munjack, D; Alexander, P

    1994-10-01

    This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

  18. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

    Directory of Open Access Journals (Sweden)

    Chetna Deep Lamba

    2018-01-01

    Full Text Available Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ. Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling the eligibility criteria were enrolled (n = 60 and randomised to either the homoeopathic intervention (HI (n = 30 or identical placebo (P (n = 30 with uniform lifestyle modification (LSM for 6 months. Results: The menstrual regularity with improvement in other signs/symptoms was observed in 60% of the cases (n = 18 in HI + LSM group and none (n = 0 in control group (P = 0.001. Statistically significant difference (P = 0.016 was observed in reduction of intermenstrual duration (from 76.1 ± 37.7 to 46.6 ± 38.7 days in HI + LSM in comparison to placebo + LSM group (from 93.0 ± 65.2 to 93.9 ± 96.2 days. In PCOSQ, also, significant improvement was observed in HI group in domains of weight, fertility, emotions and menstrual problems (P < 0.05 with no difference in body hair (P = 0.708. No change was observed in respect of improvement in the ultrasound findings. Pulsatilla was the most frequently indicated medicine (n = 12, 40%. Conclusion: HI along with LSM has shown promising outcome; further comparative study with standard conventional treatment on adequate sample size is desirable.

  19. Acute effect of topical menthol on chronic pain in slaughterhouse workers with carpal tunnel syndrome: triple-blind, randomized placebo-controlled trial

    DEFF Research Database (Denmark)

    Sundstrup, Emil; Jakobsen, Markus Due; Brandt, Mikkel

    2014-01-01

    Topical menthol gels are classified "topical analgesics" and are claimed to relieve minor aches and pains of the musculoskeletal system. In this study we investigate the acute effect of topical menthol on carpal tunnel syndrome (CTS). We screened 645 slaughterhouse workers and recruited 10...... participants with CTS and chronic pain of the arm/hand who were randomly distributed into two groups to receive topical menthol (Biofreeze) or placebo (gel with a menthol scent) during the working day and 48 hours later the other treatment (crossover design). Participants rated arm/hand pain intensity during...... the last hour of work (scale 0-10) immediately before 1, 2, and 3 hours after application. Furthermore, global rating of change (GROC) in arm/hand pain was assessed 3 hours after application. Compared with placebo, pain intensity and GROC improved more following application of topical menthol (P = 0...

  20. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.

    Science.gov (United States)

    McDougle, C J; Holmes, J P; Carlson, D C; Pelton, G H; Cohen, D J; Price, L H

    1998-07-01

    Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (Pautism (Pautism in adults.

  1. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients.

    Science.gov (United States)

    McKee, P J; Blacklaw, J; Forrest, G; Gillham, R A; Walker, S M; Connelly, D; Brodie, M J

    1994-01-01

    1. The effect of carbamazepine (CBZ), sodium valproate (VPA) and phenytoin (PHT) on the pharmacokinetics of oxcarbazepine (OXC) was explored in three groups of 12 epileptic patients taking one of these drug as monotherapy. 2. Each patient took a single 600 mg dose of OXC followed 7 days later by 3 weeks' treatment with OXC 300 mg thrice daily and matched placebo in random order. 3. Seven untreated patients, acting as controls, were prescribed the single OXC dose and 3 weeks' active treatment only. 4. In those patients completing the study, the area under the concentration-time curve (AUC) at steady-state for hydroxycarbazepine (OHCZ), the active metabolite of OXC, was significantly lower in the CBZ-treated group than in controls (P effects during treatment with OXC compared with one taking placebo (P < 0.01). 8. There were no important changes in cognitive function testing during administration of OXC compared with placebo. 9. Standard doses of OXC can be given as add-on therapy in epileptic patients receiving CBZ, VPA or PHT without producing a clinically relevant pharmacokinetic interaction. PMID:8148215

  2. Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

    Science.gov (United States)

    Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

    2013-08-01

    Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

  3. Effect of BCAA supplement timing on exercise-induced muscle soreness and damage: a pilot placebo-controlled double-blind study.

    Science.gov (United States)

    Ra, Song-Gyu; Miyazaki, Teruo; Kojima, Ryo; Komine, Shoichi; Ishikura, Keisuke; Kawanaka, Kentaro; Honda, Akira; Matsuzaki, Yasushi; Ohmori, Hajime

    2017-09-22

    The aim of present study was to compare the effects of branched-chain amino acid (BCAA) supplementation taken before or after exercise on delayed onset muscle soreness (DOMS) and exercise-induced muscle damage (EIMD). Fifteen young men (aged 21.5 ± 0.4 years) were given either BCAA (9.6 g·day-1) or placebo before and after exercise (and for 3 days prior to and following the exercise day) in three independent groups: the Control group (placebo before and after exercise), the PRE group (BCAA before exercise and placebo after exercise), and the POST group (placebo before exercise and BCAA after exercise). Participants performed 30 repetitions of eccentric exercise with the non-dominant arm. DOMS, upper arm circumference (CIR), elbow range of motion (ROM), serum creatine kinase (CK), lactate dehydrogenase (LDH), and aldolase, BCAA, and Beta-hydroxy-Beta-methylbutyrate (3HMB) were measured immediately before and after the exercise and on the following 4 days. Serum BCAA and 3HMB concentrations increased significantly in the PRE group immediately after the exercise, recovering to baseline over the following days. In the days following the exercise day, DOMS, CIR, and ROM were significantly improved in the PRE group compared to the Control group, with weaker effects in the POST group. Serum activities of CK, LDH, and aldolase in the days following the exercise day were significantly suppressed in the PRE group compared to Control group. Present study confirmed that repeated BCAA supplementation before exercise had a more beneficial effect in attenuating DOMS and EIMD induced by eccentric exercise than repeated supplementation after exercise.

  4. Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study.

    Science.gov (United States)

    Michopoulos, Vasiliki; Norrholm, Seth D; Stevens, Jennifer S; Glover, Ebony M; Rothbaum, Barbara O; Gillespie, Charles F; Schwartz, Ann C; Ressler, Kerry J; Jovanovic, Tanja

    2017-09-01

    Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all pextinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (pextinction and discrimination in individuals with PTSD. Copyright © 2017 Elsevier Ltd. All rights

  5. Oral sumatriptan for migraine in children and adolescents: a randomized, multicenter, placebo-controlled, parallel group study.

    Science.gov (United States)

    Fujita, Mitsue; Sato, Katsuaki; Nishioka, Hiroshi; Sakai, Fumihiko

    2014-04-01

    The objective of this article is to evaluate the efficacy and tolerability of two doses of oral sumatriptan vs placebo in the acute treatment of migraine in children and adolescents. Currently, there is no approved prescription medication in Japan for the treatment of migraine in children and adolescents. This was a multicenter, outpatient, single-attack, double-blind, randomized, placebo-controlled, parallel-group study. Eligible patients were children and adolescents aged 10 to 17 years diagnosed with migraine with or without aura (ICHD-II criteria 1.1 or 1.2) from 17 centers. They were randomized to receive sumatriptan 25 mg, 50 mg or placebo (1:1:2). The primary efficacy endpoint was headache relief by two grades on a five-grade scale at two hours post-dose. A total of 178 patients from 17 centers in Japan were enrolled and randomized to an investigational product in double-blind fashion. Of these, 144 patients self-treated a single migraine attack, and all provided a post-dose efficacy assessment and completed the study. The percentage of patients in the full analysis set (FAS) population who report pain relief at two hours post-treatment for the primary endpoint was higher in the placebo group than in the pooled sumatriptan group (38.6% vs 31.1%, 95% CI: -23.02 to 8.04, P  = 0.345). The percentage of patients in the FAS population who reported pain relief at four hours post-dose was higher in the pooled sumatriptan group (63.5%) than in the placebo group (51.4%) but failed to achieve statistical significance ( P  = 0.142). At four hours post-dose, percentages of patients who were pain free or had complete relief of photophobia or phonophobia were numerically higher in the sumatriptan pooled group compared to placebo. Both doses of oral sumatriptan were well tolerated. No adverse events (AEs) were serious or led to study withdrawal. The most common AEs were somnolence in 6% (two patients) in the sumatriptan 25 mg treatment group and chest

  6. An Extract of Glycyrrhiza glabra (GutGard Alleviates Symptoms of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Kadur Ramamurthy Raveendra

    2012-01-01

    Full Text Available A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of GutGard, an extract of Glycyrrhiza glabra, in patients with functional dyspepsia. The primary outcome variables of the study were the change in the severity symptoms and the global assessment of efficacy. The quality of life was evaluated as a secondary outcome measure. The patients received either placebo or GutGard (75 mg twice daily for 30 days. Efficacy was evaluated in terms of change in the severity of symptoms (as measured by 7-point Likert scale, the global assessment of efficacy, and the assessment of quality of life using the short-form Nepean Dyspepsia Index. In comparison with placebo, GutGard showed a significant decrease (P≤.05 in total symptom scores on day 15 and day 30, respectively. Similarly, GutGard showed marked improvement in the global assessment of efficacy in comparison to the placebo. The GutGard group also showed a significant decrease (P≤.05 in the Nepean dyspepsia index on day 15 and 30, respectively, when compared to placebo. GutGard was generally found to be safe and well-tolerated by all patients. GutGard has shown significant efficacy in the management of functional dyspepsia.

  7. Protective effects of fermented honeybush (Cyclopia intermedia) extract (HU-018) against skin aging: a randomized, double-blinded, placebo-controlled study.

    Science.gov (United States)

    Choi, Sun Young; Hong, Ji Yeon; Ko, Eun Jung; Kim, Beom Joon; Hong, Sung-Woon; Lim, Mi Hyoung; Yeon, Sung Hum; Son, Rak Ho

    2018-02-01

    Oxidative stress and photodamage resulting from ultraviolet radiation exposure play key roles in skin aging. Fermented Cyclopia intermedia, which is used to brew honeybush tea, exerts antioxidant and anti-wrinkle effects by inhibiting reactive oxygen species production and downregulating matrix metalloproteinase activity. This randomized, double-blinded, placebo-controlled study aimed to evaluate the efficacy and safety of fermented honeybush (Cyclopia intermedia) extract (HU-018) for skin rejuvenation. 120 Korean subjects with crow's feet wrinkles were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo (negative control, only dextran) for 12 weeks. Wrinkles were evaluated using JANUS ® and PRIMO pico ® . Skin elasticity, hydration and transepidermal water loss were measured. Global skin wrinkle grade was significantly improved in both low-dose and high-dose groups compared to placebo group, as well as for skin hydration and elasticity. Both the low- and high-dose groups showed significantly decreased TEWL compared to the placebo group. There were no adverse effects during the entire study period. Our data indicate that HU-018 is effective for improving skin wrinkles, elasticity, and hydration. Therefore, daily supplementation with fermented honeybush could be helpful for protecting against skin aging.

  8. Randomized, double-blind, placebo-controlled study of Malarone for malaria prophylaxis in non-immune Colombian soldiers.

    Science.gov (United States)

    Soto, Jaime; Toledo, Julia; Luzz, Magda; Gutierrez, Patricia; Berman, Jonathan; Duparc, Stephane

    2006-09-01

    Malarone was compared with placebo in a double-blind, randomized, placebo-controlled trial of prophylaxis of malaria in predominately Plasmodium vivax areas of Colombia. The study population consisted of 180 completely non-immune Colombian soldiers, male, average age 19 years, and average weight 63 kg. Twenty-four subjects were considered unevaluable because of compliance issues, including one Malarone subject (with no detectable drug levels) who became infected with P. vivax. Of the 97 evaluable subjects who received Malarone (250 mg atovaquone plus 100 mg proguanil hydrochloride) daily from 1 day before entering the endemic area to 7 days after leaving the endemic area, none became parasitemic. Of the 46 evaluable placebo subjects, 11 became infected with P. vivax and 2 became infected with Plasmodium falciparum. The protective efficacy of Malarone for all malaria and for P. vivax malaria was 100% (LL 95% CI = 63%) and 100% (LL 95% CI = 58%), respectively, and was 96% if the one case with undetectable blood levels was included. Malarone has high protective efficacy for P. vivax in Colombia.

  9. New validated recipes for double-blind placebo-controlled low-dose food challenges.

    Science.gov (United States)

    Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

    2013-05-01

    Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. Placebo-induced somatic sensations: a multi-modal study of three different placebo interventions.

    Directory of Open Access Journals (Sweden)

    Florian Beissner

    Full Text Available Somatic sensations induced by placebos are a frequent phenomenon whose etiology and clinical relevance remains unknown. In this study, we have evaluated the quantitative, qualitative, spatial, and temporal characteristics of placebo-induced somatic sensations in response to three different placebo interventions: (1 placebo irritant solution, (2 placebo laser stimulation, and (3 imagined laser stimulation. The quality and intensity of evoked sensations were assessed using the McGill pain questionnaire and visual analogue scales (VAS, while subjects' sensation drawings processed by a geographic information system (GIS were used to measure their spatial characteristics. We found that all three interventions are capable of producing robust sensations most frequently described as "tingling" and "warm" that can reach consider-able spatial extent (≤ 205 mm² and intensity (≤ 80/100 VAS. Sensations from placebo stimulation were often referred to areas remote from the stimulation site and exhibit considerable similarity with referred pain. Interestingly, there was considerable similarity of qualitative features as well as spatial patterns across subjects and placebos. However, placebo laser stimulation elicited significantly stronger and more widespread sensations than placebo irritant solution. Finally, novelty seeking, a character trait assessed by the Temperament and Character Inventory and associated with basal dopaminergic activity, was less pronounced in subjects susceptible to report placebo-induced sensations. Our study has shown that placebo-induced sensations are frequent and can reach considerable intensity and extent. As multiple somatosensory subsystems are involved despite the lack of peripheral stimulus, we propose a central etiology for this phenomenon.

  11. Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bone Kerry M

    2009-06-01

    Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

  12. A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood.

    Science.gov (United States)

    Dodd, F L; Kennedy, D O; Riby, L M; Haskell-Ramsay, C F

    2015-07-01

    Evidence suggests interactive effects of the tea components caffeine and L-theanine on behaviour, yet no data exists exploring the impact of the two on cerebral blood flow (CBF). The current placebo-controlled, double-blind, counterbalanced, crossover study examined the effects of caffeine and L-theanine on CBF and extended previous cognitive and mood findings by using lower doses than previous studies of a similar methodology, which more closely reflect the ratios present in tea. Twelve habitual consumers and 12 non-habitual consumers of caffeine each received 75 mg caffeine, 50 mg L-theanine, 75 mg caffeine plus 50 mg L-theanine, and placebo in a counterbalanced order across four separate visits. CBF was measured via near-infrared spectroscopy with cognition and mood assessed at baseline and 30 min post-dose. Salivary caffeine and peripheral haemodynamics were co-monitored. Caffeine reduced oxygenated haemoglobin (oxy-Hb), increased deoxygenated haemoglobin (deoxy-Hb), improved performance on attention tasks and increased overall mood ratings. Increases in deoxy-Hb following caffeine were more pronounced in non-consumers. Some evidence for increased deoxy-Hb remained when caffeine was combined with L-theanine, but this effect was attenuated and the effects of caffeine on oxy-Hb, cognition and mood were eradicated. Combining L-theanine with caffeine, at levels and ratios equivalent to one to two cups of tea, eliminated the vasoconstrictive effect and behavioural effects of caffeine. This supports previous findings of an interaction between these substances, despite a lack of effects of L-theanine in isolation. However, at the levels tested here, this did not lead to a positive impact on behaviour.

  13. A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease

    DEFF Research Database (Denmark)

    Hjermind, Lena Elisabeth

    2013-01-01

    BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepir......BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect...... of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington...... between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with latrepirdine for 6 months was safe and well tolerated but did not improve cognition or global function relative to placebo. TRIAL...

  14. A double-blind randomized placebo-controlled feasibility study evaluating individualized homeopathy in managing pain of knee osteoarthritis.

    Science.gov (United States)

    Koley, Munmun; Saha, Subhranil; Ghosh, Shubhamoy

    2015-07-01

    Few homeopathic complexes seemed to produce significant effects in osteoarthritis; still, individualized homeopathy remained untested. We evaluated the feasibility of conducting an efficacy trial of individualized homeopathy in osteoarthritis. A prospective, parallel-arm, double-blind, randomized, placebo-controlled pilot study was conducted from January to October 2014 involving 60 patients (homeopathy, n = 30; placebo, n = 30) who were suffering from acute painful episodes of knee osteoarthritis and visiting the outpatient clinic of Mahesh Bhattacharyya Homeopathic Medical College and Hospital, West Bengal, India. Statistically significant reduction was achieved in 3 visual analog scales (measuring pain, stiffness, and loss of function) and Osteoarthritis Research Society International scores in both groups over 2 weeks (P .05). Overall, homeopathy did not appear to be superior to placebo; still, further rigorous evaluation in this design involving a larger sample size seems feasible in future. Clinical Trials Registry, India (CTRI/2014/05/004589). © The Author(s) 2015.

  15. A double-blind, randomized, placebo-controlled, fixed-dose phase III study of vilazodone in patients with generalized anxiety disorder.

    Science.gov (United States)

    Gommoll, Carl; Durgam, Suresh; Mathews, Maju; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Thase, Michael E

    2015-06-01

    Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 ClinicalTrials.gov) evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (-1.80 [-3.26, -0.34]; P = .0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P = .0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  16. Trial of early noninvasive ventilation for ALS: A pilot placebo-controlled study.

    Science.gov (United States)

    Jacobs, Teresa L; Brown, Devin L; Baek, Jonggyu; Migda, Erin M; Funckes, Timothy; Gruis, Kirsten L

    2016-11-01

    To evaluate the use and tolerability of noninvasive positive pressure ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS) early in their disease by comparing active NIV and sham NIV in patients not yet eligible for NIV use as recommended by practice guidelines. This was a single-center, prospective, double-blind, randomized, placebo (sham)-controlled pilot trial. Patients with ALS were randomized to receive either sham NIV or active NIV and underwent active surveillance approximately every 3 months until they reached a forced vital capacity (FVC) NIV for clinical symptom management. In total, 54 participants were randomized. The mean NIV use was 2.0 hours (95% confidence interval [CI] 1.1-3.0) per day in the sham NIV treatment group and 3.3 hours (CI 2.0-4.6) per day in the active NIV group, which did not differ by treatment group (p = 0.347). The majority of sham NIV participants (88%) and active NIV participants (73%) reported only mild or no problem with NIV use. Difference of change in FVC through the treatment period by group (0.44 per month) favored active NIV (p = 0.049). Survival and changes in maximal inspiratory or expiratory pressure did not differ between treatment groups. The efficacy of early NIV in ALS should be tested in randomized, placebo-controlled trials. The trial is registered on clinicaltrials.gov (NCT00580593). This study provides Class II evidence that for patients with ALS, adherence with NIV and sham NIV are similar. © 2016 American Academy of Neurology.

  17. Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

    Directory of Open Access Journals (Sweden)

    M.E. Bigal

    2002-10-01

    Full Text Available Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05 of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50% and use of rescue medication (dipyrone = 20%, placebo = 47.6% for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

  18. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

    OpenAIRE

    Chetna Deep Lamba; Praveen Oberai; Raj K Manchanda; Padmalaya Rath; P Hima Bindu; Maya Padmanabhan

    2018-01-01

    Background and Objectives: This study was conducted with the primary objective of evaluating efficacy of Homoeopathy in establishing the menstrual regularity with improvement in either ultrasonological findings or hirsutism/acne. The quality of life was also assessed using polycystic ovary syndrome questionnaire (PCOSQ). Materials and Methods: A single-blind, randomised, placebo-controlled pilot study was conducted from February 2014 to May 2015 at two research centres. The cases fulfilling t...

  19. Noncultured keratinocyte/melanocyte cosuspension: effect on reepithelialization and repigmentation--a randomized, placebo-controlled study.

    Science.gov (United States)

    Back, Christopher; Dearman, Bronwyn; Li, Amy; Neild, Tim; Greenwood, John E

    2009-01-01

    Randomized controlled trials in the literature investigating the efficacy of noncultured keratinocyte/melanocyte suspensions are scarce; however, the advocates of such techniques press the value of their application based largely on case studies and anecdote. Caucasian patients with burn hypopigmentation seldom request cosmetic revision making worthwhile clinical trials difficult so that informal case treatments with new therapies generate anecdotal results. A randomized, placebo-controlled trial was carried out to evaluate whether cosuspensions of noncultured skin cells are capable of (1) decreasing the time to reepithelialization and (2) reestablishing pigmentation in vitiligo leukoderma following epidermal/superficial dermal ablation (in the knowledge that a positive result would make the technique likely to be successful in burn hypopigmentation). Vitiligo is common and is socially more debilitating such that suitable trial subjects for new therapies from this pool are more forthcoming. This study demonstrated that suspensions of noncultured keratinocytes and melanocytes do not decrease the time to epithelialization of superficial partial thickness wounds compared with controls. It also suggested that the achievement, quality, and duration of any pigmentation were unpredictable and largely disappointing. Some pigmentation was recorded in placebo-treated areas indicating an effect of the method of epidermal ablation in these patients. These findings have mandated a complete review of the use of these techniques in burn care at the Royal Adelaide Hospital; they have been omitted from surgical protocols where the aim of use was to speed reepithelialization. Their infrequent use in burns hypopigmentation will continue contingent on the successful repigmentation of a test patch.

