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Sample records for placebo-controlled parallel-group dual

  1. A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms

    OpenAIRE

    Feldman Samantha; Alvarez Patricia; Schwartz Howard I; Kalman Douglas S; Pezzullo John C; Krieger Diane R

    2009-01-01

    Abstract Background This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. Methods Sixty-one adults were enrolled (age 36.5 ± 12.6 years; height 165.1 ± 9.2 cm; weight 75.4 ± 17.3 kg) and randomized to either Digest...

  2. A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms

    Directory of Open Access Journals (Sweden)

    Feldman Samantha

    2009-11-01

    Full Text Available Abstract Background This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence but no gastrointestinal (GI diagnoses to explain the symptoms. Methods Sixty-one adults were enrolled (age 36.5 ± 12.6 years; height 165.1 ± 9.2 cm; weight 75.4 ± 17.3 kg and randomized to either Digestive Advantage™ Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086: n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA bloating and gas subscores over four weeks of product use. Results Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046 and the GSRS total score (p = 0.048, with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061. A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. Conclusion In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. Trial Registration ClinicalTrials.gov Identifier: NCT00881322

  3. A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms

    Science.gov (United States)

    2009-01-01

    Background This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. Methods Sixty-one adults were enrolled (age 36.5 ± 12.6 years; height 165.1 ± 9.2 cm; weight 75.4 ± 17.3 kg) and randomized to either Digestive Advantage™ Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use. Results Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. Conclusion In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. Trial Registration ClinicalTrials.gov Identifier: NCT00881322 PMID:19922649

  4. A prospective, randomized, double-blind, placebo-controlled parallel-group dual site trial to evaluate the effects of a Bacillus coagulans-based product on functional intestinal gas symptoms.

    Science.gov (United States)

    Kalman, Douglas S; Schwartz, Howard I; Alvarez, Patricia; Feldman, Samantha; Pezzullo, John C; Krieger, Diane R

    2009-11-18

    This randomized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-prandial intestinal gas-related symptoms (abdominal pain, distention, flatulence) but no gastrointestinal (GI) diagnoses to explain the symptoms. Sixty-one adults were enrolled (age 36.5 +/- 12.6 years; height 165.1 +/- 9.2 cm; weight 75.4 +/- 17.3 kg) and randomized to either Digestive Advantage Gas Defense Formula - (GanedenBC30 Bacillus coagulans GBI-30, 6086): n = 30; or Placebo: n = 31. Study subjects were evaluated every two weeks over a four-week period using validated questionnaires and standard biochemical safety testing. Outcome criteria of interest included change from baseline in Gastrointestinal Symptom Rating Scale (GSRS) abdominal pain, abdominal distention, flatus, and the Severity of Dyspepsia Assessment (SODA) bloating and gas subscores over four weeks of product use. Measured against the placebo, subjects in the probiotic group achieved significant improvements in GSRS abdominal pain subscore (p = 0.046) and the GSRS total score (p = 0.048), with a strong trend for improvement on the GSRS abdominal distension subscore (p = 0.061). A strong placebo effect was evident which could explain the lack of statistical significant differences between the groups for many of the efficacy variables. In conclusion, the Bacillus coagulans-based product was effective in improving the quality of life and reducing gastrointestinal symptoms in adults with post prandial intestinal gas-related symptoms and no GI diagnoses. ClinicalTrials.gov Identifier: NCT00881322.

  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. The efficacy of Femal in women with premenstrual syndrome: a randomised, double-blind, parallel-group, placebo-controlled, multicentre study

    DEFF Research Database (Denmark)

    Gerhardsen, G.; Hansen, A.V.; Killi, M.

    2008-01-01

    Introduction: A double-blind, placebo-controlled, randomised, parallel-group, multicentre study was conducted to evaluate the effect of a pollen-based herbal medicinal product, Femal (R) (Sea-Band Ltd, Leicestershire, UK), on premenstrual sleep disturbances (PSD) in women with premenstrual syndrome...... as the main symptom cluster makes this herbal medicinal product a promising addition to the therapeutic arsenal for women with PMS Udgivelsesdato: 2008/6...

  7. Mandibular advancement appliance for obstructive sleep apnoea: results of a randomised placebo controlled trial using parallel group design

    DEFF Research Database (Denmark)

    Petri, N.; Svanholt, P.; Solow, B.

    2008-01-01

    The aim of this trial was to evaluate the efficacy of a mandibular advancement appliance (MAA) for obstructive sleep apnoea (OSA). Ninety-three patients with OSA and a mean apnoea-hypopnoea index (AHI) of 34.7 were centrally randomised into three, parallel groups: (a) MAA; (b) mandibular non......). Eighty-one patients (87%) completed the trial. The MAA group achieved mean AHI and Epworth scores significantly lower (P group and the no-intervention group. No significant differences were found between the MNA group and the no-intervention group. The MAA group had...

  8. A double blind parallel group placebo controlled comparison of sedative and mnesic effects of etifoxine and lorazepam in healthy subjects [corrected].

    Science.gov (United States)

    Micallef, J; Soubrouillard, C; Guet, F; Le Guern, M E; Alquier, C; Bruguerolle, B; Blin, O

    2001-06-01

    This paper describes the psychomotor and mnesic effects of single oral doses of etifoxine (50 and 100 mg) and lorazepam (2 mg) in healthy subjects. Forty-eight healthy subjects were included in this randomized double blind, placebo controlled parallel group study [corrected]. The effects of drugs were assessed by using a battery of subjective and objective tests that explored mood and vigilance (Visual Analog Scale), attention (Barrage test), psychomotor performance (Choice Reaction Time) and memory (digit span, immediate and delayed free recall of a word list). Whereas vigilance, psychomotor performance and free recall were significantly impaired by lorazepam, neither dosage of etifoxine (50 and 100 mg) produced such effects. These results suggest that 50 and 100 mg single dose of etifoxine do not induce amnesia and sedation as compared to lorazepam.

  9. 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...

  10. Pharmacokinetics, safety, and tolerability of varenicline in healthy adolescent smokers: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study.

    Science.gov (United States)

    Faessel, Helene; Ravva, Patanjali; Williams, Kathryn

    2009-01-01

    Varenicline is approved as an aid to smoking cessation in adults aged > or =18 years. The goal of this study was to characterize the multiple-dose pharmacokinetics, safety, and tolerability of varenicline in adolescent smokers. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled healthy 12- to 16-year-old smokers (> or =3 cigarettes daily) into high-body-weight (>55 kg) and low-body-weight (daily. The apparent renal clearance (CL/F) and volume of distribution (V/F) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling. The high-body-weight group consisted of 35 subjects (65.7% male; 77.1% white; mean age, 15.2 years). The low-body-weight group consisted of 37 subjects (37.8% male; 48.6% white; mean age, 14.3 years). The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d. The CL/F for a 70-kg adolescent was 10.4 L/h, comparable to that in a 70-kg adult. The estimated varenicline V/F was decreased in individuals of small body size, thus predicting a varenicline C(max) approximately 30% greater in low-body-weight subjects than in high-body-weight subjects. In high-body-weight subjects, steady-state varenicline exposure, as represented by the AUC(0-24), was 197.0 ng . h/mL for varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID, consistent with values reported previously in adult smokers at the equivalent doses. In low-body-weight subjects, varenicline exposure was 126.3 ng . h/mL for varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily, values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID, respectively. Among high-body-weight subjects, adverse events (AEs) were reported by 57.1% of subjects in both the high- and low-dose varenicline groups and by 14.3% of subjects in the placebo group; among low-body-weight subjects, AEs