  20. Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study123

    Science.gov (United States)

    Velmurugan, Shanti; Gan, Jasmine Ming; Rathod, Krishnaraj S; Khambata, Rayomand S; Ghosh, Suborno M; Hartley, Amy; Van Eijl, Sven; Sagi-Kiss, Virag; Chowdhury, Tahseen A; Curtis, Mike; Kuhnle, Gunter GC; Wade, William G; Ahluwalia, Amrita

    2016-01-01

    Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a

  1. A placebo-controlled investigation of synaesthesia-like experiences under LSD.

    Science.gov (United States)

    Terhune, Devin B; Luke, David P; Kaelen, Mendel; Bolstridge, Mark; Feilding, Amanda; Nutt, David; Carhart-Harris, Robin; Ward, Jamie

    2016-07-29

    The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. [The concept of placebo and the effect of placebo].

    Science.gov (United States)

    Göka, Erol

    2002-01-01

    The discussions about what placebo means and how its effect occurs go far back in the history of medicine. In general medicinal understanding, placebo means the subjective feeling of a positive effect in response to something that is used for curative intentions. In spite of difficulties in its definition and unknown content, its existence is generally accepted. What is discussed is its level of effectiveness in any disorder and medication. The placebo effect varies not only among diseases but also among regions and countries. Even the physicians' belief in a placebo increases its effect. Another interesting point about the placebo is its side effects. In many placebo controlled studies, the side effects of the placebo are found to be greater than those of real drugs. Different from other diseases, psychiatric disorders have strong connections with the placebo effect. The results of many studies support this idea. The increasing importance of placebos in psychiatry is really an interesting subject. For some people, the reason for this is hidden in the nature of psychiatric diseases. However, nonpharmacologic placebos such as "inspiration", "convincing", "confidence", and "belief" are believed to play a central role in psychiatry. In this article, placebo (the placebo effect) is defined, the implications of placebo in general medicine or psychiatry are discussed, and specific or nonspecific treatment methods are explained. The effects of a placebo on both the patient and the physician are emphasized. The significance of the placebo effect in psychiatry is also mentioned; and a new point of view, based upon the importance of symbolization and satisfaction is introduced in treatment and related action mechanisms.

  3. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

    DEFF Research Database (Denmark)

    Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

    2010-01-01

    This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

  4. Eustress and Malondialdehyde (MDA: Role of Panax Ginseng: Randomized, placebo controlled prospective study

    Directory of Open Access Journals (Sweden)

    hayder Al-kuraishy

    2017-06-01

    Full Text Available Objective: The aim of present study was evaluation the effect of Panax Ginseng on malondialdehyde (MDA serum levels during eustress on normal healthy volunteers. Method: 65 healthy volunteers were recruited from medical students at college of medicine with age range (22.61±3.63 years, the volunteers were divided into two groups, Group A: 35 subjects treated by Panax Ginseng 500mg/day regarded as treated group. Group B: 30 subjects treated by placebo 500mg/day regarded as control group. Baseline data was obtained and then after one month of study for following induction of psychological stress through daily psychomotor performance task and visual working memory accuracy testing while; stress-induced oxidative stress was assessed by malondialdehyde (MDA serum levels. Results: placebo showed significant increases in MDA serum levels p=0.0004 which related with significant increases in perceived stress scale from p<0.0001, while; Panax Ginseng led to significant reduction in MDA serum levels from p<0.01 that related with significant increment in perceived stress scale p=0.02. Conclusion: An MDA serum level is positively correlated with eustress and this association is modulated by   Panax Ginseng therapy that produced significant reduction in MDA and rising of eustress level.

  5. Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized, placebo controlled, cross-over study

    Directory of Open Access Journals (Sweden)

    Fisher-Wellman Kelsey H

    2009-08-01

    Full Text Available Abstract Background We have recently reported that the dietary supplement Meltdown® increases plasma norepinephrine (NE, epinephrine (EPI, glycerol, free fatty acids (FFA, and metabolic rate in men. However, in that investigation measurements ceased at 90 minutes post ingestion, with values for blood borne variables peaking at this time. It was the purpose of the present investigation to extend the time course of measurement to 6 hours, and to include women within the design to determine if sex differences to treatment exist. Methods Ten men (24 ± 4 yrs and 10 women (22 ± 2 yrs ingested Meltdown® or a placebo, using a randomized, cross-over design with one week separating conditions. Blood samples were collected immediately before supplementation and at one hour intervals through 6 hours post ingestion. A standard meal was provided after the hour 3 collection. Samples were assayed for EPI, NE, glycerol, and FFA. Five minute breath samples were collected at each time for measurement of metabolic rate and substrate utilization. Area under the curve (AUC was calculated. Heart rate and blood pressure were recorded at all times. Data were also analyzed using a 2 (sex × 2 (condition × 7 (time repeated measures analysis of variance, with Tukey post hoc testing. Results No sex × condition interactions were noted for AUC for any variable (p > 0.05. Hence, AUC data are collapsed across men and women. AUC was greater for Meltdown® compared to placebo for EPI (367 ± 58 pg·mL-1·6 hr-1 vs. 183 ± 27 pg·mL-1·6 hr-1; p = 0.01, NE (2345 ± 205 pg·mL-1·6 hr-1 vs. 1659 ± 184 pg·mL-1·6 hr-1; p = 0.02, glycerol (79 ± 8 μg·mL-1·6 hr-1 vs. 59 ± 6 μg·mL-1·6 hr-1; p = 0.03, FFA (2.46 ± 0.64 mmol·L-1·6 hr-1 vs. 1.57 ± 0.42 mmol·L-1·6 hr-1; p = 0.05, and kilocalorie expenditure (439 ± 26 kcal·6 hrs-1 vs. 380 ± 14 kcal·6 hrs-1; p = 0.02. No effect was noted for substrate utilization (p = 0.39. Both systolic and diastolic blood pressure

  6. Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol® on glycemic control of subjects with impaired fasting glucose

    Directory of Open Access Journals (Sweden)

    Evans M

    2015-06-01

    Full Text Available Malkanthi Evans,1 William V Judy,2 Dale Wilson,3 John A Rumberger,4 Najla Guthrie,1 1KGK Synergize Inc., London, ON, Canada; 2SIBR Research Inc., Bradenton, FL, USA; 3London Health Sciences Center, University of Western Ontario, London, ON, Canada; 4Princeton Longevity Center, Princeton, NJ, USA Background: This study investigated the efficacy of Diabetinol® in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. Subjects and methods: Fifty subjects, aged 18–75 years, with fasting blood glucose ≤15.4 mmol/L, hemoglobin A1c levels ≤12%, and a body mass index between 25 and 40 kg/m2, were enrolled in a 24-week, randomized, double-blind, placebo-controlled, parallel study. Diabetinol® or placebo was administered as 2×525 mg capsules/day. Results: In the Diabetinol® group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax of serum glucose or area under the curve (AUC0–240 minutes. The time to Cmax was longer for participants on Diabetinol® than placebo group at week 12 (P=0.01. Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol® group versus placebo. The Diabetinol® group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09 and 3.2 mg/dL at week 24 (P=0.41 over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol® group

  7. Randomized placebo control study of metformin in psoriasis patients with metabolic syndrome (systemic treatment cohort

    Directory of Open Access Journals (Sweden)

    Surjit Singh

    2017-01-01

    Full Text Available Background: Psoriasis has been found to be associated with obesity, metabolic syndrome (MS, diabetes, and cardiovascular risk factors. Metformin treatment showed improvement in cardiovascular risk factors and hyperinsulinemia. Objective: To evaluate the efficacy and safety of metformin in psoriasis patients with MS. Materials and Methods: This was a single-center, parallel-group, randomized, open-label study with blinded end point assessment of metformin (1000 mg once daily for 12 weeks; n = 20 and placebo (n = 18 in psoriasis patients with MS. Total sample size was 38 participants. Results: Statistically significant improvement was observed in mean percentage change in erythema, scaling, and induration (ESI (P = 0.048 in metformin as compared to placebo while mean percentage change in psoriasis area and severity index (PASI and physician global assessment (PGA scores was not significant (PASI - P = 0.215, PGA - P = 0.070. There was a statistically significant difference in percentage of parameters of MS improved following 12 weeks of treatment in metformin (19% as compared to placebo (8.9% group (P = 0.046. Statistically significant difference in percentage of patients achieving 75% reduction in ESI scores (P = 0.024. Significant improvement was observed in mean weight, body mass index (BMI, total cholesterol, and low-density lipoprotein (LDL cholesterol in metformin group as compared to placebo. Improvement in BMI, fasting plasma glucose, serum triglycerides, high-density lipoprotein, LDL, systolic blood pressure, diastolic blood pressure, and total cholesterol was statistically significant in metformin group over the period of 12 weeks. There was no significant difference in adverse events in two groups except weight gain. Conclusion: Metformin has shown improvement in psoriasis and parameters of MS, hence can be used for the benefit of psoriasis patients having MS. Large, controlled studies are needed to confirm.

  8. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

  9. Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men

    Science.gov (United States)

    Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-co...

  10. Acute neuropharmacological effects of atomoxetine on inhibitory control in ADHD children: A fNIRS study

    Directory of Open Access Journals (Sweden)

    Masako Nagashima

    2014-01-01

    Full Text Available The object of the current study is to explore the neural substrate for effects of atomoxetine (ATX on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD using functional near-infrared spectroscopy (fNIRS. We monitored the oxy-hemoglobin signal changes of sixteen ADHD children (6–14 years old performing a go/no-go task before and 1.5 h after ATX or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Sixteen age- and gender-matched normal controls without ATX administration were also monitored. In the control subjects, the go/no-go task recruited the right inferior and middle prefrontal gyri (IFG/MFG, and this activation was absent in pre-medicated ADHD children. The reduction of right IFG/MFG activation was acutely normalized after ATX administration but not placebo administration in ADHD children. These results are reminiscent of the neuropharmacological effects of methylphenidate to up-regulate reduced right IFG/MFG function in ADHD children during inhibitory tasks. As with methylphenidate, activation in the IFG/MFG could serve as an objective neuro-functional biomarker to indicate the effects of ATX on inhibitory control in ADHD children. This promising technique will enhance early clinical diagnosis and treatment of ADHD in children, especially in those with a hyperactivity/impulsivity phenotype.

  11. The challenge of recruiting patients into a placebo-controlled surgical trial

    DEFF Research Database (Denmark)

    Hare, Kristoffer B; Lohmander, L Stefan; Roos, Ewa M.

    2014-01-01

    BACKGROUND: Randomized placebo-controlled trials represent the gold standard in evaluating healthcare interventions but are rarely performed within orthopedics. Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo...

  12. The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Poulsen, L K; Jacobi, H H

    2002-01-01

    BACKGROUND: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North Americ...

  13. Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Sánchez-de la Osa Reinaldo B

    2008-02-01

    Full Text Available Abstract Background High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC. Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. Results Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%. At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before, with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated

  14. Effects of Pomegranate Juice on Cardiovascular Risk Factors in Patients with Metabolic Syndrome: a Double-Blinded, Randomized Crossover Controlled Trial.

    Science.gov (United States)

    Moazzen, Hossein; Alizadeh, Mohammad

    2017-06-01

    The aim of this study is to investigate the simultaneous effect of pomegranate juice on components of the metabolic syndrome, including high sensitive C-reactive protein (hs-CRP) as an inflammatory index and glycemic and lipid profile indices in patients with metabolic syndrome. In a double- blind 2*2 crossover study, 30 individuals suffering from metabolic syndrome received a daily dose of 500 mL pomegranate juice for a period of one week. After one week of wash out period, they received a placebo for one week. Lipid profile, blood glucose control indices including fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), systolic and diastolic blood pressure, and hs-CRP were measured at the beginning and end of the study. To analyze the data, a repeated measure analysis of variance and a t-test were performed. The results indicated that in comparison to the placebo, pomegranate juice was more effective in reducing the systolic and diastolic blood pressure (p = 0.00) and hs-CRP (p = 0.018). The level of triglyceride (p = 0.030) and very low-density lipoproteins cholesterol (VLDL-C) (p = 0.014) were increased after the consumption of pomegranate juice, as opposed to the baseline condition. The rest of lipid profile, fasting blood glucose (FBS), insulin, and HOMA-IR of the participants did not show any significant difference. Natural pomegranate juice supplementation lowered the level of systolic and diastolic blood pressure in patients with metabolic syndrome as well as their blood hs-CRP. However, it also increased their triglyceride and VLDL-C.

  15. Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

    Science.gov (United States)

    Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

    2016-06-01

    Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

  16. A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain.

    Science.gov (United States)

    McElroy, Susan L; Winstanley, Erin; Mori, Nicole; Martens, Brian; McCoy, Jessica; Moeller, Dianna; Guerdjikova, Anna I; Keck, Paul E

    2012-04-01

    Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

  17. Multicenter, randomized, placebo-controlled study of the nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene in distributive shock.

    Science.gov (United States)

    Kinasewitz, Gary T; Privalle, Christopher T; Imm, Amy; Steingrub, Jay S; Malcynski, John T; Balk, Robert A; DeAngelo, Joseph

    2008-07-01

    To assess the safety and efficacy of the hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene (PHP), in patients with distributive shock. Phase II multicenter, randomized (1:1), placebo-controlled study. Fifteen intensive care units in North America. Sixty-two patients with distributive shock, > or = 2 systemic inflammatory response syndrome criteria, and persistent catecholamine dependence despite adequate fluid resuscitation (pulmonary capillary wedge pressure > or = 12). Patients were randomized to PHP at 0.25 mL/kg/hr (20 mg/kg/hr), or an equal volume of placebo, infused for up to 100 hrs, in addition to conventional vasopressor therapy. Because treatment could not be blinded, vasopressors and ventilatory support were weaned by protocol. Sixty-two patients were randomized to PHP (n = 33) or placebo (n = 29). Age, sex, etiology of shock (sepsis in 94%), and Acute Physiology and Chronic Health Evaluation II scores (33.1 +/- 8.3 vs. 30 +/- 7) were similar in PHP and placebo patients, respectively. Baseline plasma nitrite and nitrate levels were markedly elevated in both groups. PHP infusion increased systemic blood pressure within minutes. Overall 28-day mortality was similar (58% PHP vs. 59% placebo), but PHP survivors were weaned off vasopressors faster (13.7 +/- 8.2 vs. 26.3 +/- 21.4 hrs; p = .07) and spent less time on mechanical ventilation (10.4 +/- 10.2 vs. 17.4 +/- 9.9 days; p = .21). The risk ratio (PHP/placebo) for mortality was .79 (95% confidence interval, .39-1.59) when adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II score, and etiology of sepsis. No excess medical interventions were noted with PHP use. PHP survivors left the intensive care unit earlier (13.6 +/- 8.6 vs. 17.9 +/- 8.2 days; p = .21) and more were discharged by day 28 (57.1 vs. 41.7%). PHP is a hemodynamically active nitric oxide scavenger. The role of PHP in distributive shock remains to be determined.

  18. Low to moderate alcohol consumption on serum vitamin D and other indicators of bone health in postmenopausal women in a controlled feeding study

    Science.gov (United States)

    Heavy alcohol drinking adversely affects vitamin D status and bone health. However, data from randomized, placebo-controlled trials (RCTs) on the effects of low to moderate alcohol consumption on vitamin D status and bone health in humans is unavailable. The objective of this cross-over RCT was to e...

  19. Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study

    NARCIS (Netherlands)

    Sakkers, Ralph; Kok, Dieke; Engelbert, Raoul; van Dongen, Alice; Jansen, Maarten; Pruijs, Hans; Verbout, Ab; Schweitzer, Dave; Uiterwaal, Cuno

    2004-01-01

    Non-randomised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta. We assessed the effects of oral olpadronate in children with this disorder in a randomised double-blind placebo-controlled trial. 34 children recruited from the Dutch national centre for

  20. No effect of Pindolol on postural hypotension in type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. A randomised double-blind controlled study

    DEFF Research Database (Denmark)

    Dejgård, A; Hilsted, J

    1988-01-01

    of this therapy we performed a double-blind placebo controlled cross-over study with Pindolol (15 mg/day). Eight Type 1 (insulin-dependent) diabetic patients with autonomic neuropathy and signs and symptoms of orthostatic hypotension (systolic blood pressure decrease greater than 30 mm Hg when standing......) participated in the study. Patients were treated for 10 weeks. Clinical examinations were performed every fortnight and patients registered postural symptoms twice daily on a visual analog scale. No significant changes were seen in blood pressure recordings, heart-rate or visual analog scale registration...... during treatment with Pindolol compared to placebo. Our study does not support the suggestion that Pindolol is a valuable drug for treatment of diabetic patients with autonomic neuropathy and postural giddiness....

  1. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Kim, Suck Won

    2009-07-01

    Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss. Data on the pharmacologic treatment of trichotillomania are limited to conflicting studies of serotonergic medications. N-acetylcysteine, an amino acid, seems to restore the extracellular glutamate concentration in the nucleus accumbens and, therefore, offers promise in the reduction of compulsive behavior. To determine the efficacy and tolerability of N-acetylcysteine in adults with trichotillomania. Twelve-week, double-blind, placebo-controlled trial. Ambulatory care center. Fifty individuals with trichotillomania (45 women and 5 men; mean [SD] age, 34.3 [12.1] years). N-acetylcysteine (dosing range, 1200-2400 mg/d) or placebo was administered for 12 weeks. Patients were assessed using the Massachusetts General Hospital Hair Pulling Scale, the Clinical Global Impression scale, the Psychiatric Institute Trichotillomania Scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using analysis of variance modeling analyses and linear regression in an intention-to-treat population. Patients assigned to receive N-acetylcysteine had significantly greater reductions in hair-pulling symptoms as measured using the Massachusetts General Hospital Hair Pulling Scale (P acetylcysteine use compared with 16% taking placebo (P = .003). Significant improvement was initially noted after 9 weeks of treatment. This study, the first to our knowledge that examines the efficacy of a glutamatergic agent in the treatment of trichotillomania, found that N-acetylcysteine demonstrated statistically significant reductions in trichotillomania symptoms. No adverse events occurred in the N-acetylcysteine group, and N-acetylcysteine was well tolerated. Pharmacologic modulation of the glutamate system may prove to be useful in the control of a range of compulsive behaviors. clinicaltrials.gov Identifier: NCT00354770.

  2. Efficacy and safety of two fast-absorbing formulations of paracetamol in combination with caffeine for episodic tension-type headache: results from two randomized placebo- and active-controlled trials

    Directory of Open Access Journals (Sweden)

    Yue Y

    2017-06-01

    Full Text Available Yong Yue,1 Kenneth D Reed,1 Lucy Shneyer,2 Dongzhou J Liu3 1GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, 2Shneyer Statistics LLC, Denville, NJ, 3GlaxoSmithKline, Collegeville, PA, USA Objectives: Two randomized placebo-controlled trials evaluated whether combining rapid-acting paracetamol formulations with caffeine resulted in faster/greater relief of episodic tension-type headache (ETTH compared with placebo and over-the-counter (OTC analgesics. Both studies were prematurely terminated. Materials and methods: In the single-blind crossover study 1, adults with ETTH (n=66 received three of the following in random sequence: paracetamol 1,000 mg with sodium bicarbonate 650 mg and caffeine 130 mg; paracetamol 1,000 mg; ibuprofen 400 mg; and placebo. In the double-blind parallel-group study 2, adults with ETTH (n=157 were randomly assigned 2:2:1 to treat up to three headaches with paracetamol with Optizorb technology 1,000 mg plus caffeine 130 mg; ibuprofen 400 mg; and placebo. Results: In study 1, the primary outcome – mean time to perceptible pain relief – was 36.7, 38, 48.9, and 42.7 minutes in the paracetamol–sodium bicarbonate–caffeine, ibuprofen, paracetamol, and placebo groups, respectively; differences were not statistically significant. In study 2, the weighted sum of pain intensity (scale of 0 [no pain] to 4 [severe pain] difference from the time of treatment to hour 4, the primary outcome, showed numerically favorable differences for paracetamol with Optizorb–caffeine compared with ibuprofen (difference in least square means −0.3, 95% confidence interval −1.05 to 0.45 and placebo (−0.47, 95% confidence interval −1.36 to 0.42. In both studies, secondary outcomes suggested faster and greater relief with rapid paracetamol–caffeine compared with placebo and paracetamol; a few of these outcomes achieved statistical significance at ~45–90 minutes in study 1. Adverse events were mostly mild and consistent with known

  3. Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

    NARCIS (Netherlands)

    de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

    Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

  4. Therapeutic Benefit of Smoked Cannabis in Randomized Placebo-Controlled Studies.

    Science.gov (United States)

    Bowen, Lynneice L; McRae-Clark, Aimee L

    2018-01-01

    The medicinal use of marijuana has been legalized in 28 states, with a wide range of specificity for approved medical conditions. Even with the emergence of non-combustion-based delivery systems, 90% of marijuana users in 2014 used smoked marijuana. This review summarizes the data available on the use of smoked marijuana for medical purposes. A literature search was performed to retrieve randomized controlled trials exploring the efficacy of smoked cannabis for treatment of a medical condition. Studies with the primary end point listed as the effect of smoked cannabis on a disease-specific characteristic were included. Open-label studies and studies using other administration methods were excluded. Seven studies met these criteria and were included in this review. Cannabis did not outperform placebo on experimentally evoked pain or the timed walk test. Clear evidence indicates that smoked cannabis reduces intraocular pressure, but the effect is too brief (less than 4 hrs) to be of therapeutic benefit for this chronic disorder. Consistent evidence also showed that smoked marijuana, even at lower concentrations of tetrahydrocannabinol, increased total daily calorie intake and number of eating occasions. Neither of the studies with quality of life as secondary outcome measures revealed statistically significantly improved outcomes with cannabis use. © 2017 Pharmacotherapy Publications, Inc.