  11. Effects of policosanol on borderline to mildly elevated serum total cholesterol levels: a prospective, double-blind, placebo-controlled, parallel-group, comparative study

    Directory of Open Access Journals (Sweden)

    Gladys Castaño, PhD

    2003-09-01

    Full Text Available Background: Hypercholesterolemia is a major risk factor for coronary heart disease. Clinical studies have shown that lowering elevated serum cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C, is beneficial for patients with borderline to mildly elevated serum total cholesterol (TC levels (5.0–6.0 mmol/L. Policosanol is a cholesterol-lowering drug made from purified sugar cane wax. The therapeutic range of policosanol is 5 to 20 mg/d. Objective: This study investigated the efficacy and tolerability of policosanol 5 mg/d in patients with borderline to mildly elevated serum TC levels. Methods: This 14-week, single-center, prospective, double-blind, placebo-controlled, parallel-group, comparative study was conducted in men and women aged 25 to 75 years with a serum TC level ≥4.8 to <6.0 mmol/L. After a 6-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular a cholesterol-lowering diet, patients were randomly assigned to receive policosanol 5-mg tablets or placebo tablets once daily with the evening meal for 8 weeks, and the diet was continued throughout the study. Lipid profile variables, safety indicators, adverse events (AEs, and compliance with study medications were assessed. Results: One hundred patients (71 women, 29 men; mean [SD] age, 52 [10] years entered the study after the dietary run-in period. After 8 weeks of treatment, the mean (SD serum LDL-C level decreased significantly in the policosanol group (P<0.001 vs baseline and placebo from 3.57 (0.30 mmol/L to 2.86 (0.41 mmol/L (change, −19.9%. Significantly more patients in the policosanol group (42 patients [84%] achieved a ≥15% decrease in serum LDL-C than in the placebo group (2 patients [4%] (P<0.001. Also in the policosanol group, the mean (SD serum TC level decreased significantly, from 5.20 (0.22 mmol/L to 4.56 (0.44 mmol/L (P<0.001 vs baseline and placebo (change, −12.3%; the mean (SD triglyceride (TG

  12. Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebo-controlled, parallel-group, multiple-dose study.

    Science.gov (United States)

    Boulton, Craig; Meiser, Karin; David, Olivier J; Schmouder, Robert

    2012-12-01

    Fingolimod, a first-in-class oral sphingosine 1-phosphate receptor (S1PR) modulator, is approved in many countries for relapsing-remitting multiple sclerosis, at a once-daily 0.5-mg dose. A reduction in peripheral lymphocyte count is an expected consequence of the fingolimod mechanism of S1PR modulation. The authors investigated if this pharmacodynamic effect impacts humoral and cellular immunogenicity. In this double-blind, parallel-group, 4-week study, 72 healthy volunteers were randomized to steady state, fingolimod 0.5 mg, 1.25 mg, or to placebo. The authors compared T-cell dependent and independent responses to the neoantigens, keyhole limpet hemocyanin (KLH), and pneumococcal polysaccharides vaccine (PPV-23), respectively, and additionally recall antigen response (tetanus toxoid [TT]) and delayed-type hypersensitivity (DTH) to KLH, TT, and Candida albicans. Fingolimod caused mild to moderate decreases in anti-KLH and anti-PPV-23 IgG and IgM levels versus placebo. Responder rates were identical between placebo and 0.5-mg groups for anti-KLH IgG (both > 90%) and comparable for anti-PPV-23 IgG (55% and 41%, respectively). Fingolimod did not affect anti-TT immunogenicity, and DTH response did not differ between placebo and fingolimod 0.5-mg groups. Expectedly, lymphocyte count reduced substantially in the fingolimod groups versus placebo but reversed by study end. Fingolimod was well tolerated, and the observed safety profile was consistent with previous reports.

  13. Isoflavones, calcium, vitamin D and inulin improve quality of life, sexual function, body composition and metabolic parameters in menopausal women: result from a prospective, randomized, placebo-controlled, parallel-group study.

    Science.gov (United States)

    Vitale, Salvatore Giovanni; Caruso, Salvatore; Rapisarda, Agnese Maria Chiara; Cianci, Stefano; Cianci, Antonio

    2018-03-01

    Menopause results in metabolic changes that contribute to increase risk of cardiovascular diseases: increase in low density lipoprotein (LDL) and triglycerides and decrease in high density lipoprotein (HDL), weight gain are associated with a correspondent increase in incidence of hypertension and diabetes. The aim of this study was to evaluate the effect of a preparation of isoflavones, calcium vitamin D and inulin in menopausal women. We performed a prospective, randomized, placebo-controlled, parallel-group study. A total of 50 patients were randomized to receive either oral preparations of isoflavones (40 mg), calcium (500 mg) vitamin D (300 UI) and inulin (3 g) or placebo (control group). Pre- and post-treatment assessment of quality of life and sexual function were performed through Menopause-Specific Quality of Life Questionnaire (MENQOL) and Female Sexual Function Index (FSFI); evaluations of anthropometric indicators, body composition through bioelectrical impedance analyser, lumbar spine and proximal femur T-score and lipid profile were performed. After 12 months, a significant reduction in MENQOL vasomotor, physical and sexual domain scores ( p 0.05) were found in the same group. According to our data analysis, isoflavones, calcium, vitamin D and inulin may exert favourable effects on menopausal symptoms and signs.

  14. A Herbal Medicine, Gongjindan, in Subjects with Chronic Dizziness (GOODNESS Study: Study Protocol for a Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Clinical Trial for Effectiveness, Safety, and Cost-Effectiveness

    Directory of Open Access Journals (Sweden)

    Seungwon Shin

    2017-01-01

    Full Text Available This study protocol aims to explore the effectiveness, safety, and cost-effectiveness of a herbal medication, Gongjindan (GJD, in patients with chronic dizziness. This will be a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, clinical trial. Seventy-eight patients diagnosed with Meniere’s disease, psychogenic dizziness, or dizziness of unknown cause will be randomized and allocated to either a GJD or a placebo group in a 1 : 1 ratio. Participants will be orally given 3.75 g GJD or placebo in pill form once a day for 56 days. The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will be as follows: severity (mean vertigo scale and visual analogue scale and frequency of dizziness, balance function (Berg Balance Scale, fatigue (Fatigue Severity Scale and deficiency pattern/syndrome (qi blood yin yang-deficiency questionnaire levels, and depression (Korean version of Beck’s Depression Inventory and anxiety (State-Trait Anxiety Inventory levels. To assess safety, adverse events, including laboratory test results, will be monitored. Further, the incremental cost-effectiveness ratio will be calculated based on quality-adjusted life years (from the EuroQoL five dimensions’ questionnaire and medical expenses. Data will be statistically analyzed at a significance level of 0.05 (two-sided. This trial is registered with ClinicalTrials.gov NCT03219515, in July 2017.

  15. Efficacy of treatment of insomnia in migraineurs with eszopiclone (Lunesta®) and its effect on total sleep time, headache frequency, and daytime functioning: A randomized, double-blind, placebo-controlled, parallel-group, pilot study.

    Science.gov (United States)

    Spierings, Egilius L H; McAllister, Peter J; Bilchik, Tanya R

    2015-04-01

    A review on headache and insomnia revealed that insomnia is a risk factor for increased headache frequency and headache intensity in migraineurs. The authors designed a randomized, double blind, placebo-controlled, parallel-group, pilot study in which migraineurs who also had insomnia were enrolled, to test this observation. In the study, the authors treated 79 subjects with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia for 6 weeks with 3 mg eszopiclone (Lunesta(®)) or placebo at bedtime. The treatment was preceded by a 2-week baseline period and followed by a 2-week run-out period. Of the 79 subjects treated, 75 were evaluable, 35 in the eszopiclone group, and 40 in the placebo group. At baseline, the groups were comparable except for sleep latency. Of the three remaining sleep variables, total sleep time, nighttime awakenings, and sleep quality, the number of nighttime awakenings during the 6-week treatment period was significantly lower in the eszopiclone group than in the placebo group (P = 0.03). Of the three daytime variables, alertness, fatigue, and functioning, this was also the case for fatigue (P = 005). The headache variables, frequency, duration, and intensity, did not show a difference from placebo during the 6-week treatment period. The study did not meet primary endpoint, that is, the difference in total sleep time during the 6-week treatment period between eszopiclone and placebo was less than 40 minutes. Therefore, it failed to answer the question as to whether insomnia is, indeed, a risk factor for increased headache frequency and headache intensity in migraineurs.

  16. Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

    Science.gov (United States)

    Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-07-01

    A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd.

  17. A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.

    Science.gov (United States)

    Amalraj, Augustine; Varma, Karthik; Jacob, Joby; Divya, Chandradhara; Kunnumakkara, Ajaikumar B; Stohs, Sidney J; Gopi, Sreeraj

    2017-10-01

    Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.

  18. Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol).

    Science.gov (United States)

    Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Poulsen, Henrik Enghusen; Nielsen, René Ernst; Berk, Michael; Dean, Olivia May; Mohebbi, Mohammadreza; Nielsen, Connie Thuroee

    2018-04-05

    Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress. In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences. Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.

  19. A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients.

    Science.gov (United States)

    Fukagawa, Masafumi; Yokoyama, Keitaro; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Kuramoto, Takuto; Odani, Motoi; Akizawa, Tadao

    2017-10-01

    Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT. In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2.5 and 15 mg at 4-week intervals for 12 weeks. A total of 155 SHPT patients with serum intact parathyroid hormone (iPTH) levels ≥300 pg/mL were assigned to receive etelcalcetide (n = 78) or placebo (n = 77). The primary endpoint was the proportion of patients with decreased serum iPTH to the target range proposed by the Japanese Society for Dialysis Therapy (60-240 pg/mL). The major secondary endpoint was the proportion of patients with ≥30% reductions in serum iPTH from baseline. The proportion of patients meeting the primary endpoint was significantly higher for etelcalcetide (59.0%) versus placebo (1.3%). Similarly, the proportion of patients meeting the major secondary endpoint was significantly higher for etelcalcetide (76.9%) versus placebo (5.2%). Serum albumin-corrected calcium, phosphorus and intact fibroblast growth factor-23 levels were decreased in the etelcalcetide group. Nausea, vomiting and symptomatic hypocalcaemia were mild with etelcalcetide. Serious adverse events related to etelcalcetide were not observed. This study demonstrated the efficacy and safety of etelcalcetide. As the only available intravenous calcium-sensing receptor agonist, etelcalcetide is likely to provide a new treatment option for SHPT in haemodialysis patients. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

  20. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain.

    Science.gov (United States)

    Lee, Jae Hyup; Lee, Chong-Suh

    2013-11-01

    Chronic low back pain is a common condition that is often difficult to treat. The combination of tramadol hydrochloride and acetaminophen in an extended-release formulation has been shown to provide rapid and long-lasting analgesic effects resulting from the synergistic activity of these 2 active ingredients. The goal of this study was to evaluate the efficacy and safety of extended-release tramadol hydrochloride 75-mg/acetaminophen 650-mg fixed-dose combination tablets (TA-ER) for the treatment of chronic low back pain. This Phase III, double-blind, placebo-controlled, parallel-group study enrolled 245 patients with moderate to severe (≥4 cm on a 10-cm visual analog scale) chronic (≥3 months') low back pain insufficiently controlled by previous NSAIDs or cyclooxygenase-2-selective inhibitors and randomly assigned them to receive 4 weeks of either TA-ER or placebo. The primary efficacy end point was the percentage of patients with a pain intensity change rate ≥30% from baseline to final evaluation. Secondary end points included quality of life (Korean Short Form-36), functionality (Korean Oswestry Disability Index), and adverse events. The percentage of patients with a pain intensity change rate ≥30% was significantly higher (P Pain relief success rate from baseline was significantly higher with TA-ER versus placebo at days 8 and 15 but not at the final visit. Patients in the TA-ER group had significant improvements versus placebo in role-physical, general health, and reported health transition domains of the Korean Short Form-36 and significantly higher functional improvements in the personal care section of the Korean Oswestry Disability Index. Patient assessment of overall pain control as "very good" was also significantly higher with TA-ER than with placebo. Adverse events were reported more frequently with TA-ER than with placebo; the most common adverse events reported were nausea, dizziness, constipation, and vomiting. TA-ER was significantly more

  1. Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers.

    Science.gov (United States)

    de Hoon, Jan; Van Hecken, Anne; Vandermeulen, Corinne; Herbots, Marissa; Kubo, Yumi; Lee, Ed; Eisele, Osa; Vargas, Gabriel; Gabriel, Kristin

    2018-01-01

    Objectives The aim of this study was to assess the effects of concomitant administration of erenumab and sumatriptan on resting blood pressure, pharmacokinetics, safety, and tolerability in healthy subjects. Methods In this phase 1, parallel-group, one-way crossover, double-blind, placebo-controlled study, healthy adult subjects were randomized (1:2) to receive either intravenous placebo and subcutaneous sumatriptan 12 mg (i.e. two 6-mg injections separated by 1 hour) or intravenous erenumab 140 mg and subcutaneous sumatriptan 12 mg. Blood pressure was measured pre-dose and at prespecified times post-dose. The primary endpoint was individual time-weighted averages of mean arterial pressure, measured from 0 hours to 2.5 hours after the first dose of sumatriptan. Pharmacokinetic parameters for sumatriptan were evaluated by calculating geometric mean ratios (erenumab and sumatriptan/placebo and sumatriptan). Adverse events and anti-erenumab antibodies were also evaluated. Results A total of 34 subjects were randomized and included in the analysis. Least squares mean (standard error) time-weighted averages of mean arterial pressure were 87.4 (1.0) mmHg for the placebo and sumatriptan group and 87.4 (1.2) mmHg for the erenumab and sumatriptan group. Mean difference in mean arterial pressure between groups was -0.04 mmHg (90% confidence interval: -2.2, 2.1). Geometric mean ratio estimates for maximum plasma concentration of sumatriptan was 0.95 (90% confidence interval: 0.82, 1.09), area under the plasma concentration-time curve (AUC) from time 0 to 6 hours was 0.98 (90% confidence interval: 0.93, 1.03), and AUC from time 0 to infinity was 1.00 (90% confidence interval: 0.96, 1.05). No clinically relevant safety findings for co-administration of sumatriptan and erenumab were identified. Conclusion Co-administration of erenumab and sumatriptan had no additional effect on resting blood pressure or on pharmacokinetics of sumatriptan. ClinicalTrials.gov, NCT

  2. Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Ludolph, Albert C; Schuster, Joachim; Dorst, Johannes; Dupuis, Luc; Dreyhaupt, Jens; Weishaupt, Jochen H; Kassubek, Jan; Weiland, Ulrike; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Schrank, Berthold; Boentert, Matthias; Emmer, Alexander; Hermann, Andreas; Zeller, Daniel; Prudlo, Johannes; Winkler, Andrea S; Grehl, Torsten; Heneka, Michael T; Wollebæk Johannesen, Siw; Göricke, Bettina

    2018-06-18

    Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the

  3. Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis.