  5. Botulinum Toxin in Parkinson Disease Tremor: A Randomized, Double-Blind, Placebo-Controlled Study With a Customized Injection Approach.

    Science.gov (United States)

    Mittal, Shivam Om; Machado, Duarte; Richardson, Diana; Dubey, Divyanshu; Jabbari, Bahman

    2017-09-01

    In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor, but many patients (30%-70%) develop moderate to severe hand weakness, limiting the use of onabotulinumtoxinA in clinical practice. To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for the treatment of tremor in PD. In this double-blind, placebo-controlled, crossover trial, 30 patients each received 7 to 12 (mean, 9) IncoA injections into hand and forearm muscles using a customized approach. The study was performed from June 1, 2012, through June 30, 2015, and participants were followed for 24 weeks. Treatment efficacy was evaluated by the tremor subsets of the Unified Parkinson's Disease Rating Scale and the Patient Global Impression of Change 4 and 8 weeks after each of the 2 sets of treatments. Hand strength was assessed using an ergometer. There was a statistically significant improvement in clinical rating scores of rest tremor and tremor severity 4 and 8 weeks after the IncoA injection and of action/postural tremor at 8 weeks. There was a significant improvement in patient perception of improvement at 4 and 8 weeks in the IncoA group. There was no statistically significant difference in grip strength at 4 weeks between the 2 groups. Injection of IncoA via a customized approach improved PD tremor on a clinical scale and patient perception, with a low occurrence of significant hand weakness. clinicaltrials.gov Identifier: NCT02419313. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  6. A randomized, placebo-controlled pilot study of patients with spontaneous intraventricular haemorrhage treated with intraventricular thrombolysis.

    Science.gov (United States)

    King, Nicolas K K; Lai, Jin Li; Tan, Li Bing; Lee, Kah Keow; Pang, Boon Chuan; Ng, Ivan; Wang, Ernest

    2012-07-01

    Intraventricular hemorrhage (IVH) occurring after spontaneous intracerebral hemorrhage (ICH) is an independent risk factor for mortality. The use of intraventricular urokinase (Uk) to reduce intraventricular blood clot volume and improve outcome was investigated. Patients with IVH requiring external ventricular drainage were recruited and randomized into a double-blind placebo controlled study. Assessments of collected cerebrospinal fluid (CSF) haemoglobin (Hb) and serial CT scans were performed. The study outcomes were: infection rates, length of stay in the intensive care unit, survival, National Institutes of Health Stroke Scale score; and modified Rankin Scale scores. Our results showed an increase in both the drained CSF Hb concentration in patients treated with Uk compared to placebo and in the rate of resolution clot volume. No differences were found in the other outcome measures but there was a trend towards lowered mortality in the group treated with Uk. Therefore, intraventricular Uk resulted in faster resolution of IVH with no adverse events. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study

    DEFF Research Database (Denmark)

    Stein, Dan J; Andersen, Elisabeth Anne Wreford; Tonnoir, Brigitte

    2007-01-01

    OBJECTIVE: A randomized, placebo controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive-compulsive disorder (OCD), using paroxetine as the active reference. RESEARCH DESIGN AND METHODS: A total of 466 adults with OCD from specialized...... clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10 mg/day (n = 116), escitalopram 20 mg/day (n = 116), paroxetine 40 mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy...... of adverse events, and on changes in vital signs (blood pressure and pulse). Main outcome measures; RESULTS: Escitalopram 20 mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10 mg/day and paroxetine 40 mg/day were also effective...

  8. A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico.

    Science.gov (United States)

    Rossignol, J F; Hidalgo, H; Feregrino, M; Higuera, F; Gomez, W H; Romero, J L; Padierna, J; Geyne, A; Ayers, M S

    1998-01-01

    Sixty-six patients with human immunodeficiency virus infection and diarrhoea caused by Cryptosporidium parvum were enrolled in a double-'blind' placebo-controlled study to evaluate the safety and efficacy of nitazoxanide in the treatment of cryptosporidiosis related to the acquired immune deficiency syndrome. Patients were randomly assigned to one of 3 treatment groups and received either 500 mg twice daily of nitazoxanide, 1000 mg twice daily of nitazoxanide, or placebo orally for 14 d; the patients on nitazoxanide then crossed over to placebo while the placebo patients crossed over to nitazoxanide therapy at either the high or low dose depending on their randomization. Three post-treatment faecal examinations were conducted on days 15, 22 and 29 following initiation of treatment: patients were considered 'cured' if none revealed any C. parvum oocysts. Both doses of nitazoxanide produced parasitological cure rates superior to the placebo responses (12/19 [63%, P = 0.016] for patients receiving 1 g/d and 10/15 [67%, P = 0.013] for those receiving 2 g/d). Parasitological cure was correlated with the complete resolution of the diarrhoeal syndrome in 19 of the 22 treated patients who were considered parasitologically cured (86%). Both doses of nitazoxanide were well tolerated by the patients.

  9. Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study.

    Science.gov (United States)

    Olmedilla-Alonso, B; Granado-Lorencio, F; Herrero-Barbudo, C; Blanco-Navarro, I; Blázquez-García, S; Pérez-Sacristán, B

    2008-04-01

    Diet and lifestyle are modifiable factors involved in the development and prevention of non-communicable diseases, including cardiovascular disease. Nut consumption, particularly walnut intake, has been inversely related to incident coronary heart disease (CHD) in observational studies and to improved lipid profiles in short-term feeding trials. To assess the potential functional effect associated with the regular consumption of walnut-enriched restructured meat products in subjects at risk for cardiovascular disease (CVD). A crossover single-dose bioavailability study (n = 3) using gamma-tocopherol as exposure marker and a crossover unblinded dietary intervention study (5 weeks) in subjects at risk (n = 25). Dietary intervention consisted of regular consumption of the meat product, with or without walnuts, five times per week for five weeks with a 1-month washout in between. Overnight fasting blood samples were collected on days 0, 12, 21, 28 and 35, coinciding with blood pressure and body weight recordings. Participants were asked to complete a diet record throughout the study. The functional effects were assessed using clinically relevant and related biomarkers of CHD: serum total, HDL and LDL cholesterol, triacylglycerols, homocysteine, vitamins B(6) and B(12), folic acid, alpha-tocopherol and platelet function test (obturation time). The regular consumption of walnut-enriched meat products compared with that of the restructured meat products without added walnuts provokes a decrease in total cholesterol of 6.8 mg/dl (CI(95%): -12.8, -0.85). Compared to baseline (mixed diet), meat products with walnuts decreased total cholesterol (-10.7 mg/dl, CI(95%): -17.1, -4.2), LDL cholesterol (-7.6 mg/dl, CI(95%): -2.2, -13.0) and body weight (-0.5 kg, CI(95%): -0.1, -0.9) and increased gamma-tocopherol (8.9 mg/dl, CI(95%): 1.0, 16.8). The restructured meat products with added walnuts supplied in this study can be considered functional foods for subjects at high risk for

  10. The study protocol of a blinded randomised-controlled cross-over trial of lavender oil as a treatment of behavioural symptoms in dementia

    Science.gov (United States)

    2010-01-01

    Background The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out) are stressful to both nursing home residents and their carers and are difficult to treat. Increasingly more attention is being paid to alternative interventions that are associated with fewer risks than pharmacology. Lavandula angustifolia (lavender) has been thought, for centuries, to have soothing properties, but the existing evidence is limited and shows mixed results. The aim of the current study is to test the effectiveness of topically applied pure lavender oil in reducing actual counts of challenging behaviours in nursing home residents. Methods/Design We will use a blinded repeated measures design with random cross-over between lavender oil and placebo oil. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to lavender or placebo blocks for one week then switched to the other condition for the following week. In each week the oils will be applied on three days with at least a two-day wash out period between conditions. Trained observers will note presence of target behaviours and predominant type of affect displayed during the 30 minutes before and the 60 minutes after application of the oil. Nursing staff will apply 1 ml of 30% high strength essential lavender oil to reduce the risk of missing a true effect through under-dosing. The placebo will comprise of jojoba oil only. The oils will be identical in appearance and texture, but can easily be identified by smell. For blinding purposes, all staff involved in applying the oil or observing the resident will apply a masking cream containing a mixture of lavender and other essential oils to their upper lip. In addition, nursing staff will wear a nose clip during the few minutes it takes to massage the oil to the resident's forearms. Discussion If our results show

  11. Synthetic food colourings and 'hyperactivity': a double-blind crossover study.

    Science.gov (United States)

    Rowe, K S

    1988-04-01

    Of 220 children referred for suspected 'hyperactivity', 55 were subjected to a 6 week trial of the Feingold diet. Forty (72.7%) demonstrated improved behaviour and 26 (47.3%) remained improved following liberalization of the diet over a period of 3-6 months. The parents of 14 children claimed that a particular cluster of behaviours was associated with the ingestion of foods containing synthetic colourings. A double-blind crossover study, employing a single-subject repeated measures design was conducted, using eight of these children. Subjects were maintained on a diet free from synthetic additives and were challenged daily for 18 weeks with either placebo (during lead-in and washout periods) or 50 mg of either tartrazine or carmoisine, each for 2 separate weeks. Two significant reactors were identified whose behavioural pattern featured extreme irritability, restlessness and sleep disturbance. One of the reactors did not have inattention as a feature. The findings raise the issue of whether the strict criteria for inclusion in studies concerned with 'hyperactivity' based on 'attention deficit disorder' may miss children who indicate behavioural changes associated with the ingestion of food colourings. Moreover, for further studies, the need to construct a behavioural rating instrument specifically validated for dye challenge is suggested.

  12. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

    2016-11-01

    Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

  13. ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study

    NARCIS (Netherlands)

    Lansbergen, M.M.; Dongen-Boomsma, M. van; Buitelaar, J.K.; Slaats-Willemse, D.I.E.

    2011-01-01

    Electroencephalography (EEG)-neurofeedback has been shown to offer therapeutic benefits to patients with attention-deficit/hyperactivity disorder (ADHD) in several, mostly uncontrolled studies. This pilot study is designed to test the feasibility and safety of using a double-blind placebo

  14. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.

    LENUS (Irish Health Repository)

    Phelan, Niamh

    2012-02-01

    BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES: We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN: We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS: Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS: Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was

  15. Eustress and Malondialdehyde (MDA): Role of Panax Ginseng: Randomized Placebo Controlled Study.

    Science.gov (United States)

    Al-Kuraishy, Hayder M; Al-Gareeb, Ali I

    2017-07-01

    Objective: The present study aimed at evaluating the effect of Panax Ginseng on malondialdehyde (MDA) serum levels during eustress on healthy volunteers. Method: In this study, 65 healthy volunteers were recruited from students of a medical school, with the mean age of 22.61±3.63 years. The volunteers were divided into 2 groups: Group A included 35 participants who were treated by Panax Ginseng 500 mg/day, which was regarded as the treated group; group B included 30 participants treated by placebo 500 mg/day, which was regarded as the control group. Baseline data were obtained and then one month after the study, the participants were followed with respect to induction of psychological stress through daily psychomotor performance task and visual working memory accuracy testing. Stress was assessed by malondialdehyde (MDA) serum levels. Results: The participants in the control group showed significant increases in MDA serum levels (p = 0.0004), which were related to significant increases in perceived stress scale from pstress scale (p = 0.02). Conclusion: Panax Ginseng produced significant reduction in oxidative stress and augmented eustress level in healthy volunteers 1 month after therapy.

  16. Minoxidil 2% lotion for eyebrow enhancement: a randomized, double-blind, placebo-controlled, spilt-face comparative study.

    Science.gov (United States)

    Lee, Saridpong; Tanglertsampan, Chuchai; Tanchotikul, Mingkwan; Worapunpong, Nigun

    2014-02-01

    Topical minoxidil has been successfully used to treat androgenetic alopecia. It can also be applied to enhance eyebrows. However, there is no study comparing minoxidil lotion with placebo for eyebrow enhancement. In this trial, we determined the efficacy and safety of minoxidil 2% lotion for eyebrow enhancement compared with placebo. Forty patients were randomized for minoxidil on the eyebrow on one side of the face and placebo on the other. Efficacy was evaluated by global photographic assessment, eyebrow diameter, eyebrow count and subject's satisfaction. Side-effects were also evaluated. Thirty-nine patients (97.5%) completed the study. After 16 weeks, the minoxidil group achieved significantly better results in all measured outcomes compared to the placebo group. Side-effects were minor and did not preclude patients from continuing the study. Our study suggests that minoxidil 2% lotion is a safe and effective treatment for eyebrow hypotrichosis. © 2014 Japanese Dermatological Association.

  17. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy.

    Science.gov (United States)

    Wood, Robert A; Kim, Jennifer S; Lindblad, Robert; Nadeau, Kari; Henning, Alice K; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A

    2016-04-01

    Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy because benefits usually diminish when treatment is discontinued. We sought to examine whether the addition of omalizumab to milk OIT reduces treatment-related reactions, improves outcomes, or both. This was a double-blind, placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label milk OIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22 to 40 weeks, followed by daily maintenance dosing through month 28. At month 28, omalizumab was discontinued, and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with rechallenge at month 32 to assess sustained unresponsiveness (SU). Fifty-seven subjects (7-32 years) were randomized, with no significant baseline differences in age, milk-specific IgE levels, skin test results, or OFC results. At month 28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10-g "desensitization" OFC (P = .18). At month 32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (P = .42). Adverse reactions were markedly reduced during OIT escalation in omalizumab-treated subjects for percentages of doses per subject provoking symptoms (2.1% vs 16.1%, P = .0005), dose-related reactions requiring treatment (0.0% vs 3.8%, P = .0008), and doses required to achieve maintenance (198 vs 225, P = .008). In this first randomized, double-blind, placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety but not in outcomes of efficacy (desensitization and SU). Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study.

    Science.gov (United States)

    Dower, James I; Geleijnse, Johanna M; Kroon, Paul A; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C H

    2016-11-01

    Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. In a randomized crossover study, twenty healthy men (40-80 years) were supplemented with: (1) 70g dark chocolate (150 mg epicatechin) with placebo capsules; (2) pure epicatechin capsules (2 × 50 mg epicatechin) with 75g white chocolate; and (3) placebo capsules with 75 g white chocolate (0 mg epicatechin). Vascular function (flow-mediated dilation (FMD) and augmentation index (AIx)) were measured before and 2 hours after interventions. Epicatechin metabolites time-profiles were measured in blood to calculate the bioavailability. Pure epicatechin did not significantly improve FMD (+0.75%; p = 0.10) or AIx (-2.2%; p = 0.23) compared to placebo. Dark chocolate significantly improved FMD (+0.96%; p = 0.04) and AIx (-4.6%; p = 0.02). Differences in improvements in FMD (+ 0.21%; p = 0.65) or Aix (-2.4%; p = 0.20) between pure epicatechin and dark chocolate were not significant. The bioavailability of epicatechin did not differ between pure epicatechin and dark chocolate (p = 0.14). Despite differences in epicatechin dose, improvements in vascular function after pure epicatechin and chocolate were similar and the bioavailability did not differ, suggesting a role for epicatechin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning

    Science.gov (United States)

    Świder, Karolina; Bąbel, Przemysław

    2016-01-01

    Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy. PMID:27362552

  20. The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: a double blind within-subject cross-over experiment.

    Directory of Open Access Journals (Sweden)

    Youl-Ri Kim

    Full Text Available BACKGROUND AND AIM: Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. METHOD: A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. RESULTS: Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group. Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. CONCLUSION: Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.

  1. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    Science.gov (United States)

    Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

    2011-01-01

    Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

  2. Atenolol vs. propranolol in essential tremor. A controlled, quantitative study.

    Science.gov (United States)

    Larsen, T A; Teräväinen, H; Calne, D B

    1982-11-01

    The beta-1 selective, hydrophilic adrenoceptor blocking drug atenolol (100 mg daily) was compared to the non-selective, lipid-soluble beta-blocker propranolol (240 mg daily), and to placebo, in a double-blind cross-over study in 24 patients with essential tremor. Atenolol and propranolol caused a similar decrease in heart rate. Both beta-blockers also suppressed the tremor intensity; there was no significant difference between them, but both were significantly better than placebo. These drugs did not affect tremor frequency. Twelve of the patients preferred propranolol subjectively, one preferred atenolol and none preferred placebo. No marked side-effects were observed. It was concluded that atenolol and other cardio-selective blockers offer an alternative for patients unable to tolerate the non-selective drugs. The site of action and receptor sub-type involved have still to be determined.

  3. The joy of six: how to control your crossovers.

    Science.gov (United States)

    Globus, Samuel T; Keeney, Scott

    2012-03-30

    Meiotic cells tightly regulate the number and distribution of crossovers to promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan-specific, cyclin-like protein that is crucial for crossover formation. They utilize this protein's unique properties to explore a remarkable example of biological numerology, whereby nearly every meiotic cell in C. elegans makes precisely six crossovers, one for each of its six chromosome pairs. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. A randomized placebo-controlled study of noninvasive cortical electrostimulation in the treatment of fibromyalgia patients.

    Science.gov (United States)

    Hargrove, Jeffrey B; Bennett, Robert M; Simons, David G; Smith, Susan J; Nagpal, Sunil; Deering, Donald E

    2012-01-01

    The aim of this multicenter study was to evaluate the efficacy, safety, and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia (FM). A prospective, randomized, double-blind, placebo-controlled design was used. Setting.  Subjects received therapy at two different outpatient clinical locations. There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM. Intervention.  Thirty-nine (39) active treatment (AT) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period. The primary outcome measures were the number of tender points (TePs) and pressure pain threshold (PPT). Secondary outcome measures were responses to the Fibromyalgia Impact Questionnaire (FIQ), Symptom Checklist-90 (SCL-90), Beck Depression Inventory-II, and a novel sleep questionnaire, all evaluated at baseline and at the end of treatment. Intervention provided significant improvements in TeP measures: compared with placebo, the AT patients improved in the number of positive TePs (-7.4 vs -0.2, PFIQ score (-15.5 vs -5.6, P=0.03), FIQ pain (-2.0 vs -0.6, P=0.03), FIQ fatigue (-2.0 vs -0.4, P=0.02), and FIQ refreshing sleep (-2.1 vs -0.7, P=0.02); and while FIQ function improved (-1.0 vs -0.2), the between-group change had a 14% likelihood of occurring due to chance (P=0.14). There were no significant side effects observed. Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain, TeP measures, fatigue, and sleep; and the treatment was well tolerated. This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients. Wiley Periodicals, Inc.

  5. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.

    Science.gov (United States)

    Ringman, John M; Frautschy, Sally A; Teng, Edmond; Begum, Aynun N; Bardens, Jenny; Beigi, Maryam; Gylys, Karen H; Badmaev, Vladimir; Heath, Dennis D; Apostolova, Liana G; Porter, Verna; Vanek, Zeba; Marshall, Gad A; Hellemann, Gerhard; Sugar, Catherine; Masterman, Donna L; Montine, Thomas J; Cummings, Jeffrey L; Cole, Greg M

    2012-01-01

    Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex(®) with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex(®) was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between

  6. Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.

    Science.gov (United States)

    Levkovitz, Yeciel; Tedeschini, Enrico; Papakostas, George I

    2011-04-01

    The authors sought to determine the efficacy of antidepressants in dysthymic disorder and to compare antidepressant and placebo response rates between major depressive disorder (MDD) and dysthymic disorder. PubMed/MEDLINE databases were searched for double-blind, randomized, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD or dysthymic disorder. We defined antidepressants as those with a letter of approval by the US, Canadian, or European Union drug regulatory agencies for treatment of MDD or dysthymic disorder, which included the following: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, ritanserin, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. Eligible studies were identified by cross-referencing the search term placebo with each of the above-mentioned agents. The search was limited to articles published between January 1, 1980, and November 20, 2009 (inclusive). To expand our database, we also reviewed the reference lists of the identified studies. We selected randomized, double-blind, placebo-controlled trials of antidepressants for either MDD or dysthymic disorder according to preset criteria relating to comorbidities, patient age, drug formulation, study duration, diagnostic criteria, choice of assessment scales, and whether or not the study reported original data. Final selection of articles was determined by consensus among the authors. A total of 194 studies were found that were eligible for inclusion in our analysis. Of these, 177 focused on the treatment of MDD and 17 on the treatment of dysthymic disorder. We found that

  7. Efficacy of ginger for prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving adriamycin-cyclophosphamide regimen: a randomized, double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Thamlikitkul, Lucksamon; Srimuninnimit, Vichien; Akewanlop, Charuwan; Ithimakin, Suthinee; Techawathanawanna, Sirisopa; Korphaisarn, Krittiya; Chantharasamee, Jomjit; Danchaivijitr, Pongwut; Soparattanapaisarn, Nopadol

    2017-02-01

    The purpose of this study is to determine the efficacy of ginger for reducing chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients receiving adriamycin and cyclophosphamide (AC) regimens. We enrolled breast cancer patients receiving AC who experienced moderate to severe nausea or vomiting during the first chemotherapy cycle. Subjects were randomized to receive a 500-mg ginger capsule or placebo twice a day for 5 days starting on the first day of the second AC cycle and were switched to the other treatment in the third cycle. All participants also received ondansetron and dexamethasone for CINV prophylaxis. Nausea severity was recorded once a day during the first 5 days of each cycle. The primary outcome was reduction in nausea score. Thirty-four subjects (68 cycles of AC) were enrolled. Mean (range) maximum nausea score in the first AC cycle was 58 (40-90). Thirty-three subjects (97 %) received the same AC doses in the second as in the third cycle. Mean (±standard error) maximum nausea scores in patients receiving ginger and placebo were 35.36 (±4.43) and 32.17 (±3.71), respectively. The difference in mean maximum nausea scores was 3 (95 % confidence interval, -3 to 9; P = 0.3). There were no significant differences between ginger and placebo in terms of vomiting incidence and severity, rescue medication use, chemotherapy compliance, and adverse events. Ginger (500 mg) twice daily was safe, but conferred no additional benefit in terms of reducing nausea severity in breast cancer patients receiving AC and ondansetron and dexamethasone for CINV prophylaxis.