    Science.gov (United States)

    Murata, Yoko; Song, Michael; Kikuchi, Hisayuki; Hisamichi, Katsuya; Xu, Xie L; Greenspan, Andrew; Kato, Mai; Chiou, Chiun-Fang; Kato, Takeshi; Guzzo, Cynthia; Thurmond, Robin L; Ohtsuki, Mamitaro; Furue, Masutaka

    2015-02-01

    This trial was conducted to evaluate the safety and efficacy of the H4 R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4 R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect. © 2014 Japanese Dermatological Association.

  4. The efficacy and safety of lixivaptan in outpatients with heart failure and volume overload: results of a multicentre, randomized, double-blind, placebo-controlled, parallel-group study.

    Science.gov (United States)

    Ghali, Jalal K; Orlandi, Cesare; Abraham, William T

    2012-06-01

    Volume overload is the dominant feature of decompensated heart failure (HF) and it often results in adverse clinical outcomes. Vasopressin receptor antagonists such as lixivaptan may provide effective volume unloading. This study assessed weight loss after 1 day and 8 weeks of treatment with lixivaptan in outpatients with HF and volume overload. This phase II, 8-week, multicentre, double-blind, parallel-group study randomized participants (2:1) to receive lixivaptan 100 mg or placebo once daily (in addition to standard HF therapy). Body weight and cardiovascular assessments were made at baseline, Day 1 (not cardiovascular), Weeks 1, 2, 4, and 8, and 7 days post-treatment. The Trail-making Test, part B (TMT-B) and the Medical Outcomes Survey 6-item cognitive function scale (MOS-6) were assessed at baseline and Week 4. The study randomized 170 participants (lixivaptan, n = 111; placebo, n = 59). Most (97.1%) were receiving pharmacological therapy for HF at baseline. Demographic characteristics were generally similar between the two groups. Body weight decreased significantly from baseline to Day 1 with lixivaptan vs. placebo (least-square mean change ± standard error: - 0.38 ± 0.08 kg vs. +0.13 ± 0.11 kg; P overload, lixivaptan 100 mg once daily, when added to standard therapy, reduced body weight, improved dyspnoea and orthopnoea, and was well tolerated. NCT01055912.

  5. Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study.

    Science.gov (United States)

    Adler, Lenard A; Dirks, Bryan; Deas, Patrick; Raychaudhuri, Aparna; Dauphin, Matthew; Saylor, Keith; Weisler, Richard

    2013-10-09

    This study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD). This report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30-70 mg/d) in adults (18-55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL. Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, PPsychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies. Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies. ClinicalTrials.gov, NCT01101022.

  6. A randomized, double-blind, placebo-controlled, multiple-dose, parallel-group clinical trial to assess the effects of teduglutide on gastric emptying of liquids in healthy subjects.

    Science.gov (United States)

    Berg, Jolene Kay; Kim, Eric H; Li, Benjamin; Joelsson, Bo; Youssef, Nader N

    2014-02-12

    Teduglutide, a recombinant analog of human glucagon-like peptide (GLP)-2, is a novel therapy recently approved for the treatment of adult patients with short bowel syndrome who are dependent on parenteral support. Previous studies assessing the effect of GLP-2 on gastric emptying in humans have yielded inconsistent results, with some studies showing no effect and others documenting a GLP-2-dependent delay in gastric emptying. The primary objective of this study was to assess the effect of teduglutide on gastric emptying of liquids in healthy subjects, as measured by the pharmacokinetics of acetaminophen. This double-blind, parallel-group, single-center study enrolled and randomized 36 healthy subjects (22 men, 14 women) to receive subcutaneous doses of teduglutide 4 mg or placebo (2:1 ratio; 23:13) once daily on Days 1 through 10 in the morning. Gastric emptying of a mixed nutrient liquid meal was assessed by measuring acetaminophen levels predose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12, and 14 hours after administration of 1000 mg acetaminophen on Days 0 and 10. The primary study endpoint was a pharmacokinetic analysis of acetaminophen absorption in subjects receiving teduglutide or placebo. No significant differences in gastric emptying of liquids (acetaminophen area under the concentration [AUC] vs time curve from time 0 to the last measurable concentration, AUC extrapolated to infinity, maximum concentration [Cmax], and time to Cmax) were observed on Day 10 in subjects receiving teduglutide 4 mg versus subjects receiving placebo. There were no serious adverse events (AEs), deaths, or discontinuations due to an AE reported during the study. Teduglutide 4 mg/day for 10 days does not affect gastric emptying of liquids in healthy subjects as measured by acetaminophen pharmacokinetics. No unexpected safety signals were observed. This study was registered at ClinicalTrials.gov, identifier NCT01209351.

  7. Effect of a herbal extract powder (YY-312) from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode on body fat mass in overweight adults: a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial.

    Science.gov (United States)

    Cho, Young-Gyu; Jung, Ji-Hye; Kang, Jae-Heon; Kwon, Jin Soo; Yu, Seung Pil; Baik, Tae Gon

    2017-07-28

    YY-312 is a herbal extract powder from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode, which have health promoting effects, including body fat reduction. We aimed to evaluate the efficacy and safety of YY-312 for body fat reduction in overweight adults. This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial performed in overweight Korean adults aged 19-60 years with a body mass index of 25.0-29.9 kg/m 2 . The daily dose of YY-312 was 2400 mg (containing 1800 mg of active herbal extract and 600 mg of cyclodextrin). Primary outcomes were reductions in body fat mass (BFM) and body fat percentage (BF%) after 12 weeks. Secondary outcomes included reductions in body weight and waist circumference (WC) after 12 weeks. After 12 weeks, BFM (1.6 kg vs. 0.1 kg; P = 0.023) and BF% (1.5% vs. -0.2%; P = 0.018) decreased significantly more in the YY-312 group than in the placebo group, as did body weight (2.7 kg vs. 1.0 kg; P = 0.014) and WC (2.2 cm vs. 0.8 cm; P = 0.049). All safety parameters were within normal limits; no serious adverse events occurred in either group. In a 12-week clinical trial in overweight adults, YY-312 resulted in significantly greater reduction in body fat vs. placebo, while being safe and well tolerated. cris.nih.go.kr: ( KCT0001225 ).