  8. Double blind placebo controlled exposure to molds

    DEFF Research Database (Denmark)

    Meyer, H W; Jensen, K A; Nielsen, K F

    2005-01-01

    non-significant, and at the same level as after placebo exposure. The developed exposure system based on the Particle-Field and Laboratory Emission Cell (P-FLEC) makes it possible to deliver a precise and highly controlled dose of mold spores from water-damaged building materials, imitating realistic......The objective was to develop an experimental setup for human exposure to mold spores, and to study the clinical effect of this exposure in sensitive subjects who had previously experienced potentially building-related symptoms (BRS) at work. From three water-damaged schools eight employees....... In conclusion this is, to our knowledge, the first study to successfully conduct a human exposure to a highly controlled dose of fungal material aerosolized directly from wet building materials. This short-term exposure to high concentrations of two different molds induced no more reactions than exposure...

  9. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China.

    Science.gov (United States)

    He, Zhong; Chen, Rong; Zhou, Yingfang; Geng, Li; Zhang, Zhenyu; Chen, Shuling; Yao, Yanjun; Lu, Junli; Lin, Shouqing

    2009-05-20

    To investigate the efficacy and safety of VAC BNO 1095 extract in Chinese women suffering from moderate to severe premenstrual syndrome (PMS). Prospective, double-blind, placebo controlled, parallel-group, multi-center clinical trial design was employed. After screening and preparation phase lasting three cycles, Eligible patients were randomly assigned into treatment or placebo groups and had treatment with VAC extract or placebo for up to three cycles. Efficacy was assessed using the Chinese version PMS-diary (PMSD) and PMTS. Two hundred and seventeen women were eligible to enter the treatment phase (TP) and were randomly assigned into the treatment group (108) or the placebo group (109), 208 provided the efficacy data (treatment 104, placebo 104), and 202 completed the treatment phase (treatment 101, placebo 101). The mean total PMSD score decreased from 29.23 at baseline (0 cycle) to 6.41 at the termination (3rd cycle) for the treatment group and from 28.14 at baseline (0 cycle) to 12.64 at the termination (3rd cycle) for the placebo group. The total PMSD score of 3rd cycle was significantly lower than the baseline in both groups (pVitex agnus castus (VAC BNO 1095 corresponding to 40mg herbal drug) is a safe, well tolerated and effective drug of the treatment for Chinese women with the moderate to severe PMS.

  10. Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

    Science.gov (United States)

    Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

    2016-09-01

    α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

  11. Treatment of knee osteoarthritis with pulsed electromagnetic fields: a randomized, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Thamsborg, G; Florescu, A; Oturai, P

    2005-01-01

    OBJECTIVE: The investigation aimed at determining the effectiveness of pulsed electromagnetic fields (PEMF) in the treatment of osteoarthritis (OA) of the knee by conducting a randomized, double-blind, placebo-controlled clinical trial. DESIGN: The trial consisted of 2h daily treatment 5 days per...

  12. The use of placebo control in clinical trials: An overview of the ...

    African Journals Online (AJOL)

    The use of placebo control in clinical trials: An overview of the ethical issues involved for the protection of human research participants. ... A placebo looks exactly like the experimental drugs in every respect both in appearance and wrappings ...

  13. A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study

    Science.gov (United States)

    Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O'Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

    2011-01-01

    Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive…

  14. Improvement of walking distance by defibrotide in patients with intermittent claudication--results of a randomized, placebo-controlled study (the DICLIS study). Defibrotide Intermittent CLaudication Italian Study.

    Science.gov (United States)

    Violi, F; Marubini, E; Coccheri, S; Nenci, G G

    2000-05-01

    Defibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide. DICLIS was a double blind, placebo-controlled study which included patients with walking distance autonomy at a standardized treadmill test or =100 meters. A total of 310 patients were randomly allocated to placebo (n = 101), defibrotide 800 mg/day (n = 104) or defibrotide 1200 mg/day (n = 105). During a one year follow-up, the Absolute Walking Distance (AWD) was measured six times (0, 30, 60, 90, 180, 360 days). Similar improvement in walking distance was found in the three groups until the 90th day; thereafter placebo group showed no further increase, while AWD continued to increase in the defibrotide groups. Between the 180th and 360th day visits, AWD was significantly higher (P defibrotide than in patients given placebo. No difference in efficacy was observed between the two dosages of defibrotide. No differences in side effects were observed among the three groups. The results of the present trial suggest that long-term administration of defibrotide improves walking distance in patients with intermittent claudication.

  15. Effects of a Worksite Weight-Control Programme in Obese Male Workers: A Randomized Controlled Crossover Trial

    Science.gov (United States)

    Iriyama, Yae; Murayama, Nobuko

    2014-01-01

    Objective: We conducted a randomized controlled crossover trial to evaluate the effects of a new worksite weight-control programme designed for men with or at risk of obesity using a combination of nutrition education and nutrition environmental interventions. Subjects and methods: Male workers with or at risk of obesity were recruited for this…

  16. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study.

    Science.gov (United States)

    Stracke, H; Gaus, W; Achenbach, U; Federlin, K; Bretzel, R G

    2008-11-01

    Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

  17. Memantine enhances the effect of olanzapine in patients with schizophrenia: A randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Ahmad Fakhri

    2016-12-01

    Full Text Available Glutamate dysregulation may be involved in the neuropathology of schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a partial uncompetitive NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to olanzapine in patients with schizophrenia. In this double-blind, placebo-controlled studies, patients with schizophrenia according to DSM-IV clinical criteria were selected. Patients were randomly assigned to receive either memantine (week 1:10 mg/day; weeks 2-6:20 mg/day plus olanzapine (15-20 mg/day or olanzapine plus placebo. At baseline, no statistically significant difference regarding the mean total PANSS scores between treatment groups was found. Results showed that memantine significantly improved the positive and negative PANSS score in patients maintained on olanzapine after six weeks compared to olanzapine alone (P<0.001. Furthermore, female patients showed significantly better response than males, especially in positive PANSS score. No significant changes in extrapyramidal symptoms were observed.These findings indicate that olanzapine efficacy might be augmented with memantine. Furthermore, this effect is more remarkable in female patients with schizophrenia.

  18. Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration

    DEFF Research Database (Denmark)

    Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

    2017-01-01

    groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications...... with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). Results The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0–2), 0.5% (0–1%). We identified...

  19. Creatine fails to augment the benefits from resistance training in patients with HIV infection: a randomized, double-blind, placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Giorgos K Sakkas

    Full Text Available Progressive resistance exercise training (PRT improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance. The main outcome measurements included muscle strength (one repetition maximum, energetics ((31P magnetic resonance spectroscopy, composition and size (magnetic resonance imaging, as well as total body composition (dual-energy X-ray absorptiometry. Thirty-three subjects completed the study (17 creatine, 16 placebo. Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9% in creatine and placebo, respectively. There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved

  20. [Dietary supplementation of obese children with 1000 mg alpha-linolenic acid per day: a placebo-controlled double blind study].

    Science.gov (United States)

    Lohner, Szimonetta; Marosvölgyi, Tamás; Burus, István; Schmidt, János; Molnár, Dénes; Decsi, Tamás

    2007-08-12

    Enhanced dietary intake of omega-3 fatty acids may benefit persons with increased cardiovascular risk, among them obese subjects. Incorporation of omega-3 fatty acids into the plasma lipids is a prerequisite to achieve the favorable effects; however, only very few data are available on the dose of omega-3 fatty acid supplementation in children. The aim of our study was to examine the effects of the consumption of a diet supplemented with 1000 mg alpha-linolenic acid daily on plasma lipids in obese children. In this two times six-week-long, placebo-controlled, crossover study, 9 obese children (age: 13.1 [2.5] years, body mass index: 31.2 [6.2] kg/m 2 ), median [IQR]) incorporated into their diet one egg and one meatball (50 g) per day from hens fed diets containing flaxseed oil, i.e. supplementary dietary intake of 1000 mg alpha-linolenic acid per day was provided. The fatty acid composition of plasma lipids was determined by high-resolution gas-liquid chromatography. Tendencies of increase were observed in the alpha-linolenic acid content of plasma lipids in the phospholipid, triacyl-glycerine and sterol-ester fractions after the supplementation with alpha-linolenic acid. In the non-esterified fatty acid fraction, the values of alpha-linolenic acid were significantly higher after the supplementation (0.11 [0.08] versus 0.14 [0.20], % weight/weight, p < 0.05), indicating the beginning of the accumulation of alpha-linolenic acid in plasma lipids. In obese children a six-week-long supplementation of the diet with 1000 mg alpha-linolenic acid per day increased significantly the contribution of omega-3 fatty acids only to the non-esterified fatty acids of plasma lipids, but had no significant effect on the esterified fractions. Increase of the dose of supplementation may be needed to influence omega-3 fatty acid status in obese children.

  1. Erotic stimulus processing under amisulpride and reboxetine: a placebo-controlled fMRI study in healthy subjects.

    Science.gov (United States)

    Graf, Heiko; Wiegers, Maike; Metzger, Coraline D; Walter, Martin; Grön, Georg; Abler, Birgit

    2014-10-31

    Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  2. Weight Maintenance with Litramine (IQP-G-002AS: A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Barbara Grube

    2015-01-01

    Full Text Available Background. Litramine (IQP-G-002AS was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day or a matching placebo. Primary endpoints were difference of mean body weight (kg between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (-0.62±1.55 kg versus 1.62±1.48 kg, p<0.001. More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387.

  3. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone.

    Science.gov (United States)

    Waldinger, M D; Zwinderman, A H; Olivier, B

    2001-06-01

    Antidepressant medication is often associated with sexual side effects. A double-blind, placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin (5-HT) reuptake inhibitors--paroxetine and sertraline--and the 5-HT2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate. Forty-eight men with an intravaginal ejaculation latency time (IELT) of a maximum of 1 minute were randomly assigned to receive paroxetine (20 mg/day), sertraline (50 mg/day), nefazodone (400 mg/day), or placebo for 6 weeks. During the 1-month baseline and 6-week treatment period, IELTs were measured at home with a stopwatch. The trial was completed by 40 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was stable at approximately 20 seconds. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.002); the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds, respectively, compared with 28 seconds in the nefazodone group. The paroxetine and sertraline groups differed significantly (p < 0.001 and p = 0.024, respectively) from placebo, but the nefazodone group did not (p = 0.85). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, whereas sertraline delayed it only moderately. There was no clinically relevant delay in ejaculation with nefazodone.

  4. Effect of GutGard in the Management of Helicobacter pylori: A Randomized Double Blind Placebo Controlled Study

    Directory of Open Access Journals (Sweden)

    Sreenivasulu Puram

    2013-01-01

    Full Text Available A randomized, double blind placebo controlled study was conducted to evaluate the efficacy of GutGard (root extract of Glycyrrhiza glabra in the management of Helicobacter pylori (H. pylori gastric load. Participants diagnosed with H. pylori infection were randomly assigned to two groups to orally receive 150 mg of GutGard (n=55 or placebo (n=52 once daily for 60 days. H. pylori infection was assessed using 13C-urea breath test (13C-UBT at days 0, 30, and 60. Stool Antigen test (HpSA was also performed on days 0, 30, and 60. Repeated measures of analysis of variance (RMANOVA, chi-square, and Fisher's exact probability tests were used to compare the treatment outcomes. A significant interaction effect between group and time (P=0.00 and significant difference in mean Delta Over Baseline (DOB values between GutGard (n=50 and placebo (n=50 treated groups after intervention period were observed. On day 60, the results of HpSA test were negative in 28 subjects (56% in GutGard treated group whereas in placebo treated group only 2 subjects (4% showed negative response; the difference between the groups was statistically significant. On day 60, the results of 13C-UBT were negative in 24 (48% in GutGard treated group and the difference between the groups was statistically significant. The findings suggest GutGard is effective in the management of H. pylori.

  5. Mood Predicts Response to Placebo CPAP

    Directory of Open Access Journals (Sweden)

    Carl J. Stepnowsky

    2012-01-01

    Full Text Available Study Objectives. Continuous positive airway pressure (CPAP therapy is efficacious for treating obstructive sleep apnea (OSA, but recent studies with placebo CPAP (CPAP administered at subtherapeutic pressure have revealed nonspecific (or placebo responses to CPAP treatment. This study examined baseline psychological factors associated with beneficial effects from placebo CPAP treatment. Participants. Twenty-five participants were studied with polysomnography at baseline and after treatment with placebo CPAP. Design. Participants were randomized to either CPAP treatment or placebo CPAP. Baseline mood was assessed with the Profile of Mood States (POMS. Total mood disturbance (POMS-Total was obtained by summing the six POMS subscale scores, with Vigor weighted negatively. The dependent variable was changed in apnea-hypopnea index (ΔAHI, calculated by subtracting pre- from post-CPAP AHI. Negative values implied improvement. Hierarchical regression analysis was performed, with pre-CPAP AHI added as a covariate to control for baseline OSA severity. Results. Baseline emotional distress predicted the drop in AHI in response to placebo CPAP. Highly distressed patients showed greater placebo response, with a 34% drop (i.e., improvement in AHI. Conclusion. These findings underscore the importance of placebo-controlled studies of CPAP treatment. Whereas such trials are routinely included in drug trials, this paper argues for their importance even in mechanical-oriented sleep interventions.

  6. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    Directory of Open Access Journals (Sweden)

    Dietlind L. Wahner-Roedler

    2011-01-01

    Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

  7. Paracetamol 325 mg/tramadol 37.5 mg effect on pain during needle electromyography: a double-blind crossover clinical trial.

    Science.gov (United States)

    Kalantar, Seyed Sadeq; Abbasi, Mehrshad; Faghihi-Kashani, Sara; Majedi, Hossein; Ahmadi, Mona; Agah, Elmira; Tafakhori, Abbas

    2016-12-01

    Needle insertion during electromyography (EMG) may cause varying levels of pain that could lead to inaccurate assessment and premature termination of the procedure. The aim of this study is to compare paracetamol 325 mg/tramadol 37.5 mg with placebo in relieving pain before EMG. This is a randomized, crossover, placebo-controlled, double-blind clinical trial; forty-four healthy individuals, including 27 males with a mean age of 35.3 years (range 18-59 years), entered this study. The needles were inserted unilaterally 2 h after administration of two analgesic tablets of paracetamol 325 mg/tramadol 37.5 mg or two placebo tablets. The pain was scored through a 100-mm visual analog scale (VAS) immediately and 2 h after the procedure. The side effects were also recorded. Within a week, the procedure was repeated on the other upper limb, changing the treatment and placebo. The immediate and 2-h VAS scores were notably lower after administration of treatment compared to placebo (immediate pain: 17.5 ± 12.8 vs. 32.1 ± 16.0, P pain: 1.6 ± 5.6 vs. 5.8 ± 7.9, P = 0. 002). There was a higher prevalence of side effects when treatment was used (48 vs. 9 %, P pain. Further application of this medication in patients with neuromuscular disorders would warrant additional clinical trials, particularly considering the adverse events.

  8. Placebo can enhance creativity.

    Science.gov (United States)

    Rozenkrantz, Liron; Mayo, Avraham E; Ilan, Tomer; Hart, Yuval; Noy, Lior; Alon, Uri

    2017-01-01

    The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition. Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency. The placebo group showed higher originality than the control group both in the CFG (pcreativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity.

  9. A double-blind, placebo-controlled study of the opiate antagonist, naltrexone, in the treatment of kleptomania.

    Science.gov (United States)

    Grant, Jon E; Kim, Suck Won; Odlaug, Brian L

    2009-04-01

    Kleptomania is a rare psychiatric disorder characterized by recurrent stealing and for which there exists no empirically validated treatments. This study examined the efficacy and tolerability of the opioid antagonist naltrexone in adults with kleptomania who have urges to steal. An 8-week, double-blind, placebo-controlled trial was conducted to evaluate the safety and efficacy of oral naltrexone for kleptomania. Twenty-five individuals with DSM-IV kleptomania were randomized to naltrexone (dosing ranging from 50 mg/day to 150 mg/day) or placebo. Twenty-three subjects (92%) completed the study. Subjects were assessed every 2 weeks with the Yale Brown Obsessive Compulsive Scale Modified for Kleptomania (K-YBOCS), the urge and behavior subscales of the K-YBOCS, the Kleptomania Symptom Assessment Scale (K-SAS), the Clinical Global Impressions Scale (CGI), and measures of depression, anxiety, and psychosocial functioning. Subjects assigned to naltrexone had significantly greater reductions in K-YBOCS total scores (p = .001), stealing urges (p = .032), and stealing behavior (p kleptomania severity (reflected in the CGI scores) (p kleptomania. Naltrexone was well tolerated.

  10. PACE - The first placebo controlled trial of paracetamol for acute low back pain: design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Day Richard O

    2010-07-01

    Full Text Available Abstract Background Clinical practice guidelines recommend that the initial treatment of acute low back pain (LBP should consist of advice to stay active and regular simple analgesics such as paracetamol 4 g daily. Despite this recommendation in all international LBP guidelines there are no placebo controlled trials assessing the efficacy of paracetamol for LBP at any dose or dose regimen. This study aims to determine whether 4 g of paracetamol daily (in divided doses results in a more rapid recovery from acute LBP than placebo. A secondary aim is to determine if ingesting paracetamol in a time-contingent manner is more effective than paracetamol taken when required (PRN for recovery from acute LBP. Methods/Design The study is a randomised double dummy placebo controlled trial. 1650 care seeking people with significant acute LBP will be recruited. All participants will receive advice to stay active and will be randomised to 1 of 3 treatment groups: time-contingent paracetamol dose regimen (plus placebo PRN paracetamol, PRN paracetamol (plus placebo time-contingent paracetamol or a double placebo study arm. The primary outcome will be time (days to recovery from pain recorded in a daily pain diary. Other outcomes will be pain intensity, disability, function, global perceived effect and sleep quality, captured at baseline and at weeks 1, 2, 4 and 12 by an assessor blind to treatment allocation. An economic analysis will be conducted to determine the cost-effectiveness of treatment from the health sector and societal perspectives. Discussion The successful completion of the trial will provide the first high quality evidence on the effectiveness of the use of paracetamol, a guideline endorsed treatment for acute LBP. Trail registration ACTRN12609000966291.

  11. Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study.

    Science.gov (United States)

    Donnenfeld, Eric D; Karpecki, Paul M; Majmudar, Parag A; Nichols, Kelly K; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P

    2016-06-01

    To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events.

  12. Effects of Low Dose Metformin in Adolescents with Type I Diabetes Mellitus: A Randomized, Double-Blinded Placebo-Controlled Study

    Science.gov (United States)

    Nadeau, Kristen; Chow, Kelsey; Alam, Lyla; Lindquist, Kara; Cambell, Sarah; McFann, Kim; Klingensmith, Georgeanna; Walravens, Phillipe

    2014-01-01

    Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, Setting, and Participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages 13–20 years) with T1DM. Participants were randomized to receive either metformin or placebo for six months. HbA1c, insulin dose, waist circumference, BMI, and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI Z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. PMID:24698216

  13. Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.

    Science.gov (United States)

    Halaska, M; Beles, P; Gorkow, C; Sieder, C

    1999-08-01

    In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 x 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS (n=48) and 10.6 mm/20.3 mm with placebo (n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo (p=0.018; p=0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of 'borderline significance' (p=0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS: n=5; placebo : n=4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.

  14. Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study.

    Science.gov (United States)

    Eid, Noura; Osmanova, Hristina; Natchez, Cecile; Walton, Gemma; Costabile, Adele; Gibson, Glenn; Rowland, Ian; Spencer, Jeremy P E

    2015-10-28

    The reported inverse association between the intake of plant-based foods and a reduction in the prevalence of colorectal cancer may be partly mediated by interactions between insoluble fibre and (poly)phenols and the intestinal microbiota. In the present study, we assessed the impact of palm date consumption, rich in both polyphenols and fibre, on the growth of colonic microbiota and markers of colon cancer risk in a randomised, controlled, cross-over human intervention study. A total of twenty-two healthy human volunteers were randomly assigned to either a control group (maltodextrin-dextrose, 37·1 g) or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d duration and was separated by a 14-d washout period in a cross-over manner. Changes in the growth of microbiota were assessed by fluorescence in situ hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further, ammonia concentrations, faecal water genotoxicity and anti-proliferation ability were also assessed using different assays, which included cell work and the Comet assay. Accordingly, dietary intakes, anthropometric measurements and bowel movement assessment were also carried out. Although the consumption of dates did not induce significant changes in the growth of select bacterial groups or SCFA, there were significant increases in bowel movements and stool frequency (Pfruit intake significantly reduced genotoxicity in human faecal water relative to control (Pfruit may reduce colon cancer risk without inducing changes in the microbiota.

  15. Validation and acceptability of double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Venter, Carina; Maslin, Kate; Patil, Veeresh; Grundy, Jane; Glasbey, Gillian; Raza, Abid; Vlieg-Boerstra, Berber; Dean, Taraneh

    2016-01-01

    The Double Blind Placebo Controlled Food Challenge (DBPCFC) is considered the gold standard for food allergy diagnosis (1, 2). It is recommended that active and placebo challenge foods for DBPCFCs are sufficiently blinded in terms of smell, flavour and texture. Difficulties arise with children

  16. Placebo can enhance creativity.

    Directory of Open Access Journals (Sweden)

    Liron Rozenkrantz

    Full Text Available The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition.Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45, and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45. Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG, and a randomly chosen subset (n = 57 also completed two manual standardized creativity tests, the alternate uses test (AUT and the Torrance test (TTCT. In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency.The placebo group showed higher originality than the control group both in the CFG (p<0.04, effect size = 0.5 and in the AUT (p<0.05, effect size = 0.4, but not in the Torrance test. The placebo group also found more shapes outside of the standard categories found by a set of 100 CFG players in a previous study, a feature termed out-of-the-boxness (p<0.01, effect size = 0.6.The findings indicate that placebo can enhance the originality aspect of creativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which

  17. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

    DEFF Research Database (Denmark)

    Orwoll, Eric; Teglbjærg, Christence S; Langdahl, Bente Lomholt

    2012-01-01

    Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study...... by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations....... Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P adverse events was similar between groups. Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases...

  18. Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Chizzola

    2000-03-01

    Full Text Available OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43±9 years, and their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016 as well as an increase in left ventricular shortening fraction (p=0.02 and in left ventricular ejection fraction (p=0.017 occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

  19. Effect of sodium bicarbonate on prolonged running performance: A randomized, double-blind, cross-over study.

    Directory of Open Access Journals (Sweden)

    Tanja Freis

    Full Text Available The ability to sustain intense exercise seems to be partially limited by the body's capability to counteract decreases in both intra- and extracellular pH. While the influence of an enhanced buffering capacity via sodium bicarbonate (BICA on short-term, high-intensity exercise performance has been repeatedly investigated, studies on prolonged endurance performances are comparatively rare, especially for running. The aim of the following study was to assess the ergogenic effects of an oral BICA substitution upon exhaustive intensive endurance running performance.In a double-blind randomized cross-over study, 18 trained runners (VO2peak: 61.2 ± 6.4 ml•min-1•kg-1 performed two exhaustive graded exercise tests and two constant load tests (30 main at 95% individual anaerobic threshold (IAT followed by 110% IAT until exhaustion after ingestion of either sodium bicarbonate (BICA (0.3 g/kg or placebo (4 g NaCl diluted in 700 ml of water. Time to exhaustion (TTE in the constant load test was defined as the main outcome measure. Throughout each test respiratory gas exchange measurements were conducted as well as determinations of heart rate, blood gases and blood lactate concentration.TTE in the constant load test did not differ significantly between BICA and placebo conditions (BICA: 39.6 ± 5.6 min, placebo: 39.3 ± 5.6 min; p = 0.78. While pH in the placebo test dropped to a slightly acidotic value two minutes after cessation of exercise (7.34 ± 0.05 the value in the BICA trial remained within the normal range (7.41 ± 0.06 (p < 0.001. In contrast, maximum running speed (Vmax in the exhaustive graded exercise test was significantly higher with BICA (17.4 ± 1.0 km/h compared to placebo (17.1 ± 1.0 km/h (p = 0.009. The numerical difference in maximum oxygen consumption (VO2peak failed to reach statistical significance (BICA: 61.2 ± 6.4 ml•min-1•kg-1, placebo: 59.8 ± 6.4 ml•min-1•kg-1; p = 0.31. Maximum blood lactate was significantly

  20. Effect of sodium bicarbonate on prolonged running performance: A randomized, double-blind, cross-over study.

    Science.gov (United States)

    Freis, Tanja; Hecksteden, Anne; Such, Ulf; Meyer, Tim

    2017-01-01

    The ability to sustain intense exercise seems to be partially limited by the body's capability to counteract decreases in both intra- and extracellular pH. While the influence of an enhanced buffering capacity via sodium bicarbonate (BICA) on short-term, high-intensity exercise performance has been repeatedly investigated, studies on prolonged endurance performances are comparatively rare, especially for running. The aim of the following study was to assess the ergogenic effects of an oral BICA substitution upon exhaustive intensive endurance running performance. In a double-blind randomized cross-over study, 18 trained runners (VO2peak: 61.2 ± 6.4 ml•min-1•kg-1) performed two exhaustive graded exercise tests and two constant load tests (30 main at 95% individual anaerobic threshold (IAT) followed by 110% IAT until exhaustion) after ingestion of either sodium bicarbonate (BICA) (0.3 g/kg) or placebo (4 g NaCl) diluted in 700 ml of water. Time to exhaustion (TTE) in the constant load test was defined as the main outcome measure. Throughout each test respiratory gas exchange measurements were conducted as well as determinations of heart rate, blood gases and blood lactate concentration. TTE in the constant load test did not differ significantly between BICA and placebo conditions (BICA: 39.6 ± 5.6 min, placebo: 39.3 ± 5.6 min; p = 0.78). While pH in the placebo test dropped to a slightly acidotic value two minutes after cessation of exercise (7.34 ± 0.05) the value in the BICA trial remained within the normal range (7.41 ± 0.06) (p < 0.001). In contrast, maximum running speed (Vmax) in the exhaustive graded exercise test was significantly higher with BICA (17.4 ± 1.0 km/h) compared to placebo (17.1 ± 1.0 km/h) (p = 0.009). The numerical difference in maximum oxygen consumption (VO2peak) failed to reach statistical significance (BICA: 61.2 ± 6.4 ml•min-1•kg-1, placebo: 59.8 ± 6.4 ml•min-1•kg-1; p = 0.31). Maximum blood lactate was significantly

  1. Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. The Scandinavian BPH Study Group

    DEFF Research Database (Denmark)

    Andersen, J T; Ekman, P; Wolf, H

    1995-01-01

    rate, prostate volume, postvoiding residual urinary volume, and serum concentrations of prostate-specific antigen together with laboratory safety parameters were measured at entry and at months 12 and 24. Interim physical and laboratory examinations were performed when indicated clinically. RESULTS......OBJECTIVES. To study if placebo-induced improvement in men with symptomatic benign prostatic hyperplasia (BPH) is maintained over 2 years, and to study the efficacy and safety from intervention with finasteride 5 mg for 24 months. METHODS. This was a multicenter, double-blind, placebo....... The maximum urinary flow rate decreased in the placebo group, but improved in the finasteride group, resulting in a between-group difference of 1.8 mL/s at 24 months (P prostate volume was +12% in the placebo group versus -19% in the finasteride-treated group (P

  2. Effect of Moringa oleifera Leaf Capsules on Glycemic Control in Therapy-Naïve Type 2 Diabetes Patients: A Randomized Placebo Controlled Study

    Directory of Open Access Journals (Sweden)

    Rutchaporn Taweerutchana

    2017-01-01

    Full Text Available Background. Studies showed effects of Moringa oleifera (MO on lowering blood sugar levels in animal and diabetes patients. The aims of this study were to determine the effect of MO leaf capsules on glucose control in therapy-naïve type 2 diabetes mellitus (T2DM and to evaluate its safety. Method. This was a prospective randomized placebo controlled study. Therapy-naïve T2DM was randomly assigned to receive either 8 grams per day of MO leaf capsules (MO leaf group or placebo for 4 weeks. Clinical and laboratory characteristics were recorded at screening and at the end of 4-week study. 9-point plasma glucose was obtained before and every week during the study. Results. Thirty-two T2DM patients were enrolled. The mean age was 55 years and the mean HbA1C was 7.0%. There was no significant difference in FPG and HbA1C between groups. MO leaf group had SBP reduction by 5 mmHg as compared to baseline but this difference had no statistical significance. There were no adverse effects of MO leaf. Conclusions. Moringa oleifera leaf had no effect on glycemic control and no adverse effects in T2DM. Interestingly, this study demonstrated that MO leaf had a tendency on blood pressure reduction in T2DM, and this result needs further investigation.

  3. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Vollmer, T L; Sorensen, P S; Selmaj, K

    2014-01-01

    The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores...... months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly...... reduced with laquinimod [-18 %, risk ratio (RR) = 0.82, 95 % CI 0.66-1.02; p = 0.075] vs. placebo. Laquinimod significantly reduced PBVC (28 %, p change in confirmed disability worsening with laquinimod measured...

  4. Systematic review of quality of life and functional outcomes in randomized placebo-controlled studies of medications for attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Coghill, David R; Banaschewski, Tobias; Soutullo, César; Cottingham, Matthew G; Zuddas, Alessandro

    2017-11-01

    Children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) experience functional impairment and poor health-related quality of life (HRQoL) in addition to symptoms of inattention/hyperactivity-impulsivity. To synthesize qualitatively the published evidence from randomized, double-blind, placebo-controlled trials of the effectiveness of pharmacotherapy on functional impairment or HRQoL in patients with ADHD, a systematic PubMed searching and screening strategy was designed to identify journal articles meeting pre-specified criteria. Post hoc analyses and meta-analyses were excluded. HRQoL outcomes, functional outcomes and the principal ADHD symptom-based outcome were extracted from included studies. An effect size of 0.5 versus placebo was used as a threshold for potential clinical relevance (unreported effect sizes were calculated when possible). Of 291 records screened, 35 articles describing 34 studies were included. HRQoL/functioning was usually self-rated in adults and proxy-rated in children/adolescents. Baseline data indicated substantial HRQoL deficits in children/adolescents. Placebo-adjusted effects of medication on ADHD symptoms, HRQoL and functioning, respectively, were statistically or nominally significant in 18/18, 10/12 and 7/9 studies in children/adolescents and 14/16, 9/11 and 9/10 studies in adults. Effect sizes were ≥0.5 versus placebo for symptoms, HRQoL and functioning, respectively, in 14/16, 7/9 and 4/8 studies in children/adolescents; and 6/12, 1/6 and 1/8 studies in adults. Effect sizes were typically larger for stimulants than for non-stimulants, for symptoms than for HRQoL/functioning, and for children/adolescents than for adults. The efficacy of ADHD medication extends beyond symptom control and may help reduce the related but distinct functional impairments and HRQoL deficits in patients with ADHD.

  5. The Association Between Urban Tree Cover and Gun Assault: A Case-Control and Case-Crossover Study.

    Science.gov (United States)

    Kondo, Michelle C; South, Eugenia C; Branas, Charles C; Richmond, Therese S; Wiebe, Douglas J

    2017-08-01

    Green space and vegetation may play a protective role against urban violence. We investigated whether being near urban tree cover during outdoor activities was related to being assaulted with a gun. We conducted geographic information systems-assisted interviews with boys and men aged 10-24 years in Philadelphia, Pennsylvania, including 135 patients who had been shot with a firearm and 274 community controls, during 2008-2011. Each subject reported a step-by-step mapped account of where and with whom they traveled over a full day from waking until being assaulted or going to bed. Geocoded path points were overlaid on mapped layers representing tree locations and place-specific characteristics. Conditional logistic regressions were used to compare case subjects versus controls (case-control) and case subjects at the time of injury versus times earlier that day (case-crossover). When comparing cases at the time of assault to controls matched at the same time of day, being under tree cover was inversely associated with gunshot assault (odds ratio (OR) = 0.70, 95% confidence interval (CI): 0.55, 0.88), especially in low-income areas (OR = 0.69, 95% CI: 0.54, 0.87). Case-crossover models confirmed this inverse association overall (OR = 0.55, 95% CI: 0.34, 0.89) and in low-income areas (OR = 0.54, 95% CI: 0.33, 0.88). Urban greening and tree cover may hold promise as proactive strategies to decrease urban violence. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study.

    Science.gov (United States)

    van de Loo, Aurora J A E; Bervoets, Adriana C; Mooren, Loes; Bouwmeester, Noor H; Garssen, Johan; Zuiker, Rob; van Amerongen, Guido; van Gerven, Joop; Singh, Jaskaran; der Ark, Peter Van; Fedgchin, Maggie; Morrison, Randall; Wajs, Ewa; Verster, Joris C

    2017-11-01

    The purpose of this study is to evaluate the single dose effect of intranasal esketamine (84 mg) compared to placebo on on-road driving performance. Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant drug is known to negatively affect driving performance. Twenty-six healthy volunteers aged 21 to 60 years were enrolled in this study. In the evening, 8 h after treatment administration, participants conducted the standardized 100-km on-road driving test. Primary outcome measure was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Mean lateral position, mean speed, and standard deviation of speed were secondary outcome measures. For SDLP, non-inferiority analyses were conducted, using +2.4 cm (relative to placebo) as a predefined non-inferiority margin for clinical relevant impairment. Twenty-four participants completed the study. No significant SDLP difference was found between esketamine and placebo (p = 0.7638), whereas the SDLP after mirtazapine was significantly higher when compared to placebo (p = 0.0001). The upper limit of the two-sided 95% confidence interval (CI) of the mean difference between esketamine and placebo was +0.86 cm, i.e., deviation of speed, and mean lateral position were observed between the active treatments and placebo. No significant difference in driving performance was observed 8 h after administering intranasal esketamine (84 mg) or placebo. In contrast, oral mirtazapine (30 mg) significantly impaired on road driving performance.

  7. Young Women's Ratings of Three Placebo Multipurpose Prevention Technologies for HIV and Pregnancy Prevention in a Randomized, Cross-Over Study in Kenya and South Africa.

    Science.gov (United States)

    Minnis, Alexandra M; Roberts, Sarah T; Agot, Kawango; Weinrib, Rachel; Ahmed, Khatija; Manenzhe, Kgahlisho; Owino, Fredrick; van der Straten, Ariane

    2018-03-20

    End-user input is critical to inform development of multipurpose prevention technology (MPT) products that prevent HIV and pregnancy. The TRIO Study, conducted in Kenya and South Africa, enrolled 277 HIV-negative women aged 18-30 in a randomized cross-over study to use each placebo MPT (daily oral tablets, monthly injections, and monthly vaginal ring) for one month. At the end of each month, participants rated how much they liked using the product on a 5-point Likert scale (5 = liked very much). We compared mean ratings using paired t-tests and examined sociodemographic-, attribute-, and behavior-related characteristics associated with ratings using multivariable linear regression and data from in-depth interviews. After use, mean ratings were significantly higher for injections [4.3 (SD = 1.0)] compared with tablets [3.0 (SD = 1.3)] and rings [3.3 (SD = 1.4)] (p < 0.001); mean ratings for rings were significantly higher than for tablets (p = 0.013). Mean ratings of a hypothetical active MPT increased for all products after the one-month period of use, with the greatest increase for rings, the least familiar product. In multivariable analysis, acceptability of key product attributes (e.g., product look) were associated with a significant increase of ≥ 1 point in the mean rating across all three products (p ≤ 0.001). Perceived ability to use the product without partner knowledge was associated with a higher mean rating for rings (b = 0.50; p = 0.006). The acceptability of product attributes contributed significantly to the rating of all products, highlighting the value of choice in pregnancy and HIV prevention to accommodate diverse users.

  8. A double-blind, randomized, placebo-controlled pilot trial to determine the efficacy and safety of ibudilast, a potential glial attenuator, in chronic migraine

    Directory of Open Access Journals (Sweden)

    Kwok YH

    2016-10-01

    Full Text Available Yuen H Kwok,1 James E Swift,1 Parisa Gazerani,2 Paul Rolan1 1Discipline of Pharmacology, University of Adelaide, Level 5 Medical School North, South Australia, Australia; 2Department of Health Science & Technology, Aalborg University, Aalborg, Denmark Background: Chronic migraine (CM is problematic, and there are few effective treatments. Recently, it has been hypothesized that glial activation may be a contributor to migraine; therefore, this study investigated whether the potential glial inhibitor, ibudilast, could attenuate CM. Methods: The study was of double-blind, randomized, placebo-controlled, two-period crossover design. Participants were randomized to receive either ibudilast (40 mg twice daily or placebo treatment for 8 weeks. Subsequently, the participants underwent a 4-week washout period followed by a second 8-week treatment block with the alternative treatment. CM participants completed a headache diary 4 weeks before randomization throughout both treatment periods and 4 weeks after treatment. Questionnaires assessing quality of life and cutaneous allodynia were collected on eight occasions throughout the study. Results: A total of 33 participants were randomized, and 14 participants completed the study. Ibudilast was generally well tolerated with mild, transient adverse events, principally nausea. Eight weeks of ibudilast treatment did not reduce the frequency of moderate to severe headache or of secondary outcome measures such as headache index, intake of symptomatic medications, quality of life or change in cutaneous allodynia. Conclusion: Using the current regimen, ibudilast does not improve migraine with CM participants. Keywords: chronic migraine, glia, ibudilast, headache, immune system

  9. Effects of Soluble Corn Fiber Alone or in Synbiotic Combination with Lactobacillus rhamnosus GG and the Pilus-Deficient Derivative GG-PB12 on Fecal Microbiota, Metabolism, and Markers of Immune Function: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Elderly (Saimes Study).

    Science.gov (United States)

    Costabile, Adele; Bergillos-Meca, Triana; Rasinkangas, Pia; Korpela, Katri; de Vos, Willem M; Gibson, Glenn R

    2017-01-01

    The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement. We investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor™ Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60-80 years) was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3 weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics. Consumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides . L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis . Oscillospira and Desulfovibrio slightly decreased in the L. rhamnosus GG combined with SCF group, whereas

  10. Individual cognitive behavioral therapy for insomnia in breast cancer survivors: a randomized controlled crossover pilot study

    Science.gov (United States)

    Fiorentino, Lavinia; McQuaid, John R; Liu, Lianqi; Natarajan, Loki; He, Feng; Cornejo, Monique; Lawton, Susan; Parker, Barbara A; Sadler, Georgia R; Ancoli-Israel, Sonia

    2010-01-01

    Purpose Estimates of insomnia in breast cancer patients are high, with reports of poor sleep lasting years after completion of cancer treatment. This randomized controlled crossover pilot study looked at the effects of individual cognitive behavioral therapy for insomnia (IND-CBT-I) on sleep in breast cancer survivors. Patients and methods Twenty-one participants were randomly assigned to either a treatment group (six weekly IND-CBT-I sessions followed by six weeks of follow up) or a delayed treatment control group (no treatment for six weeks followed by six weekly IND-CBT-I sessions). Of these, 14 participants completed the pilot study (six in the treatment group and eight in the delayed treatment control group). Results Self-rated insomnia was significantly improved in the treatment group compared to the waiting period in the delayed treatment control group. The pooled pre-post-IND-CBT-I analyses revealed improvements in self-rated insomnia, sleep quality, and objective measures of sleep. Conclusions These preliminary results suggest that IND-CBT-I is appropriate for improving sleep in breast cancer survivors. Individual therapy in a clinic or private practice may be a more practical option for this population as it is more easily accessed and readily available in an outpatient setting. PMID:23616695

  11. Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

    Science.gov (United States)

    Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

    2014-01-01

    Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are

  12. Rates of cognitive change in Alzheimer disease: Observations across a decade of placebo-controlled clinical trials with donepezil

    DEFF Research Database (Denmark)

    Jones, Roy W; Schwam, Elias; Wilkinson, David

    2009-01-01

    Treatment success in Alzheimer disease (AD) trials is generally based on benefits over placebo-treated controls. Consequently, variation in rates of decline among placebo-treated patients could impact outcomes from AD trials. In the present analyses, individual patient data [baseline Mini......-Mental State Examination (MMSE): 10 to 26] were pooled from randomized, placebo-controlled studies of donepezil for AD conducted during the 1990s, and grouped by initiation year-group 1: 1990 to 1994; group 2: 1996 to 1999. Changes in MMSE and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS...