  8. The effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc lactate on the microflora of oral halitosis patients : a dual-centre, double-blind placebo-controlled study

    NARCIS (Netherlands)

    Roldan, S; Winkel, EG; Herrera, D; Sanz, M; Van Winkelhoff, AJ

    Aim: This study evaluated the microbial effects of a newly formulated mouthwash (Halita((R)) ) on oral halitosis patients. Methods: Forty subjects were included in this dual-centre, double-blind, placebo-controlled parallel study. Inclusion and exclusion criteria were used to select patients. At

  9. Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker--Rationale and design of the trial.

    Science.gov (United States)

    Tomasik, Andrzej; Jacheć, Wojciech; Wojciechowska, Celina; Kawecki, Damian; Białkowska, Beata; Romuk, Ewa; Gabrysiak, Artur; Birkner, Ewa; Kalarus, Zbigniew; Nowalany-Kozielska, Ewa

    2015-05-01

    Dual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction. To present rationale and design of randomized blinded trial aimed to assess whether 12 month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF ≥ 40%) and first implantation of dual chamber pacemaker. A total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80 mg/daily and valsartan 160 mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12 month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging. If valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804). Copyright © 2015 Elsevier Inc. All rights reserved.

  10. 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

  11. A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Soluble Thrombomodulin, ART-123, in Patients With Sepsis and Suspected Disseminated Intravascular Coagulation

    NARCIS (Netherlands)

    Vincent, Jean-Louis; Ramesh, Mayakonda K.; Ernest, David; Larosa, Steven P.; Pachl, Jan; Aikawa, Naoki; Hoste, Eric; Levy, Howard; Hirman, Joe; Levi, Marcel; Daga, Mradul; Kutsogiannis, Demetrios J.; Crowther, Mark; Bernard, Gordon R.; Devriendt, Jacques; Puigserver, Joan Vidal; Blanzaco, Daniel U.; Esmon, Charles T.; Parrillo, Joseph E.; Guzzi, Louis; Henderson, Seton J.; Pothirat, Chaicharn; Mehta, Parthiv; Fareed, Jawed; Talwar, Deepak; Tsuruta, Kazuhisa; Gorelick, Kenneth J.; Osawa, Yutaka; Kaul, Inder

    2013-01-01

    Objectives: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. Design: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial.

  12. Exploratory double-blind, parallel-group, placebo-controlled extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    Science.gov (United States)

    2017-10-01

    Following the first phase III study of edaravone for amyotrophic lateral sclerosis (ALS), this extension study was performed to evaluate longer-term efficacy and safety. Patients given edaravone in the first 24-week phase III study (Cycles 1-6) were randomised to edaravone (E-E) or placebo (E-P) in the subsequent 24-week double-blind period (Cycles 7-12). Patients given placebo in phase III were switched to edaravone (P-E). Subsequently, all patients received edaravone for 12 weeks (Cycles 13-15). Efficacy endpoints included revised ALS Functional Rating Scale (ALSFRS-R) score. Analysis populations were the full analysis set (FAS) and the efficacy-expected subpopulation (EESP) defined by post-hoc analysis of the first phase III study. The least-squares mean and standard error of the intergroup difference (E-E vs. E-P) of change in the ALSFRS-R score from Cycles 7-12 was 1.16 ± 0.93 (p = 0.2176) in the FAS, and 1.85 ± 1.14 (p = 0.1127) in the EESP. The ALSFRS-R score changed almost linearly in the E-E group throughout Cycles 1-15 (60 weeks). The incidence of serious adverse events associated with ALS progression was higher in E-E than in E-P. Edaravone might have potential efficacy for up to 15 cycles when used to treat patients in the EESP with careful safety monitoring.

  13. Treatment of post-myocardial infarction depressive disorder : A randomized, placebo-controlled trial with mirtazapine

    NARCIS (Netherlands)

    Honig, Adriaan; Kuyper, Astrid M. G.; Schene, Aart H.; van Melle, Joost P.; De Jonge, Peter; Tulner, Dorien M.; Schins, Annique; Crijns, Harry J. G. M.; Kuijpers, Petra M. J. C.; Vossen, Helen; Lousberg, Richel; Ormel, Johan

    Objective: To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective

  14. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, Oli Jacob; Hansen, Niels-Christian Gerner; Søes-Petersen, Ulrik

    2004-01-01

    Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...

  15. Heart rate acceleration with GLP-1 receptor agonists in type 2 diabetes patients : an acute and 12-week randomised, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, T.; Kramer, Mark H H; Diamant, Michaela; van Raalte, Daniël H

    OBJECTIVE: To examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients. DESIGN: Acute and 12-week randomised, placebo-controlled, double-blind, single-centre, parallel-group trial. METHODS: In total, 57 type 2 diabetes patients

  16. Dapagliflozin once-daily and exenatide once-weekly dual therapy: A 24-week randomized, placebo-controlled, phase II study examining effects on body weight and prediabetes in obese adults without diabetes.

    Science.gov (United States)

    Lundkvist, Per; Sjöström, C David; Amini, Sam; Pereira, Maria J; Johnsson, Eva; Eriksson, Jan W

    2017-01-01

    To explore the effects of dual therapy with dapagliflozin and exenatide on body weight, body composition, glycaemic variables and systolic blood pressure (SBP) in obese adults without diabetes. In this single-centre, double-blind trial, we randomized 50 obese adults without diabetes (aged 18-70 years; body mass index 30-45 kg/m 2 ) to oral dapagliflozin 10 mg once daily plus subcutaneous long-acting exenatide 2 mg once weekly or placebo. MRI was used to assess change in body composition. Participants were instructed to follow a balanced diet and exercise moderately. Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23 (92.0%) and 20 (80.0%) completed 24 weeks of treatment, respectively. At baseline, the mean participant age was 52 years, 61% were female, the mean body weight was 104.6 kg, and 73.5% of participants had prediabetes (impaired fasting glucose or impaired glucose tolerance). After 24 weeks, for dapagliflozin/exenatide versus placebo: the difference in body weight change was -4.13 kg (95% confidence interval -6.44, -1.81; P prediabetes was less frequent with active treatment (34.8% vs 85.0%, respectively; P prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  17. 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,

  18. [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

  19. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

    NARCIS (Netherlands)

    Boeckxstaens, Guy E.; Beaumont, Hanneke; Hatlebakk, Jan G.; Silberg, Debra G.; Björck, Karin; Karlsson, Maria; Denison, Hans

    2011-01-01

    o evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy. double-blind, placebo-controlled, randomised, parallel-group,

  20. 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

  1. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis.