  13. The study protocol of a blinded randomised-controlled cross-over trial of lavender oil as a treatment of behavioural symptoms in dementia

    Directory of Open Access Journals (Sweden)

    O'Connor Daniel W

    2010-07-01

    Full Text Available Abstract Background The agitated behaviours that accompany dementia (e.g. pacing, aggression, calling out are stressful to both nursing home residents and their carers and are difficult to treat. Increasingly more attention is being paid to alternative interventions that are associated with fewer risks than pharmacology. Lavandula angustifolia (lavender has been thought, for centuries, to have soothing properties, but the existing evidence is limited and shows mixed results. The aim of the current study is to test the effectiveness of topically applied pure lavender oil in reducing actual counts of challenging behaviours in nursing home residents. Methods/Design We will use a blinded repeated measures design with random cross-over between lavender oil and placebo oil. Persons with moderate to severe dementia and associated behavioural problems living in aged care facilities will be included in the study. Consented, willing participants will be assigned in random order to lavender or placebo blocks for one week then switched to the other condition for the following week. In each week the oils will be applied on three days with at least a two-day wash out period between conditions. Trained observers will note presence of target behaviours and predominant type of affect displayed during the 30 minutes before and the 60 minutes after application of the oil. Nursing staff will apply 1 ml of 30% high strength essential lavender oil to reduce the risk of missing a true effect through under-dosing. The placebo will comprise of jojoba oil only. The oils will be identical in appearance and texture, but can easily be identified by smell. For blinding purposes, all staff involved in applying the oil or observing the resident will apply a masking cream containing a mixture of lavender and other essential oils to their upper lip. In addition, nursing staff will wear a nose clip during the few minutes it takes to massage the oil to the resident's forearms

  14. Topical treatment of chronic venous ulcers with sucralfate: a placebo controlled randomized study.

    Science.gov (United States)

    Tumino, Giovanni; Masuelli, Laura; Bei, Roberto; Simonelli, Lucilla; Santoro, Alberto; Francipane, Silvana

    2008-07-01

    Venous leg ulcers are an important medical issue due to their high incidence in the elderly and the lack of a standard curative approach. Apart from surgical therapy, different medical treatments to effect ulcer wound repair and regeneration are currently being investigated. Sucralfate is a cytoprotective agent employed to prevent or treat several gastrointestinal diseases such as gastroesophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. In this study we evaluated the efficacy, safety and tolerability of topical sucralfate (SUC-LIS 95) on the healing of chronic venous leg ulcers in 50 patients by a double-blind, placebo-controlled, randomized study. Our results indicated that the daily application of SUC-LIS 95 to non-infected post-phlebitis/vascular ulcers, for a median period of 42.0 days, led to complete healing in 95.6% of patients, against only 10.9% of cases with a matched placebo. A significant improvement was obtained in the SUC-LIS 95-treated patient group with regard to local tissue inflammation as well as pain and burning, and consequently, in ulcer size and the evolution of granulation tissue. Our findings were corroborated for selected patients by the morphological analysis of biopsies obtained before and after treatment. Using ultrastructural analysis we demonstrated that the topical use of SUC-LIS 95 was able to affect neoangiogenesis, increase wound contraction, promote re-epithelialization of the wound area and diminish the inflammatory reaction. Overall, our results indicated that patients with chronic venous ulcers show improvement after the use of topical sucralfate.

  15. [Pharmacotherapy of attention deficit hyperactivity disorder in children: the results of a multicenter double-blind placebo-controlled study of hopantenic acid].

    Science.gov (United States)

    Zavadenko, N N; Suvorinova, N Yu; Vakula, I N; Malinina, E V; Kuzenkova, L M

    To assess the efficacy and safety of hopantenic acid (pantogam) compared to placebo in the treatment of attention deficit hyperactivity disorder (ADHD) in children, aged from 6 to 12 years, during 4 month in the prospective multicenter comparative double-blind placebo-controlled study in parallel groups. One hundred patients enrolled in the safety assessment population were stratified into two equal pantogam and placebo groups. Eighty-nine patients who completed the study in according to the protocol were included in the efficacy assessment group: 45 in the pantogam group and 44 in the placebo group. Pantogam was administered in tablets (250 mg) in the therapeutic dose 30 mg/kg of body mass, divided into 2 doses, during 4 month. Patient's state was assessed by the total score on ADHD-DSM-IV, CGI-S WFIRS-P and results of the Toulouse-Piéron test for sustained attention. There was a trend towards an increase in the percentage of patients with positive changes (a decrease in the total ADHD-DSM-IV by ≥25%) in the end of the 3rd and 4th month in the pantogam group (treatment response was 66.7 and 68.9%, respectively) compared to the placebo group (treatment response was 52.3 and 61.4%, respectively). A significant decrease in disease severity assessed by the CGI-S was noted in the pantogam group compared to the placebo group. After 4 month of treatment with pantogam, the severity of functional disturbances was reduced by 4 out of 6 WFIRS-P domains: Family, School and learning, Child's self-concept and Risky activities. Pantogam improved the measures of sustained attention (accuracy and speed) in the Toulouse-Piéron test. The drug used in mean daily dose 30 mg/kg during 4 month had a favorable safety profile which did not differ from that of placebo.

  16. A randomised placebo-controlled trial to differentiate the acute cognitive and mood effects of chlorogenic acid from decaffeinated coffee.

    Directory of Open Access Journals (Sweden)

    David A Camfield

    Full Text Available In the current study, sixty healthy older adults aged 50 years or older, and who were light to moderate coffee drinkers, were administered 6g of a decaffeinated green coffee blend (NESCAFÉ Green Blend coffee; GB or 540mg pure chlorogenic acids (CGA or placebo in a double-blind acute cross-over design, with cognitive and mood assessments pre-dose, 40-mins and 120-mins post-dose. The primary outcome measure was accuracy in Rapid Visual Information Processing (RVIP. Secondary cognitive outcome measures included RVIP reaction time as well as Inspection time (IT, Jensen Box decision/reaction times, serial subtraction and N-Back working memory. Secondary mood measures included Bond-Lader and caffeine Research visual analogue scales (VAS. No significant treatment effects were found for the primary outcome measure, although significant effects were found amongst secondary measures. Overall, CGA in isolation was not found to significantly improve cognitive function relative to placebo whereas the GB was found to improve sustained attention as measured by the N-Back task in comparison to placebo overall (t=2.45,p=.05, as well as decision time on a 2-choice reaction time task (Jensen box in comparison to placebo at 40 minutes post-dose (t=2.45,p=.05. Similarly, GB was found to improve alertness on both the Bond-Lader at 120 minutes relative to CGA (t=2.86, p=0.02 and the caffeine Research VAS relative to CGA (t=3.09, p=0.009 and placebo (t=2.75,p=0.02 at 120 minutes post-dose. Both the GB and CGA were also found to significantly improve symptoms of headache at 120 minutes relative to placebo (t=2.51,p=0.03 and t=2.43,p=.04 respectively, whilst there was a trend towards a reduction in jitteriness with GB and CGA in comparison to placebo at 40 minutes post-dose (t=2.24,p=0.06 and t=2.20,p=0.06 respectively. These findings suggest that the improvements in mood observed with GB, but not the improvements in cognitive function, are likely to some extent to be

  17. Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study; a multicenter randomized placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Onland Wes

    2011-11-01

    Full Text Available Abstract Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD. However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR: NTR2768

  18. Effect of collagen hydrolysate in articular pain: a 6-month randomized, double-blind, placebo controlled study.

    Science.gov (United States)

    Bruyère, O; Zegels, B; Leonori, L; Rabenda, V; Janssen, A; Bourges, C; Reginster, J-Y

    2012-06-01

    Evaluation of the efficacy and safety of a food supplement made of collagen hydrolysate 1200 mg/day versus placebo during 6 months, in subjects with joint pain at the lower or upper limbs or at the lumbar spine. Comparative double-blind randomized multicenter study in parallel groups. 200 patients of both genders of at least 50 years old with joint pain assessed as ≥30 mm on a visual analogical scale (VAS). Collagen hydrolysate 1200 mg/day or placebo during 6 months. Comparison of the percentage of clinical responder between the active collagen hydrolysate group and the placebo group after 6 months of study. A responder subject was defined as a subject experiencing a clinically significant improvement (i.e. by 20% or more) in the most painful joint using the VAS score. All analyses were performed using an intent-to-treat procedure. At 6 months, the proportion of clinical responders to the treatment, according to VAS scores, was significantly higher in the collagen hydrolysate (CH) group 51.6%, compared to the placebo group 36.5% (pvs. 39.6%, p=0.53). No significant difference in terms of security and tolerability was observed between the two groups. This study suggests that collagen hydrolysate 1200 mg/day could increase the number of clinical responders (i.e. improvement of at least 20% on the VAS) compared to placebo. More studies are needed to confirm the clinical interest of this food supplement. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Sun, Qianqian; Wang, Bin; Li, Yingsha; Sun, Fang; Li, Peng; Xia, Weijie; Zhou, Xunmei; Li, Qiang; Wang, Xiaojing; Chen, Jing; Zeng, Xiangru; Zhao, Zhigang; He, Hongbo; Liu, Daoyan; Zhu, Zhiming

    2016-03-01

    Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function. © 2016 American Heart Association, Inc.

  20. Testosterone and estrogen impact social evaluations and vicarious emotions: A double-blind placebo-controlled study.

    Science.gov (United States)

    Olsson, Andreas; Kopsida, Eleni; Sorjonen, Kimmo; Savic, Ivanka

    2016-06-01

    The abilities to "read" other peoples' intentions and emotions, and to learn from their experiences, are critical to survival. Previous studies have highlighted the role of sex hormones, notably testosterone and estrogen, in these processes. Yet it is unclear how these hormones affect social cognition and emotion using acute hormonal administration. In the present double-blind placebo-controlled study, we administered an acute exogenous dose of testosterone or estrogen to healthy female and male volunteers, respectively, with the aim of investigating the effects of these steroids on social-cognitive and emotional processes. Following hormonal and placebo treatment, participants made (a) facial dominance judgments, (b) mental state inferences (Reading the Mind in the Eyes Test), and (c) learned aversive associations through watching others' emotional responses (observational fear learning [OFL]). Our results showed that testosterone administration to females enhanced ratings of facial dominance but diminished their accuracy in inferring mental states. In men, estrogen administration resulted in an increase in emotional (vicarious) reactivity when watching a distressed other during the OFL task. Taken together, these results suggest that sex hormones affect social-cognitive and emotional functions at several levels, linking our results to neuropsychiatric disorders in which these functions are impaired. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  1. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Udani Jay K

    2010-08-01

    Full Text Available Abstract Background Arabinogalactan from Larch tree (Larix spp. bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g at the screening visit (V1-Day 0 and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2. They were monitored the following day (V3-Day 31, as well as 21 days (V4-Day 51 and 42 days (V5-Day 72 after vaccination. Responses by the adaptive immune system (antigen specific were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F and salivary IgA levels. Responses by the innate immune system (non-specific were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F at both Day 51 (p = 0.006 and p = 0.002 and at Day 72 (p = 0.008 and p = 0.041. These same subtypes (18C and 23F also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001 and at Day 72 (p = 0.012 and p = 0.003. Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There

  2. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers.

    Science.gov (United States)

    Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

    2010-08-26

    Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no effect from the vaccine or

  3. Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study.

    Science.gov (United States)

    O'Donnell, Colin P; Allott, Kelly A; Murphy, Brendan P; Yuen, Hok Pan; Proffitt, Tina-Marie; Papas, Alicia; Moral, Jennifer; Pham, Tee; O'Regan, Michaela K; Phassouliotis, Christina; Simpson, Raelene; McGorry, Patrick D

    2016-12-01

    Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder. 121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009. Patients taking low-dose antipsychotic medication were randomly assigned to receive once-daily taurine 4 g or placebo for 12 weeks. The coprimary outcomes were change in symptomatology (measured by the Brief Psychiatric Rating Scale [BPRS] total score) and change in cognition (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery composite score) at 12 weeks. Secondary outcomes included tolerability and safety and additional clinical and functioning measures. 86 participants (n = 47 taurine; n = 39 placebo) were included in the final analysis. Taurine significantly improved symptomatology measured by the BPRS total score (95% CI, 1.8-8.5; P = .004) and psychotic subscale (95% CI, 0.1-1.5; P = .026) compared to placebo. Additionally, improvements were observed in the Calgary Depression Scale for Schizophrenia (95% CI, 0.1-3.0; P = .047) and Global Assessment of Functioning (95% CI, 0.3-8.8; P = .04) scores. There was no group difference in composite cognitive score (95% CI, -1.7 to 1.0; P = .582). A significant group difference was found on one safety and tolerability item (psychic item 2, asthenia/lassitude/increased fatigability) of the Udvalg for Kliniske Undersogelser, with the taurine group showing a

  4. Effect of caffeine on maximal oxygen uptake in wheelchair rugby players: A randomized, placebo-controlled, double-blind study

    Directory of Open Access Journals (Sweden)

    Iva Klimešová

    2017-03-01

    Full Text Available Background: The positive effects of caffeine supplementation on strength-power and endurance performance in healthy athletes have been demonstrated in many studies. A possible mechanism for its ergogenic effect relates to its influence on the central nervous system. Post-traumatic complications in cervical spinal cord injury affect almost all body systems including the nervous system. For this reason, we expect that caffeine will have a different effect of performance in the group of athletes with spinal cord injuries. Objective: To examine the effects of caffeine supplementation on maximal aerobic power in elite wheelchair rugby players. Methods: Seven elite male wheelchair rugby players with complete cervical-level SCI (C4-Th1 were recruited (mean age: 28 ± 5.42 years; mean body mass index: 26 ± 2.84 kg/m2. The effect of caffeine was assessed by an incremental arm ergometer test until volitional exhaustion. The maximal oxygen uptake (VO2max/kg, maximum power (W max/kg, peak heart rate (HR peak, and intensity of perceived exertion (RPE were measured. Participants performed the test twice with a two-week washout period. One hour before each exercise test subjects ingested a capsule of placebo or caffeine (3 mg per kg of body weight. The tests were applied in a double-blind, randomized, repeated-measures, and cross-over design. Wheelchair rugby players were chosen because of the expected high homogeneity of participants - in terms of the type and degree of disability, gender, and age of the players. Results: The monitored parameters were not significantly influenced by caffeine intervention as compared to placebo: VO2max/kg (p = .40, W max/kg (p = .34, HR peak (p = .50 and RPE (p = .50. Conclusions: The current findings suggest that a caffeine dose of 3 mg/kg body mass does not improve oxygen uptake and maximal power in elite wheelchair rugby players.

  5. The effect of intra-articular injection of ultracain in the temporomandibular joint in patients with preauricular pain - A randomized prospective double-blind placebo-controlled crossover study

    NARCIS (Netherlands)

    Tjakkes, Geerten-Has E.; TenVergert, Elisabeth M.; de Bont, Lambert G. M.; Stegenga, Boudewijn

    2007-01-01

    Objectives: To evaluate the distinguishing ability of intraarticular anesthesia from placebo in orofacial pain patients with pain located in the temporomandibular joint (TMJ) region, aiming at a validation of intra-articular anesthesia injection as a diagnostic test of pain in the TMJ region.

  6. Prevention of head louse infestation: a randomised, double-blind, cross-over study of a novel concept product, 1% 1,2-octanediol spray versus placebo.

    Science.gov (United States)

    Burgess, Ian F; Brunton, Elizabeth R; French, Rebecca; Burgess, Nazma A; Lee, Peter N

    2014-05-30

    To determine whether regular use of a spray containing 1,2-octanediol 1%, which has been shown to inhibit survival of head lice, is able to work as a preventive against establishment of new infestations. Randomised, double-blind, cross-over, community study in Cambridgeshire, UK. 63 male and female schoolchildren aged 4-16 years judged to have a high risk of recurrent infestation. Only the youngest member of a household attending school participated. Participants were treated to eliminate lice, randomised between 1% octanediol or placebo sprays for 6 weeks then crossed-over to the other spray for 6 weeks. Parents applied the sprays at least twice weekly or more frequently if the hair was washed. Investigators monitored weekly for infestation and replenished supplies of spray. The primary endpoint was the time taken until the first infestation event occurred. The secondary measure was safety of the product in regular use. Intention-to-treat analysis found a total of 32 confirmed infestations in 20 participants, with 9 of them infested while using both products. In these nine participants the time to first infestation showed a significant advantage to 1% octanediol (p=0.0129). Per-protocol analysis showed only trends because the population included was not large enough to demonstrate significance. There were no serious adverse events and only two adverse events possibly related to treatment, one was a case of transient erythema and another of a rash that resolved after 5 days. Routine use of 1% octanediol spray provided a significant level of protection from infestation. It was concluded that this product is effective if applied regularly and thoroughly. ISRCTN09524995. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Re: A Randomized Double-Blind Placebo-Controlled Phase 2 Dose-Ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Ozan Bozkurt

    2015-09-01

    Full Text Available Botulinum toxin is a neurotoxin inhibiting the release of acetylcholine and is used in various fields of medicine. Recently, it has been proposed as an alternative minimally invasive treatment modality for patients unresponsive to oral therapies. The present study is the largest prospective, randomized and placebo-controlled study investigating the efficacy and safety of different onabotulinumtoxinA (BTX-A doses in men with moderate to severe lower urinary tract symptoms (LUTS associated with benign prostatic hyperplasia (BPH. 100 U, 200 U and 300 U BTX-A doses via transperineal or transrectal route were injected within the transition zone of each lateral lobe. 69.7% of patients (115 of 380 completed the 72-week study. The authors reported significant improvement for all treatment arms including placebo from weeks 2 through 72 including the primary time point of week 12. There were no statistically significant differences between BTX-A groups and placebo in terms of treatment efficacy described as International Prostate Symptom Score (IPSS reduction, improvement of peak urinary flow rate (Qmax and post-void residual volume (PVR and prostate volume reduction at any time point throughout the study. Only in a subgroup of patients, including previous alpha-blocker users, 200 U BTX-A worked better than placebo in terms of IPSS reduction. Adverse event rates were similar between all treatment arms. The unexpected pronounced placebo response in the present study raises question marks in minds regarding the use of BTX-A as an alternative treatment option. These conflicting results suggest that intraprostatic BTX-A injection is still experimental and further trials are required.

  8. Exposure–response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development

    Science.gov (United States)

    Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

    2015-01-01

    No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs. PMID:26392753

  9. Exposure-response model for sibutramine and placebo: suggestion for application to long-term weight-control drug development.

    Science.gov (United States)

    Han, Seunghoon; Jeon, Sangil; Hong, Taegon; Lee, Jongtae; Bae, Soo Hyeon; Park, Wan-su; Park, Gab-jin; Youn, Sunil; Jang, Doo Yeon; Kim, Kyung-Soo; Yim, Dong-Seok

    2015-01-01

    No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure-response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure-response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects' sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure-response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs.

  10. Consistent and significant improvement of nighttime voiding frequency (nocturia) with silodosin in men with LUTS suggestive of BPH: pooled analysis of three randomized, placebo-controlled, double-blind phase III studies.

    Science.gov (United States)

    Eisenhardt, Andreas; Schneider, Tim; Cruz, Francisco; Oelke, Matthias

    2014-10-01

    Nocturia is prevalent and bothersome in men with lower urinary tract symptoms suggestive of BPH (LUTS/BPH). α-Adrenoceptor antagonists without subtype selectivity have inconsistently shown significant effects on nocturia in these patients. We explored the effects of the α1A-adrenoceptor subtype-selective antagonist silodosin on nocturia by analyzing three placebo-controlled registration studies. Responses to question 7 of the IPSS questionnaire were analyzed for the entire study population and patients with ≥ 2 voids/night at baseline. Improvement/worsening rates for nocturia were calculated for once-daily silodosin 8 mg and placebo. Silodosin effects on the mean number of nocturnal voids were compared with placebo, and the number of patients in whom nocturia was reduced to silodosin or placebo; 1,266 men (85 %) had ≥ 2 voids/night at baseline. Compared to placebo, more men treated with silodosin reported about nocturia improvement (53.4 vs. 42.8 %, p Silodosin significantly reduced nocturia within each study and pooled cohort compared to placebo (p silodosin and placebo had reductions of ≥ 1 voids/night, respectively (p = 0.0003), and significantly more patients with silodosin had nocturia episodes at study end compared to placebo (29.3 vs. 19.0 %; p = 0.0002). Although a weak impact on nocturia is already known from α-adrenoceptor antagonists without subtype selectivity, the individual placebo-controlled studies and the pooled data analysis showed that the α1A-adrenoceptor subtype-selective antagonist silodosin consistently and significantly improves nocturia in men with LUTS/BPH.

  11. Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: A randomized, double-blind crossover trial

    OpenAIRE

    Bogaard, Bas; Draijer, Richard; Westerhof, Berend; Meiracker, Anton; Montfrans, Gert; Born, B.J.H.

    2010-01-01

    textabstractFlavanol-rich cocoa products have been reported to lower blood pressure. It has been suggested that theobromine is partially responsible for this effect. We tested whether consumption of flavanol-rich cocoa drinks with natural or added theobromine could lower peripheral and central blood pressure. In a double-blind, placebo-controlled 3-period crossover trial we assigned 42 healthy individuals (age 62±4.5 years; 32 men) with office blood pressure of 130 to 159 mm Hg/85 to 99 mm Hg...

  12. The Effect of EMLA Cream on Patient-Controlled Analgesia with Remifentanil in ESWL Procedure: A Placebo-Controlled Randomized Study.

    Science.gov (United States)

    Acar, Arzu; Erhan, Elvan; Nuri Deniz, M; Ugur, Gulden

    2013-01-01

    To alleviate stinging pain in the skin entry area and visceral discomfort in patients who are undergoing ESWL. This study was designed to investigate the effectiveness of the EMLA cream in combination with remifentanil patient-controlled analgesia (PCA) in patients undergoing ESWL treatment. Sixty patients were divided into two double-blind randomized groups. Those in the first group were administered 3-5mm of EMLA 5% cream on a marked area; the second group received, as a placebo, a cream with no analgesic effect in the same amount. All patients were administered a remifentanil bolus with a PCA device. Arterial blood pressure, oxygen saturation, and respiratory rate were recorded throughout the procedure; postoperative side effects, agitation, and respiratory depression were measured after. Visual Analogue Scale (VAS) scores were taken preoperatively, perioperatively, directly postoperatively, and 60 minutes subsequent to finishing the procedure. There were no statistically significant differences in the frequency of PCA demands and delivered boluses or among perioperative VAS. No significant side effects were noted. Patient satisfaction was recorded high in both groups. EMLA cream offered no advantage over the placebo cream in patients undergoing ESWL with remifentanil PCA.