    Science.gov (United States)

    Irving, Peter M; Iqbal, Tariq; Nwokolo, Chuka; Subramanian, Sreedhar; Bloom, Stuart; Prasad, Neeraj; Hart, Ailsa; Murray, Charles; Lindsay, James O; Taylor, Adam; Barron, Rachel; Wright, Stephen

    2018-03-19

    Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4-10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks' CBD-rich botanical extract or placebo capsules. The primary endpoint was the percentage of patients in remission after treatment. Statistical testing was 2-sided, using a 10% significance level. Patients were less tolerant of CBD-rich botanical extract compared with placebo, taking on average one-third fewer capsules, and having more compliance-related protocol deviations (principally insufficient exposure), prompting identification of a per protocol (PP) analysis set. The primary endpoint was negative; end of treatment remission rates were similar for CBD-rich botanical extract (28%) and placebo (26%). However, PP analysis of total and partial Mayo scores favoured CBD-rich botanical extract (P = 0.068 and P = 0.038, respectively). Additionally, PP analyses of the more subjective physician's global assessment of illness severity, subject global impression of change, and patient-reported quality-of-life outcomes were improved for patients taking CBD-rich botanical extract (P = 0.069, P = 0.003, and P = 0.065, respectively). Adverse events (AEs) were predominantly mild/moderate with many in the CBD-rich botanical extract group potentially attributable to the ∆9-tetrahydrocannabinol content. A greater proportion of gastrointestinal-related AEs, indicative of UC worsening, was seen on placebo. Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.

  2. Cognitive and Mood Effects of a Nutrient Enriched Breakfast Bar in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled, Parallel Groups Study

    Directory of Open Access Journals (Sweden)

    David O. Kennedy

    2017-12-01

    Full Text Available Objectives: Few previous studies have assessed the effects of concomitant administration of multiple potentially psychoactive nutrients. Methods: 95 healthy adult participants consumed either a nutrient enriched breakfast bar (containing α-Linolenic acid, l-tyrosine, l-theanine, vitamins, minerals and 21.5 mg of caffeine or an isocaloric, macronutrient matched control bar for 56 days. Cognitive function and mood were assessed pre-dose and at 40- and 160-min post-dose on the 1st and 56th day of the intervention period. Results: The results demonstrated acute effects of treatment across post-dose assessments on both assessment days in terms of alertness, and on tasks assessing attention, working and episodic memory and executive function, including cognitively demanding Serial subtraction and Rapid Visual Information Processing tasks. There were no evident chronic effects independent of the breakfast bars’ acute effects. Discussion: These results demonstrate that a nutrient enriched breakfast bar with low caffeine content can exert striking beneficial effects on acute cognitive function and alertness.

  3. The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study.

    Science.gov (United States)

    Schwizer, Werner; Menne, Dieter; Schütze, Kurt; Vieth, Michael; Goergens, Reiner; Malfertheiner, Peter; Leodolter, Andreas; Fried, Michael; Fox, Mark R

    2013-08-01

    This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.

  4. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Abe, Koji; Itoyama, Yasuto; Sobue, Gen; Tsuji, Shoji; Aoki, Masashi; Doyu, Manabu; Hamada, Chikuma; Kondo, Kazuoki; Yoneoka, Takatomo; Akimoto, Makoto; Yoshino, Hiide

    2014-12-01

    Our objective was to confirm the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients. We conducted a 36-week confirmatory study, consisting of 12-week pre-observation period followed by 24-week treatment period. Patients received placebo or edaravone i.v. infusion over 60 min for the first 14 days in cycle 1, and for 10 of the first 14 days during cycles 2 to 6. The efficacy primary endpoint was changed in the revised ALS functional rating scale (ALSFRS-R) scores during the 24-week treatment. Patients were treated with placebo (n = 104) and edaravone (n = 102). Changes in ALSFRS-R during the 24-week treatment were -6.35 ± 0.84 in the placebo group (n = 99) and -5.70 ± 0.85 in the edaravone group (n = 100), with a difference of 0.65 ± 0.78 (p = 0.411). Adverse events amounted to 88.5% (92/104) in the placebo group and 89.2% (91/102) in the edaravone group. In conclusion, the reduction of ALSFRS-R was smaller in the edaravone group than in the placebo group, but efficacy of edaravone for treatment of ALS was not demonstrated. Levels and frequencies of reported adverse events were similar in the two groups.

  5. Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment.

    Science.gov (United States)

    Pope, Harrison G; Amiaz, Revital; Brennan, Brian P; Orr, Guy; Weiser, Mark; Kelly, John F; Kanayama, Gen; Siegel, Arthur; Hudson, James I; Seidman, Stuart N

    2010-04-01

    Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men. We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed, hypogonadal men. For this study, we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower. We randomized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression Scale, and the Quality of Life Scale. Our primary analysis, using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures, failed to show a significant difference between groups (mean [95% confidence interval] 6-week change in HDRS for testosterone vs placebo, -0.4 [-2.6 to 1.8]). However, in one exploratory analysis of treatment responders, we found a possible trend in favor of testosterone on the HDRS. Our findings, combined with the conflicting data from earlier smaller studies, suggest that testosterone is not generally effective for depressed men. The possibility remains that testosterone might benefit a particular subgroup of depressed men, but if so, the characteristics of this subgroup would still need to be established.

  6. A Double-Blind, Placebo-Controlled, Parallel-Group Pilot Study of Milnacipran for Chronic Radicular Pain (Sciatica) Associated With Lumbosacral Disc Disease

    OpenAIRE

    Marks, David M.; Pae, Chi-Un; Patkar, Ashwin A.

    2014-01-01

    Objective: The current study investigates whether milnacipran, an equipotent serotonin-norepinephrine reuptake inhibitor, is effective in reducing chronic radicular pain in patients (N = 11) with lumbosacral disc disease.

  7. Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial.

    Science.gov (United States)

    Faurholt-Jepsen, M; Frost, M; Ritz, C; Christensen, E M; Jacoby, A S; Mikkelsen, R L; Knorr, U; Bardram, J E; Vinberg, M; Kessing, L V

    2015-10-01

    The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder. A total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups. Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group. These results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool.

  8. Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Henderson, V W; Paganini-Hill, A; Miller, B L; Elble, R J; Reyes, P F; Shoupe, D; McCleary, C A; Klein, R A; Hake, A M; Farlow, M R

    2000-01-25

    AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. Memantine in frontotemporal lobar degeneration: A multicenter, randomised, double-blind, placebo-controlled trial

    Science.gov (United States)

    Boxer, Adam L.; Knopman, David S.; Kaufer, Daniel I.; Grossman, Murray; Onyike, Chiadi; Graf-Radford, Neill; Mendez, Mario; Kerwin, Diana; Lerner, Alan; Wu, Chuang-Kuo; Koestler, Mary; Shapira, Jill; Sullivan, Kathryn; Klepac, Kristen; Lipowski, Kristine; Ullah, Jerin; Fields, Scott; Kramer, Joel H.; Merrilees, Jennifer; Neuhaus, John; Mesulam, M. Marsel; Miller, Bruce L.

    2013-01-01

    Background Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26 week open label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI). Methods We performed a randomized, parallel group, double blind, placebo controlled trial of 20 mg memantine taken orally daily for 26 weeks in FTD. Participants met Neary criteria for behavioral variant (bvFTD) or semantic dementia (SD) and had characteristic brain atrophy. Use of cholinesterase inhibitors was prohibited. The objective of the study was to determine whether memantine is an effective treatment for FTD. Individuals were randomized to memantine or matched placebo tablets in blocks of two and four. Primary endpoints were the change in total NPI score and Clinical Global Impression of Change (CGIC) scores after 26 weeks. Secondary outcomes included a neuropsychological battery, and other cognitive, global and activity of daily living measures. Clinicaltrials.gov identifier: NCT00545974 Findings 100 subjects were screened, 81 were randomized, 5 (6%) discontinued and 76 completed all visits. Enrollment numbers were lower than planned due to many subjects’ preference to take memantine or cholinesterase inhibitors off-label rather than participate in a clinical trial. 39 memantine and 42 placebo subjects entered the primary intent to treat analysis. There was no effect of memantine treatment on either the NPI (mean difference [MD] 2.2, 95%CI: −3.9, 8.3, p = 0.47) or CGIC (MD 0, 95%CI: −0.4, 0.4, p = 0.90) after 26 weeks of treatment. Memantine was generally well tolerated, however there were more frequent cognitive adverse events in the memantine group. Interpretation There was no benefit of memantine treatment in bvFTD or SD. These data do not support memantine use in FTD. Funding Forest Research Institute PMID:23290598

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

    DEFF Research Database (Denmark)

    Hansen, K.S.; Vestergaard, H.S.; Skov, P.S.