  13. Phytoestrogens/insoluble fibers and colonic estrogen receptor β: Randomized, double-blind, placebo-controlled study

    Science.gov (United States)

    Principi, Mariabeatrice; Di Leo, Alfredo; Pricci, Maria; Scavo, Maria Principia; Guido, Raffaella; Tanzi, Sabina; Piscitelli, Domenico; Pisani, Antonio; Ierardi, Enzo; Comelli, Maria Cristina; Barone, Michele

    2013-01-01

    AIM: To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS: A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS: No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION: The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study. PMID:23885143

  14. Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicenter, randomized, double-blind, placebo-controlled, parallel-group studies

    DEFF Research Database (Denmark)

    Kajdasz, Daniel K; Iyengar, Smriti; Desaiah, Durisala

    2007-01-01

    peripheral neuropathic pain (DPNP). METHODS: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as >or=30...

  15. Intravenous lysine clonixinate for the acute treatment of severe migraine attacks: a double-blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Krymchantowski, Abouch Valenty; Silva, Marcus Tulius T

    2003-09-01

    Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in the treatment of migraine. However, few commercially available NSAIDs can be administered IV. Lysine clonixinate (LC), an NSAID derived from nicotinic acid, has been proved effective in various algesic syndromes (eg, renal colic, muscular pain, nerve compression, odontalgia). The oral formulation of LC has been shown to be effective in the treatment of migraine of moderate severity. The aim of this study was to assess the efficacy and tolerability of the IV formulation of LC in the treatment of severe migraine. This double-blind, randomized, placebo-controlled, prospective study enrolled patients with severe migraine (without aura) as defined by the criteria of the International Headache Society. When patients presented to a neurology hospital with an outpatient headache unit (Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil) with a severe migraine attack that had lasted <4 hours, they were randomized to 1 of 2 groups (IV placebo [25 mL of 0.9% saline] or IV LC [21 mL of 0.9% saline plus 4 mL of LC 200 mg]). Headache intensity and adverse effects (AEs) were assessed before (0 minute) and 30, 60, and 90 minutes after study drug administration. Rescue medication was available 2 hours after study drug administration, and its use was compared between groups. Thirty-two patients (23 women, 9 men; mean [SD] age, 32 [2] years; range, 18-58 years) entered the study. Twenty-nine patients (21 women, 8 men; mean [SD] age, 32 [2] years; range, 18-56 years) completed the study. Three patients (all in the placebo group) did not complete the study (1 patient was unable to rate the pain severity after drug administration and 2 patients refused IV drug administration). Among study completers, 17 patients received LC and 12 placebo. At 30 minutes, 1 patient (8.3%) in the placebo group and 5 patients (29.4%) in the LC group were pain free; the between-group difference was not

  16. Intravenous lysine clonixinate for the acute treatment of severe migraine attacks: a double-blind, randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Abouch Valenty Krymchantowski, MD, PhD

    2003-09-01

    Full Text Available Background: Several nonsteroidal anti-inflammatory drugs (NSAIDs have been shown to be effective in the treatment of migraine. However, few commercially available NSAIDs can be administered IV. Lysine clonixinate (LC, an NSAID derived from nicotinic acid, has been proved effective in various algesic syndromes (eg, renal colic, muscular pain, nerve compression, odontalgia. The oral formulation of LC has been shown to be effective in the treatment of migraine of moderate severity. Objective: The aim of this study was to assess the efficacy and tolerability of the IV formulation of LC in the treatment of severe migraine. Methods: This double-blind, randomized, placebo-controlled, prospective study enrolled patients with severe migraine (without aura as defined by the criteria of the International Headache Society. When patients presented to a neurology hospital with an outpatient headache unit (Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil with a severe migraine attack that had lasted <4 hours, they were randomized to 1 of 2 groups (IV placebo [25 mL of 0.9% saline] or IV LC [21 mL of 0.9% saline plus 4 mL of LC 200 mg]. Headache intensity and adverse effects (AEs were assessed before (0 minute and 30, 60, and 90 minutes after study drug administration. Rescue medication was available 2 hours after study drug administration, and its use was compared between groups. Results: Thirty-two patients (23 women, 9 men; mean [SD] age, 32 [2] years; range, 18–58 years entered the study. Twenty-nine patients (21 women, 8 men; mean [SD] age, 32 [2] years; range, 18–56 years completed the study. Three patients (all in the placebo group did not complete the study (1 patient was unable to rate the pain severity after drug administration and 2 patients refused IV drug administration. Among study completers, 17 patients received LC and 12 placebo. At 30 minutes, 1 patient (8.3% in the placebo group and 5 patients (29.4% in the LC group were

  17. Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram.

    Science.gov (United States)

    Lavretsky, Helen; Siddarth, Prabha; Irwin, Michael R

    2010-02-01

    This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blinded trial. Forty family caregivers (43-91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient's cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28. The groups were stratified by the diagnosis of major and minor depression. Most outcomes favored escitalopram over placebo. The severity of depression improved, and the remission rate was greater with the drug compared with placebo. Measures of anxiety, resilience, burden, and distress improved on escitalopram compared with placebo. Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample.

  18. A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

    Science.gov (United States)

    Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

    2017-12-01

    The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

  19. Oral lysine clonixinate in the acute treatment of migraine: a double-blind placebo-controlled study Clonixinato de lisina oral para o tratamento agudo da migrânea: estudo duplo-cego e placebo-controlado

    Directory of Open Access Journals (Sweden)

    Abouch V. Krymchantowski

    2001-03-01

    Full Text Available Several oral nonsteroidal anti-inflammatory drugs (NSAIDs are effective to treat migraine attacks. Lysine clonixinate (LC is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks.Alguns antinflamatórios não esteroidais (AINEs são eficazes para o tratamento de crises de migrânea. O clonixinato de lisina (CL é um AINE derivado do ácido nicotínico comprovadamente eficaz no tratamento de várias síndromes dolorosas como a cólica renal e a dor muscular. O objetivo deste estudo duplo-cego placebo-controlado foi avaliar a eficácia do CL oral comparado ao placebo no tratamento agudo da migrânea. Sessenta e quatro pacientes com o diagnóstico de migrânea, de acordo com os critérios da Sociedade Internacional de Cefaléia (IHS, foram estudados prospectivamente. Os pacientes receberam CL ou placebo quando a cefaléia atingiu a intensidade moderada ou severa em 6 crises consecutivas. Para as crises moderadas, o CL foi superior ao placebo em 1, 2 e 4

  20. Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

    Science.gov (United States)

    Robb, Adelaide; Bose, Anjana

    2013-01-01

    Abstract Objective The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods Adolescents (12–17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10–20 mg versus placebo could enroll in a 16–24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were

  1. Duloxetine in the treatment of binge eating disorder with depressive disorders: a placebo-controlled trial.

    Science.gov (United States)

    Guerdjikova, Anna I; McElroy, Susan L; Winstanley, Erin L; Nelson, Eric B; Mori, Nicole; McCoy, Jessica; Keck, Paul E; Hudson, James I

    2012-03-01

    This study evaluated duloxetine in the treatment of binge eating disorder (BED) with comorbid current depressive disorders. In this 12-week, double-blind, placebo-controlled trial, 40 patients with Diagnostic and Statistical Manual of Mental Disorders-IV-TR BED and a comorbid current depressive disorder received duloxetine (N = 20) or placebo (N = 20). The primary outcome measure was weekly binge eating day frequency. In the primary analysis, duloxetine (mean 78.7 mg/day) was superior to placebo in reducing weekly frequency of binge eating days (p = .04), binge eating episodes (p = .02), weight (p = .04), and Clinical Global Impression-Severity of Illness ratings for binge eating (p = .02) and depressive disorders (p = .01). Changes in body mass index and measures of eating pathology, depression, and anxiety did not differ between the two groups. Duloxetine may be effective for reducing binge eating, weight, and global severity of illness in BED with a comorbid current depressive disorder, but this finding needs confirmation in larger, placebo-controlled trials. Copyright © 2011 Wiley Periodicals, Inc.

  2. Evaluation of Isosorbide Mononitrate for Preinduction of Cervical Ripening: A Randomized Placebo-Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ramya Krishnamurthy

    2015-06-01

    Full Text Available To evaluate the safety and efficacy of Isosorbide mononitrate (IMN as a cervical ripening agent prior to induction of labour in term pregnant women.A randomized placebo-controlled study was conducted on 100 term singleton pregnancies planned for induction of labour. The participants were randomly assigned to two groups. One group received 40 mg IMN and the other group received 40mg of placebo kept vaginally. The main outcome of this study was to evaluate the efficacy of IMN in cervical ripening based on the change in modified Bishop score and the effect on time duration between the drug insertion and delivery. Safety of isosorbide mononitrate was assessed by measuring variables related to maternal and neonatal outcomes.Baseline demographic characteristics were similar in both groups. The mean change in modified Bishop score after 2 doses of 40mg IMN was insignificant when compared to placebo. Though IMN shortened the time duration between the drug insertion to delivery when compared to placebo, it was statistically insignificant. The need for oxytocin and 2(nd ripening agent was less in IMN group when compared to placebo group but statistically this also proved to be insignificant. It was noted that there was an increase in caesarean deliveries in IMN than in placebo group. IMN did not cause any significant change in maternal hemodynamics and adverse side effects. Though NICU admission and stay was less in IMN than in placebo group, it was statistically insignificant.Though IMN did not cause any maternal and neonatal adverse effects, it was found to be inefficient in comparison to placebo as a cervical ripening agent.

  3. Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stéphanie J.E. Becker

    2014-09-01

     Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial. 

  4. Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and wrinkling: A randomized, double-blind, and placebo-controlled study.

    Science.gov (United States)

    Kim, Do Un; Chung, Hee Chul; Kim, Changhee; Hwang, Jae-Kwan

    2017-12-01

    Photoaging is a severe skin damage that occurs as a result of exposure to external elements, primarily ultraviolet (UV) irradiation. Chronically, UV-irradiated skin exhibits the signs of sunburn and hyperpigmentation with the destruction of connective tissues. Previously, Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed antiphotoaging activities in vitro and in vivo. The aim of this study was to investigate the clinical efficacy of B. pandurata intake on skin hydration, gloss, wrinkling, and elasticity. A double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of B. pandurata ethanol extract (BPE) containing 8% of panduratin A on human skin hydration, gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to receive tablets containing either BPE or placebo for 12 weeks. The test group had significantly increased skin hydration and gloss and decreased wrinkling compared to the placebo group at 12 weeks. There was no significant difference in skin elasticity between the two groups; however, the increment rate in the test group was higher than that in the placebo group at 12 weeks. None of the subjects developed adverse symptoms during the study period. These results suggest that BPE can be used as a nutraceutical or nutricosmetic material for improving human skin hydration, gloss, and wrinkling. © 2017 Wiley Periodicals, Inc.

  5. Audiovisual distraction for pain relief in paediatric inpatients: A crossover study.

    Science.gov (United States)

    Oliveira, N C A C; Santos, J L F; Linhares, M B M

    2017-01-01

    Pain is a stressful experience that can have a negative impact on child development. The aim of this crossover study was to examine the efficacy of audiovisual distraction for acute pain relief in paediatric inpatients. The sample comprised 40 inpatients (6-11 years) who underwent painful puncture procedures. The participants were randomized into two groups, and all children received the intervention and served as their own controls. Stress and pain-catastrophizing assessments were initially performed using the Child Stress Scale and Pain Catastrophizing Scale for Children, with the aim of controlling these variables. The pain assessment was performed using a Visual Analog Scale and the Faces Pain Scale-Revised after the painful procedures. Group 1 received audiovisual distraction before and during the puncture procedure, which was performed again without intervention on another day. The procedure was reversed in Group 2. Audiovisual distraction used animated short films. A 2 × 2 × 2 analysis of variance for 2 × 2 crossover study was performed, with a 5% level of statistical significance. The two groups had similar baseline measures of stress and pain catastrophizing. A significant difference was found between periods with and without distraction in both groups, in which scores on both pain scales were lower during distraction compared with no intervention. The sequence of exposure to the distraction intervention in both groups and first versus second painful procedure during which the distraction was performed also significantly influenced the efficacy of the distraction intervention. Audiovisual distraction effectively reduced the intensity of pain perception in paediatric inpatients. The crossover study design provides a better understanding of the power effects of distraction for acute pain management. Audiovisual distraction was a powerful and effective non-pharmacological intervention for pain relief in paediatric inpatients. The effects were

  6. Preventing ICU Subsyndromal Delirium Conversion to Delirium with Low Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study

    Science.gov (United States)

    Al-Qadheeb, Nada S.; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel; Roberts, Russel; Ruthazer, Robin; Devlin, John W

    2016-01-01

    Objective To compare the efficacy and safety of scheduled low-dose, haloperidol vs. placebo for the prevention of delirium [Intensive Care Delirium Screening Checklist (ICDSC) ≥ 4)] administered to critically ill adults with subsyndromal delirium (ICDSC = 1-3). Design Randomized, double-blind, placebo-controlled trial. Setting Three 10-bed ICUs (2 medical; 1 surgical) at an academic medical center in the U.S. Patients Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery or requiring deep sedation. Interventions Patients were randomly assigned to receive intravenous haloperidol 1 mg or placebo every six hours until either delirium (ICDSC ≥ 4 with psychiatric confirmation), therapy ≥ 10 days or ICU discharge occurred. Measurements and Main Results Baseline characteristics were similar between the haloperidol (n=34) and placebo (n=34) groups. A similar number of patients given haloperidol [12/34 (35%)] and placebo [8/34 (23%)] patients developed delirium (p=0.29). Haloperidol use reduced the hours per study day spent agitated (SAS ≥ 5) (p=0.008), but did not influence the proportion of 12-hour ICU shifts patients’ spent alive without coma (SAS ≤ 2) or delirium (p=0.36), the time to first delirium occurrence (p=0.22) nor delirium duration (p=0.26). Days of mechanical ventilation (p=0.80), ICU mortality (p=0.55) and ICU patient disposition (p=0.22) were similar in the two groups. The proportion of patients who developed QTc-interval prolongation (p=0.16), extrapyramidal symptoms (p=0.31), excessive sedation (p=0.31) or new-onset hypotension (p=1.0) that resulted in study drug discontinuation was comparable between the two groups. Conclusions Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium. PMID:26540397

  7. Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study.

    Science.gov (United States)

    Al-Qadheeb, Nada S; Skrobik, Yoanna; Schumaker, Greg; Pacheco, Manuel N; Roberts, Russel J; Ruthazer, Robin R; Devlin, John W

    2016-03-01

    To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3). Randomized, double-blind, placebo-controlled trial. Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States. Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation. Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge. Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ≤ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups. Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults

  8. Double blind, placebo-controlled trial of Tranexamic acid on recent internal hemorrhoid bleeding

    Directory of Open Access Journals (Sweden)

    Abdul A. Rani

    2002-12-01

    Full Text Available Double blind randomized placebo controlled trial was conducted to evaluate the efficacy of Tranexamic acid in 54 patients with recent hemorrhoid bleeding. Age, gender, body weight, height, grade of hemorrhoid, time of onset of recent bleeding were comparable between two groups. Analysis of haemostatic effect or stop bleeding as an immediate outcome of this study revealed that in the grade 2 patients, 23/23 (100% of tranexamic group and 18/23(78.26% of placebo group the bleeding stop. After 3 days of observation, there was statistically significant different for the rate of stop bleeding as well as at the end of observation. Bleeding stop earlier in the Tranexamic group with median 4 days (3-5 days, compare to placebo, median 11(9.55-12.45. Analysis of recurrent bleeding as an outcome of this study revealed that in the placebo group 9/18(50% of grade 2 patients and all grade 3 (100%patients suffered from recurrent bleeding. Since the days 4, both group have significant different time for recurrent bleeding and at the end of observation, cumulative probability of free of bleeding between two groups significantly different. Median still stop bleeding in the placebo group was 36 days, and the tranexamic group never reaches the median until the end of observation. Conclusion: tranexamic acid was an effective drug to stop recent hemorrhoid bleeding and prevent further recurrent bleeding, significantly better than placebo. (Med J Indones 2002;11: 215-21Keywords: Tranexamic acid, hemorrhoid bleeding, haemostatic effect, recurrent bleeding.

  9. Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

    Science.gov (United States)

    Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

    2009-07-01

    To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

  10. Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study.

    Science.gov (United States)

    Rowe, K S; Rowe, K J

    1994-11-01

    To establish whether there is an association between the ingestion of synthetic food colorings and behavioral change in children referred for assessment of "hyperactivity." From approximately 800 children referred to the Royal Children's Hospital (Melbourne) for assessment of suspected hyperactivity, 200 were included in a 6-week open trial of a diet free of synthetic food coloring. The parents of 150 children reported behavioral improvement with the diet, and deterioration on the introduction of foods noted to contain synthetic coloring. A 30-item behavioral rating inventory was devised from an examination of the clinical histories of 50 suspected reactors. Thirty-four other children (23 suspected reactors, 11 uncertain reactors) and 20 control subjects, aged 2 to 14 years, were studied. A 21-day, double-blind, placebo-controlled, repeated-measures study used each child as his or her own control. Placebo, or one of six dose levels of tartrazine (1, 2, 5, 10, 20, 50 mg), was administered randomly each morning, and behavioral ratings were recorded by parents at the end of each 24 hours. The study identified 24 children as clear reactors (19 of 23 "suspected reactors," 3 of 11 "uncertain reactors," and 2 of 20 "control subjects"). They were irritable and restless and had sleep disturbance. Significant reactions were observed at all six dose levels. A dose response effect was obtained. With a dose increase greater than 10 mg, the duration of effect was prolonged. Behavioral changes in irritability, restlessness, and sleep disturbance are associated with the ingestion of tartrazine in some children. A dose response effect was observed.

  11. Effect of low-level laser therapy in the treatment of cochlear tinnitus: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Dehkordi, Mahboobeh Adami; Einolghozati, Sasan; Ghasemi, Seyyed Mohsen; Abolbashari, Samaneh; Meshkat, Mojtaba; Behzad, Hadi

    2015-01-01

    Many treatments for chronic tinnitus have been attempted, but the condition remains difficult to cure, especially in the case of cochlear tinnitus. We conducted a prospective, double-blind, placebo-controlled study to assess the effect of low-dose laser therapy on chronic cochlear tinnitus. Our study population was made up of 66 patients-33 who received active laser treatment (case group) and 33 who received inactive dummy treatment (control group). Patients in the laser group received 5 mV with a wavelength of 650 nm for 20 minutes a day, 5 days a week, for 4 weeks. The controls followed the same schedule, but they were "treated" with an inactive device. The degree of tinnitus was evaluated before and after treatment in each group in three ways: (1) the Tinnitus Severity Index (TSI), (2) a subjective 10-point self-assessment scale for tinnitus loudness, and (3) the Tinnitus Evaluation Test (TET). At study's end, we found no statistically significant differences between the case and control groups in the number of patients who experienced a reduction in TSI values (p = 0.589) or a reduction in subjective self-assessment scores (p = 0.475). Nor did we find any significant reductions in the loudness (p = 0.665) and frequency (p = 0.396) of tinnitus as determined by the TET. We conclude that 5-mV laser therapy with a wavelength of 650 nm is no better than placebo for improving hearing thresholds overall or for treating tinnitus with regard to age, sex, environmental noise level, and the duration of tinnitus.

  12. Physical dependence increases the relative reinforcing effects of caffeine versus placebo.

    Science.gov (United States)

    Garrett, B E; Griffiths, R R

    1998-10-01

    Using a within-subject cross-over design, this study examined the role of physical dependence in caffeine reinforcement by experimentally manipulating physical dependence. Each subject was exposed to two chronic drug phases (300 mg/70 kg/day caffeine and placebo) for 9-12 days, with order of phases counterbalanced across subjects. On 2 separate days immediately following each of the chronic drug exposures, subjects received acute doses of either caffeine (300 mg/70 kg) or placebo in counterbalanced order. The reinforcing effects of these drugs were then determined by using a multiple-choice procedure in which subjects made a series of discrete choices between receiving varying amounts of money or receiving the drug again, and a choice between the two drugs. To ensure that subjects completed the form carefully, following exposure to both of the acute drug administrations, one of the subject's previous choices from the multiple-choice form was randomly selected and the consequence of that choice was implemented. When subjects were maintained on chronic caffeine, they were willing to forfeit significantly more money and showed significant increases in typical withdrawal symptoms (e.g. fatigue, mood disturbance) after receiving placebo as compared to the other three conditions. When subjects were maintained on chronic caffeine, they also chose to receive caffeine over placebo twice as often than when they were maintained on chronic placebo. These findings provide the strongest evidence to date indicating that caffeine physical dependence increases the relative reinforcing effects of caffeine versus placebo.

  13. Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Tania Cursino de Menezes Couceiro

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

  14. Acute Effect of Topical Menthol on Chronic Pain in Slaughterhouse Workers with Carpal Tunnel Syndrome: Triple-Blind, Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Emil Sundstrup

    2014-01-01

    Full Text Available Topical menthol gels are classified “topical analgesics” and are claimed to relieve minor aches and pains of the musculoskeletal system. In this study we investigate the acute effect of topical menthol on carpal tunnel syndrome (CTS. We screened 645 slaughterhouse workers and recruited 10 participants with CTS and chronic pain of the arm/hand who were randomly distributed into two groups to receive topical menthol (Biofreeze or placebo (gel with a menthol scent during the working day and 48 hours later the other treatment (crossover design. Participants rated arm/hand pain intensity during the last hour of work (scale 0–10 immediately before 1, 2, and 3 hours after application. Furthermore, global rating of change (GROC in arm/hand pain was assessed 3 hours after application. Compared with placebo, pain intensity and GROC improved more following application of topical menthol (P=0.026 and P=0.044, resp.. Pain intensity of the arm/hand decreased by −1.2 (CI 95%: −1.7 to −0.6 following topical menthol compared with placebo, corresponding to a moderate effect size of 0.63. In conclusion, topical menthol acutely reduces pain intensity during the working day in slaughterhouse workers with CTS and should be considered as an effective nonsystemic alternative to regular analgesics in the workplace management of chronic and neuropathic pain.

  15. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Harris, Deborah L; Weston, Philip J; Signal, Matthew; Chase, J Geoffrey; Harding, Jane E

    2013-12-21

    Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35-42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2·6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0·57, 95% CI 0·33-0·98; p=0·04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0·9 mmol/L. No other adverse events took place. Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel

  16. Effect of preoperative medications on the efficacy of inferior alveolar nerve block in patients with irreversible pulpitis: A placebo-controlled clinical study.

    Science.gov (United States)

    Jena, Amit; Shashirekha, Govind

    2013-03-01

    The purpose of this prospective, randomized, double-blind, placebo-controlled study was to compare the effect of the administration of preoperative ibuprofen, ketorolac, combination of etodolac with paracetamol and combination of aceclofenac with paracetamol versus placebo for the potential increased effectiveness of the inferior alveolar nerve block [IANB] anesthesia. A total of 100 endodontic emergency patients in moderate to severe pain diagnosed with irreversible pulpitis of a mandibular posterior tooth randomly received, in a double-blind manner, either a drug or placebo 30 minutes before the administration of a conventional IANB. Cold testing was done before administration of anesthesia to determine level of pain using Heft-Parker Visual Analogue Scale (VAS) score. Success was defined as no pain or pain (VAS) on access or initial instrumentation. Overall success was 54% for all the groups. Success was highest (70%) for the ketorolac group, 55% for both ibuprofen group and combination of aceclofenac with paracetamol group, 50% for combination of etodolac with paracetamol group, and 40% for the placebo group. Under the conditions of this study, the use of preoperative medication did improve the anesthetic efficacy of IANB for the treatment of teeth diagnosed with irreversible pulpitis but not significantly.

  17. Effect of sodium nitrite on renal function, sodium and water excretion and brachial and central blood pressure in healthy subjects. A dose-response study

    DEFF Research Database (Denmark)

    Rosenbaek, Jeppe Bakkestroem; Therwani, Safa Al; Jensen, Janni Majgaard

    2017-01-01

    Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2 on hemodynamics, sodium excretion and GFR. In a single-blinded, placebo-controlled, cross-over study, we infused placebo (0.9% NaCl) or 0.58, ....... The lack of increase in cGMP accompanying the increase in NO2(-), suggests a direct effect of nitrite or nitrate on the renal tubules and vascular bed with little or no systemic conversion to NO.......Sodium nitrite (NaNO2) is converted to nitric oxide (NO) in vivo and has vasodilatory and natriuretic effects. Our aim was to examine the effects of NaNO2 on hemodynamics, sodium excretion and GFR. In a single-blinded, placebo-controlled, cross-over study, we infused placebo (0.9% NaCl) or 0.58, 1.......74, or 3.48 μmol NaNO2/kg/hour for two hours in twelve healthy subjects, after four days standard diet. Subjects were supine and water-loaded. We measured brachial and central blood pressure (BP), plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin (P-AVP), and plasma nitrite...

  18. Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Wieringen, S. van; Jansen, T.; Smits, M.G.; Nagtegaal, J.E.; Coenen, A.M.L.

    2001-01-01

    Objective: To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the

  19. Homeopathy for Depression - DEP-HOM: study protocol for a randomized, partially double-blind, placebo controlled, four armed study

    Science.gov (United States)

    2011-01-01

    Background Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. Methods/Design A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 × 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. Discussion For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the

  20. Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: a prospective, randomized, placebo-controlled study.

    Science.gov (United States)

    Luoto, Raakel; Laitinen, Kirsi; Nermes, Merja; Isolauri, Erika

    2012-06-01

    The breast milk bioactive substances such as adiponectin, have a presumably long-term impact upon the health and well-being of a child. To determine the impact of probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration. Altogether 256 pregnant women were randomized into three study groups: dietary intervention with probiotics (diet/probiotics) or with placebo (diet/placebo) and a control group (control/placebo). The intervention group received dietary counseling provided by a nutritionist, the main focus being the amount and the type of dietary fat. The probiotics used were Lactobacillus rhamnosus GG and Bifidobacterium lactis in combination. Dietary intake was evaluated by food records at every trimester of pregnancy. Breast milk samples were collected after birth (colostrum) for adiponectin concentration analysis (n=181). The dietary intervention increased the colostrum adiponectin concentration (ng/mL, geometric mean [95% CI]), the difference being significant when comparing to the control group; 12.7 [10.6-29.7] vs. 10.2 [9.9-13.2], P=0.024. Maternal weight gain during pregnancy (kg) correlated inversely with colostrum adiponectin concentration; β (SE)=-1.7 (0.1), P=0.020, and gestational diabetes mellitus was associated with the likelihood of adiponectin concentration falling into the lowest quartile; OR 2.36, 95% CI 1.1-3.2, P=0.028. In showing that the colostrum adiponectin concentration is markedly dependent on maternal diet and nutritional status during pregnancy, and considering that colostrum adiponectin has potential effects on metabolism, nutrition, and immune function in the neonates, the results of this study underscore the importance of the metabolic homeostasis of the mother for the child's initial nutritional environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. The effect of different dosage regimens of tranexamic acid on blood loss in bimaxillary osteotomy: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Apipan, B; Rummasak, D; Narainthonsaenee, T

    2018-05-01

    The purpose of this study was to compare the effects of three dosage regimens of intravenous tranexamic acid and normal saline placebo on blood loss and the requirement for transfusion during bimaxillary osteotomy. A prospective, randomized, double-blind, placebo-controlled study was performed. Eighty patients scheduled for elective bimaxillary osteotomy were divided into four groups: a placebo group and three groups receiving a single dose of tranexamic acid 10, 15, or 20mg/kg body weight after the induction of anaesthesia. Demographic data, the anaesthetic time, the operative time, and the experience of the surgical team were similar in the four groups. Patients receiving placebo had increased blood loss compared to those receiving tranexamic acid. No significant difference in blood loss was found among those who received 10, 15, or 20mg/kg body weight of tranexamic acid. There was no significant difference in transfusion requirement, amount of 24-h postoperative vacuum drainage, length of hospital stay, or complications among the four groups. Prophylactic tranexamic acid decreased bleeding during bimaxillary osteotomy. Of the three dosages of tranexamic acid studied, the most efficacious and cost-effective dose to reduce bleeding was 10mg/kg body weight. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Efficacy of polyglucosamine for weight loss?confirmed in a randomized double-blind, placebo-controlled clinical investigation

    OpenAIRE

    Pokhis, Karina; Bitterlich, Norman; Cornelli, Umberto; Cassano, Giuseppina

    2015-01-01

    Background The purpose of this clinical study was to ascertain whether low molecular weight chitosan polyglucosamine is able to produce significantly better weight loss than placebo. Method 115 participants were included in the study. We used a two-center randomized, double blind, placebo-controlled design. The participants followed a standard treatment (ST), which included the combination of a low-calorie diet achieved through creating a daily calorie deficit (500 cal) and an increased daily...

  3. [Placebo effect in Parkinson's disease].

    Science.gov (United States)

    Miwa, Hideto

    2007-02-01

    "Placebo" is Latin for "I shall please". The placebo effect has been widely documented by randomized placebo-controlled drug studies. One of the best examples of placebo effectiveness is that have been shown in clinical trials of anti-parkinsonian drugs. The placebo effect is observable not only in drug trials but also with deep brain stimulation. Recent advances in research on the placebo effect in Parkinson's disease (PD) have suggested that motor symptoms of PD can be essentially improved by placebo. A recent study using positron emission tomography (PET) with raclopride demonstrated that release of endogeneous dopamine in the dorsal striatum occurs in placebo-responsive patients with PD. This suggests that placebo-induced expectation of clinical improvement may activate endogenous dopamine in the striatum, and that placebo effectiveness is thus achieved by endogenous dopamine supplementation. Indeed, decreased neuronal activities in the subthalamic nucleus (STN), that were recorded during surgery to implant deep brain stimulation electrodes, correlated well with placebo-induced clinical improvement in patients with PD. Although the detailed pathophysiological mechanism underlying the placebo effects remains uncertain, theoretically, the placebo effect has generally been explained by two different mechanisms: one is conditioning theory (pavlovian conditioning), and the other is cognitive theory (expectation of clinical improvement). Although both mechanisms may contribute to placebo effects, the placebo effect in PD may be attributed more to cognitive mechanisms such as expectation of improvement, because the placebo effect can be obtained in de novo PD patients. There have been accumulating findings that suggest a functional relationship between dopamine and the expectation of clinical improvement (reward). Further basic studies are required to clarify the complex link between dopamine and the reward system, but such findings will contribute to a better

  4. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

    DEFF Research Database (Denmark)

    Demant, Dyveke T; Lund, Karen; Vollert, Jan

    2014-01-01

    In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo...... patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment....... The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined...

  5. Placebo - More hatred than love

    Directory of Open Access Journals (Sweden)

    Hong-Liang Zhang

    2011-01-01

    Full Text Available A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs, which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

  6. Placebo - More hatred than love.

    Science.gov (United States)

    Zhang, Hong-Liang

    2011-01-01

    A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs), which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

  7. A Randomized Double-Blind Placebo-Controlled Study of Omalizumab Combined with Oral Immunotherapy for the Treatment of Cow’s Milk Allergy

    Science.gov (United States)

    Wood, Robert A.; Kim, Jennifer S.; Lindblad, Robert; Nadeau, Kari; Henning, Alice K.; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A.

    2017-01-01

    Background Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy as benefits usually diminish when treatment is discontinued. Objective We sought to examine whether the addition of omalizumab to milk OIT (MOIT) reduces treatment-related reactions and/or improves outcomes. Methods This was a double-blind placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label MOIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22–40 weeks, followed by daily maintenance dosing through month-28. At month-28, omalizumab was discontinued and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with re-challenge at month-32 to assess sustained unresponsiveness (SU). Results Fifty-seven subjects (7–32 years) were randomized, with no significant baseline differences in age, milk-specific IgE, skin tests, or OFCs. At month-28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10 gram “desensitization” OFC (p=0.18). At month-32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (p=0.42). Adverse reactions were markedly reduced during OIT escalation in omalizumab subjects for percent doses/subject provoking symptoms (2.1% versus 16.1%; p=0.0005), dose-related reactions requiring treatment (0.0% versus 3.8%, p=0.0008), and doses required to achieve maintenance (198 versus 225; p=0.008). Conclusions In this first randomized double-blinded placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety, but not in outcomes of efficacy (desensitization and SU). Trial Registration OIT and XolairR (Omalizumab) in Cow’s Milk Allergy, NCT01157117, http://clinicaltrials.gov/show/NCT01157117

  8. The effects of Lactobacillus reuteri probiotics combined with azithromycin on peri-implantitis: A randomized placebo-controlled study.

    Science.gov (United States)

    Tada, Hiroaki; Masaki, Chihiro; Tsuka, Shintaro; Mukaibo, Taro; Kondo, Yusuke; Hosokawa, Ryuji

    2018-01-01

    The aim of this randomized placebo-controlled clinical study was to investigate the effects of a probiotic tablet containing Lactobacillus reuteri in peri-implantitis patients. Subjects comprised 30 patients with mild to moderate peri-implantitis. A baseline clinical examination and microbiological assessment were conducted, followed by an antibiotics treatment (azithromycin, 500mg, once a day for 3 days). Subjects were divided into probiotic and placebo groups. The clinical examination and bacterial sampling were performed 0, 4, 12 and 24 weeks after the intake of probiotics. The clinical examination included probing pocket depth (PPD), bleeding on probing (BOP), the modified plaque index (mPI), and modified bleeding index (mBI). The number of bacteria was assessed using the PCR-invader method. The Wilcoxon rank-sum test and Wilcoxon signed-rank test with Bonferroni corrections were used for data analyses. Although the number of bacteria decreased after the administration of azithromycin in both groups, they increased again thereafter. No significant difference was observed in bacterial numbers between the two groups. Although PPD in the probiotics group was significantly lower at 4 and 24 weeks than at 0 weeks (pprobiotics group than in the placebo group (pprobiotics prevent inflammation by affecting host responses rather than improving microbial flora in peri-implant sulci in peri-implantitis patients. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  9. A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain.

    Science.gov (United States)

    Henderson, D C; Fan, X; Copeland, P M; Borba, C P; Daley, T B; Nguyen, D D; Zhang, H; Hayden, D; Freudenreich, O; Cather, C; Evins, A E; Goff, D C

    2007-02-01

    This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted.

  10. Studies on Methanol Crossover in Liquid-Feed Direct Methanol Pem Fuel Cells

    Science.gov (United States)

    Narayanan, S. R.

    1995-01-01

    The performance of liquid feed direct methanol fuel cells using various types of Nafion membranes as the solid polymer electrolyte have been studied. The rate of fuel crossover and electrical performance has been measured for cells with Nafion membranes of various thicknesses and equivalent weights. The crossover rate is found to decrease with increasing thickness and applied current. The dependence of crossover rate on current density can be understood in terms of a simple linear diffusion model which suggests that the crossover rate can be influenced by the electrode structure in addition to the membrane. The studies suggest that Nafion EW 1500 is a very promising alternate to Nafion EW 1100 for direct methanol fuel cells.

  11. N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

    Science.gov (United States)

    Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

    2013-01-01

    Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

  12. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.

    Science.gov (United States)

    Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

    2015-08-01

    To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40,000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. RhEPO 40,000 IU fortnightly did not change the course of ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Use of Placebo in Supplementation Studies—Vitamin D Research Illustrates an Ethical Quandary

    Directory of Open Access Journals (Sweden)

    Leigh A. Frame

    2018-03-01

    Full Text Available History has shown that without explicit and enforced guidelines, even well-intentioned researchers can fail to adequately examine the ethical pros and cons of study design choices. One area in which consensus does not yet exist is the use of placebo groups in vitamin supplementation studies. As a prime example, we focus on vitamin D research. We aim to provide an overview of the ethical issues in placebo-controlled studies and guide future discussion about the ethical use of placebo groups. Research in the field of vitamin D shows variation in how placebo groups are used. We outline four types of control groups in use: active-control, placebo-control with restrictions on supplementation, placebo-control without supplementation restrictions, and placebo-control with rescue repletion therapy. The first two types highlight discrete ethical issues: active-control trials limit the ability to detect a difference; placebo-control trials that restrict supplementation potentially place subjects at risk of undue harm. The final two, placebo-control without supplementation restrictions or with rescue repletion therapy, offer potential solutions to these ethical challenges. Building on this, guidelines should be established and enforced on the use of placebo in supplementation studies. Furthermore, the field of vitamin D research has the potential to set an example worthy of emulation.

  14. The Effect of Aromatherapy Abdominal Massage on Alleviating Menstrual Pain in Nursing Students: A Prospective Randomized Cross-Over Study

    Directory of Open Access Journals (Sweden)

    Tyseer M. F. Marzouk

    2013-01-01

    Full Text Available Dysmenorrhea is a common cause of sickness absenteeism from both classes and work. This study investigated the effect of aromatherapy massage on a group of nursing students who are suffering of primary dysmenorrhea. A randomized blind clinical trial of crossover design was used. In the first treatment phase, group 1 ( received aromatherapy abdominal massage once daily for seven days prior to menstruation using the essential oils (cinnamon, clove, rose, and lavender in a base of almond oil. Group 2 ( received the same intervention but with placebo oil (almond oil. In the second treatment phase, the two groups switched to alternate regimen. Level and duration of pain and the amount of menstrual bleeding were evaluated at the baseline and after each treatment phase. During both treatment phases, the level and duration of menstrual pain and the amount of menstrual bleeding were significantly lower in the aromatherapy group than in the placebo group. These results suggests that aromatherapy is effective in alleviating menstrual pain, its duration and excessive menstrual bleeding. Aromatherapy can be provided as a nonpharmacological pain relief measure and as a part of nursing care given to girls suffering of dysmenorrhea, or excessive menstrual bleeding.

  15. Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial.

    Science.gov (United States)

    Babl, Franz E; Mackay, Mark T; Borland, Meredith L; Herd, David W; Kochar, Amit; Hort, Jason; Rao, Arjun; Cheek, John A; Furyk, Jeremy; Barrow, Lisa; George, Shane; Zhang, Michael; Gardiner, Kaya; Lee, Katherine J; Davidson, Andrew; Berkowitz, Robert; Sullivan, Frank; Porrello, Emily; Dalziel, Kim Marie; Anderson, Vicki; Oakley, Ed; Hopper, Sandy; Williams, Fiona; Wilson, Catherine; Williams, Amanda; Dalziel, Stuart R

    2017-02-13

    Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial. We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio

  16. Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Kanzaki, Noriyuki; Ono, Yoshiko; Shibata, Hiroshi; Moritani, Toshio

    2015-01-01

    The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren-Lawrence (K-L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, Pknee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions.

  17. Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

    Science.gov (United States)

    Peluso, Rosario; Caso, Francesco; Costa, Luisa; Sorbo, Dario; Carraturo, Nello; Di Minno, Matteo Nicola Dario; Carraturo, Federica; Oriente, Alfonso; Balestrieri, Umberto; Minicucci, Annamaria; Del Puente, Antonio; Scarpa, Raffaele

    2016-01-01

    To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

  18. Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode

    NARCIS (Netherlands)

    Storosum, Jitschak G.; Wohlfarth, Tamar; Gispen-de Wied, Christine C.; Linszen, Don H.; Gersons, Berthold P. R.; van Zwieten, Barbara J.; van den Brink, Wim

    2005-01-01

    Objective: The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic/depressive episode. If so, this would be a strong ethical argument

  19. Equimolar mixture of nitroux oxyde and oxygen during post-operative physiotherapy in patients with cerebral palsy: A randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Delafontaine, A; Presedo, A; Mohamed, D; Lopes, D; Wood, C; Alberti, C

    2017-11-01

    The administration of an equimolar mixture of nitrous oxide and oxygen (N2O) is recommended during painful procedures. However, the evaluation of its use during physiotherapy after surgery has not been reported, although pain may hamper physiotherapy efficiency. This study investigated whether the use of N2O improves the efficacy of post-operative physiotherapy after multilevel surgery in patients with cerebral palsy. It was a randomized 1:1, double-blind, placebo-controlled study. All patients had post-operative physiotherapy starting the day after surgery. Patients received either N2O or placebo gas during the rehabilitation sessions. All patients had post-operative pain management protocol, including pain medication as needed for acute pain. The primary objective was to reach angles of knee flexion of 110° combined with hip extension of 10°, with the patient lying prone, within six or less physiotherapy sessions. Secondary evaluation criteria were the number of sessions required to reach the targeted angles, the session-related pain intensity and the analgesics consumption for managing post-operative pain. Sixty-four patients were enrolled. Targeted angles were achieved more often in the N2O group (23 of 32, 72%, vs. Placebo: 13/ of 32, 41%; p = 0.01). The administration of N2O during post-operative physiotherapy can help to achieve more quickly an improved range of motion, and, although not significant in our study, to alleviate the need for pain medication. Further studies evaluating the administration of N2O in various settings are warranted. During this randomized placebo-controlled double-blind study, children receiving nitrous oxide and oxygen (N2O) achieved more often the targeted range of motion during physiotherapy sessions after multilevel surgery. Compared to placebo, nitrous oxide and oxygen (N2O) enabled a better management of acute pain related to physiotherapy procedures. © 2017 European Pain Federation - EFIC®.

  20. Crossover integral equation theory for the liquid structure study

    International Nuclear Information System (INIS)

    Lai, S.K.; Chen, H.C.

    1994-08-01

    The main purpose of this work is to report on a calculation that describes the role of the long-range bridge function [H. Iyetomi and S. Ichimaru, Phys. Rev. A 25, 2434 (1982)] as applied to the study of structure of simple liquid metals. It was found here that this bridge function accounts pretty well for the major part of long-range interactions but is physically inadequate for describing the short-range part of liquid structure. To improve on the theory we have drawn attention to the crossover integral equation method which, in essence, amounts to adding to the above bridge function a short-range correction of bridge diagrams. The suggested crossover procedure has been tested for the case of liquid metal Cs. Remarkably good agreement with experiment was obtained confirming our conjecture that the crossover integral equation approach as stressed in this work is potentially an appropriate theory for an accurate study of liquid structure possibly for the supercooled liquid regime. (author). 21 refs, 3 figs