    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...... the pollen season and took place from 1997 to 1999. The freeze-dried apple material was characterized by means of leukocyte histamine release (HR), skin prick test (SPT), and immunoblotting experiments. The study population consisted of birch pollen-allergic patients with a history of rhinitis in the birch......-pollen season and positive specific IgE to birch. For comparison of the DBPCFC models, 65 patients with a positive open oral challenge with apple were selected. In the characterization of the freeze-dried apple material, 46 birch pollen-allergic patients were included. The IgE reactivity to apple was evaluated...

  17. Specific music therapy techniques in the treatment of primary headache disorders in adolescents: a randomized attention-placebo-controlled trial.

    Science.gov (United States)

    Koenig, Julian; Oelkers-Ax, Rieke; Kaess, Michael; Parzer, Peter; Lenzen, Christoph; Hillecke, Thomas Karl; Resch, Franz

    2013-10-01

    Migraine and tension-type headache have a high prevalence in children and adolescents. In addition to common pharmacologic and nonpharmacologic interventions, music therapy has been shown to be efficient in the prophylaxis of pediatric migraine. This study aimed to assess the efficacy of specific music therapy techniques in the treatment of adolescents with primary headache (tension-type headache and migraine). A prospective, randomized, attention-placebo-controlled parallel group trial was conducted. Following an 8-week baseline, patients were randomized to either music therapy (n = 40) or a rhythm pedagogic program (n = 38) designed as an "attention placebo" over 6 sessions within 8 weeks. Reduction of both headache frequency and intensity after treatment (8-week postline) as well as 6 months after treatment were taken as the efficacy variables. Treatments were delivered in equal dose and frequency by the same group of therapists. Data analysis of subjects completing the protocol showed that neither treatment was superior to the other at any point of measurement (posttreatment and follow-up). Intention-to-treat analysis revealed no impact of drop-out on these results. Both groups showed a moderate mean reduction of headache frequency posttreatment of about 20%, but only small numbers of responders (50% frequency reduction). Follow-up data showed no significant deteriorations or improvements. This article presents a randomized placebo-controlled trial on music therapy in the treatment of adolescents with frequent primary headache. Music therapy is not superior to an attention placebo within this study. These results draw attention to the need of providing adequate controls within therapeutic trials in the treatment of pain. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Roflumilast for the treatment of COPD in an Asian population: a randomized, double-blind, parallel-group study.

    Science.gov (United States)

    Zheng, Jinping; Yang, Jinghua; Zhou, Xiangdong; Zhao, Li; Hui, Fuxin; Wang, Haoyan; Bai, Chunxue; Chen, Ping; Li, Huiping; Kang, Jian; Brose, Manja; Richard, Frank; Goehring, Udo-Michael; Zhong, Nanshan

    2014-01-01

    Roflumilast is the only oral phosphodiesterase 4 inhibitor indicated for use in the treatment of COPD. Previous studies of roflumilast have predominantly involved European and North American populations. A large study was necessary to determine the efficacy and safety of roflumilast in a predominantly ethnic Chinese population. In a placebo-controlled, double-blind, parallel-group, multicenter, phase 3 study, patients of Chinese, Malay, and Indian ethnicity (N = 626) with severe to very severe COPD were randomized 1:1 to receive either roflumilast 500 μg once daily or placebo for 24 weeks. The primary end point was change in prebronchodilator FEV1 from baseline to study end. Three hundred thirteen patients were assigned to each treatment. Roflumilast provided a sustained increase over placebo in mean prebronchodilator FEV1 (0.071 L; 95% CI, 0.046, 0.095 L; P < .0001). Similar improvements were observed in the secondary end points of postbronchodilator FEV1 (0.068 L; 95% CI 0.044, 0.092 L; P < .0001) and prebronchodilator and postbronchodilator FVC (0.109 L; 95% CI, 0.061, 0.157 L; P < .0001 and 0.101 L; 95% CI, 0.055, 0.146 L; P < .0001, respectively). The adverse event profile was consistent with previous roflumilast studies. The most frequently reported treatment-related adverse event was diarrhea (6.0% and 1.0% of patients in the roflumilast and placebo groups, respectively). Roflumilast plays an important role in lung function improvement and is well tolerated in an Asian population. It provides an optimal treatment choice for patients with severe to very severe COPD.

  19. 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

  20. 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.

  1. Randomised, double-blinded, placebo-controlled, clinical trial of ozone therapy as treatment of sudden sensorineural hearing loss.

    Science.gov (United States)

    Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M

    2009-01-01

    To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p < 0.05). Mean hearing gains, pure tone averages, speech reception thresholds and subjective recovery rates were significantly better in ozone-treated patients compared with placebo-treated patients (p < 0.05). Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.

  2. 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.

  3. Emotional changes in men treated with sildenafil citrate for erectile dysfunction: a double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Moncada, Ignacio; Martínez-Jabaloyas, José M; Rodriguez-Vela, Luis; Gutiérrez, Pedro R; Giuliano, Francois; Koskimaki, Juha; Farmer, Ian S; Renedo, Virginia Pascual; Schnetzler, Gabriel

    2009-12-01

    Erectile dysfunction (ED) has been associated with several comorbidities and can cause significant loss of quality of life and self-esteem. In men with ED, to use the validated Self-Esteem and Relationship (SEAR) questionnaire to evaluate changes in self-esteem associated with sildenafil treatment of ED and to assess changes dependent on concomitant comorbid conditions. This was a 14-week, international, randomized, parallel-group, double-blind, flexible-dose (25, 50, or 100 mg), placebo-controlled study of sildenafil in men aged >or=18 years with a clinical diagnosis of ED (score Erectile Function (IIEF) domain scores and in the intercourse success rate, and the response to the global efficacy assessment and to the global satisfaction assessment. A total of 841 patients were included in the intent-to-treat efficacy analysis (559 sildenafil, 282 placebo). Patients randomized to sildenafil had significantly greater change scores from baseline to the end of treatment on all components of the SEAR and all domains of the IIEF (P Erectile Function domain score (r = 0.6338, P emotional benefits of sildenafil in the treatment of ED were confirmed, overall and in men with comorbid hypertension, hyperlipidemia, benign prostatic hypertrophy, and/or depression. Using both the IIEF and the SEAR questionnaires provides a more complete assessment of ED.

  4. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, O.J.; Gerner Hansen, Niels-Christian; Soes-Petersen, U.

    2004-01-01

    (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking......Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...... more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark....

  5. Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial

    NARCIS (Netherlands)

    Beuers, U.; Spengler, U.; Kruis, W.; AYDEMIR, U.; WIEBECKE, B.; HELDWEIN, W.; WEINZIERL, M.; Pape, G. R.; Sauerbruch, T.; Paumgartner, G.

    1992-01-01

    The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver

  6. 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

  7. 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

  8. 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 ...

  9. 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.

  10. Exploratory double-blind, parallel-group, placebo-controlled study of edaravone (MCI-186) in amyotrophic lateral sclerosis (Japan ALS severity classification: Grade 3, requiring assistance for eating, excretion or ambulation).

    Science.gov (United States)

    2017-10-01

    Our objective was to explore the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients with a Japan ALS severity classification of Grade 3. In a 24-week, double-blind, randomized study, 25 patients who met all of the following criteria were enrolled: Japan ALS severity classification Grade 3; definite, probable, or probable-laboratory supported ALS (El Escorial/revised Airlie House); forced vital capacity (%FVC) ≥60%; duration of disease ≤3 years at consent; and change in the revised ALS functional rating scale (ALSFRS-R) score of -1 to -4 points during the 12-week pre-observation period. Patients received edaravone (n = 13) or placebo (n = 12) for six cycles. The efficacy outcome was change in the ALSFRS-R score. The least-squares mean change in the ALSFRS-R score ± standard error during the 24-week treatment was -6.52 ± 1.78 in the edaravone group and -6.00 ± 1.83 in the placebo group; the difference of -0.52 ± 2.46 was not statistically significant (p = 0.835). Incidence of adverse events was 92.3% (12/13) in the edaravone group and 100.0% (12/12) in the placebo group. There was no intergroup difference in the changes in the ALSFRS-R score. The incidences of adverse events were similar in the two groups.

  11. Post-hoc analysis of MCI186-17, the extension study to MCI186-16, the confirmatory double-blind, parallel-group, placebo-controlled study of edaravone in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Takahashi, Fumihiro; Takei, Koji; Tsuda, Kikumi; Palumbo, Joseph

    2017-10-01

    In the 24-week double-blind study of edaravone in ALS (MCI186-16), edaravone did not show a statistically significant difference versus placebo for the primary efficacy endpoint. For post-hoc analyses, two subpopulations were identified in which edaravone might be expected to show efficacy: the efficacy-expected subpopulation (EESP), defined by scores of ≥2 points on all 12 items of the ALS Functional Rating Scale-Revised (ALSFRS-R) and a percent predicted forced vital capacity (%FVC) ≥80% at baseline; and the definite/probable EESP 2 years (dpEESP2y) subpopulation which, in addition to EESP criteria, had definite or probable ALS diagnosed by El Escorial revised criteria, and disease duration of ≤2 years. In the 36-week extension study of MCI186-16, a 24-week double-blind comparison followed by 12 weeks of open-label edaravone (MCI186-17; NCT00424463), analyses of ALSFRS-R scores of the edaravone-edaravone group and edaravone-placebo group for the full analysis set (FAS) and EESP, as prospectively defined, were reported in a previous article. Here we additionally report results in patients who met dpEESP2y criteria at the baseline of MCI186-16. In the dpEESP2y, the difference in ALSFRS-R changes from 24 to 48 weeks between the edaravone-edaravone and edaravone-placebo groups was 2.79 (p = 0.0719), which was greater than the differences previously reported for the EESP and the FAS. The pattern of adverse events in the dpEESP2y did not show any additional safety findings to those from the earlier prospective study. In conclusion, this post-hoc analysis suggests a potential effect of edaravone between 24 and 48 weeks in patients meeting dpEESP2y criteria at baseline.

  12. Add-on treatment with N-acetylcysteine for bipolar depression:a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol)

    OpenAIRE

    Ellegaard, Pernille Kempel; Licht, Rasmus Wentzer; Poulsen, Henrik Enghusen; Nielsen, René Ernst; Berk, Michael; Dean, Olivia May; Mohebbi, Mohammadreza; Nielsen, Connie Thuroee

    2018-01-01

    BACKGROUND: Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects o...

  13. Efficacy and safety of 1 % terbinafine film-forming solution in Chinese patients with tinea pedis: a randomized, double-blind, placebo-controlled, multicenter, parallel-group study.

    Science.gov (United States)

    Li, Ruo Yu; Wang, A P; Xu, J H; Xi, L Y; Fu, M H; Zhu, M; Xu, M L; Li, X Q; Lai, W; Liu, W D; Lu, X Y; Gong, Z Q

    2014-03-01

    Superficial fungal skin infections are treated using topical antifungals. The aim of this study was to demonstrate the efficacy of a single application of 1 % terbinafine film-forming solution (FFS) versus placebo for the treatment of tinea pedis in the Chinese population. Six centers in China randomized 290 patients in a 1:1 ratio to receive either 1 % terbinafine FFS or FFS vehicle (placebo) once on the affected foot/feet. Efficacy assessments included microscopy and mycologic culture, and assessing clinical signs and symptoms at baseline, and at weeks 1 and 6 after the topical treatment. All adverse events were recorded. At week 6, 1 % terbinafine FFS was superior to placebo for effective treatment rate (63 vs. 8 %); clinical cure (30 vs. 6 %); mycological cure (86 vs. 12 %); negative microscopy (90 vs. 24 %); and negative mycological culture (90 vs. 27 %): all p ≤ 0.001 and clinically relevant. At week 6, 1 % terbinafine FFS was clinically superior to placebo for the absence of: erythema (69 vs. 29 %); desquamation (33 vs. 8 %); and pruritus (70 vs. 30 %): all p ≤ 0.001 and clinically relevant. At week 6, differences in the average total signs and symptoms scores were significantly lower for 1 % terbinafine FFS versus placebo (p ≤ 0.001). Both 1 % terbinafine FFS and placebo were safe and well tolerated based on adverse events and investigator and patient assessments. This double-blind, randomized, multicenter study demonstrated one single topical application of 1 % terbinafine FFS was safe and effective in the treatment of tinea pedis in the Chinese population.

  14. Long-term maintenance of weight loss with sibutramine in a GP setting following a specialist guided very-low-calorie diet: a double-blind, placebo-controlled, parallel group study

    NARCIS (Netherlands)

    Mathus-Vliegen, E. M. H.

    2005-01-01

    Objective: Very-low-calorie diets (VLCDs) are used to promote short-term weight loss in obese patients. However, long-term maintenance of weight loss is generally poor. We assessed the efficacy and safety of sibutramine in maintaining weight loss achieved in obese patients by means of a 3-month

  15. A Randomized, Placebo-Controlled, Double-Blind, Parallel Groups Study Evaluating the Performance and Safety of a Steady State Coherent Biomodulator Patch in the Treatment of Subjective Tinnitus.

    Science.gov (United States)

    Ahnblad, Peter; Nordkvist, Anders

    2017-12-01

    The objectives of this study were to evaluate the performance and safety of an innovative passive light photon driven microscopic biomodulator patch as an alternative medical device for tinnitus relief. Eighty-two (82) patients were randomized to receive either an active (biomodulator) patch or a placebo patch, for a 3-week treatment period. Patch performance (evaluated with questionnaires related to tinnitus and quality-of-life) and safety were assessed after 3 weeks of treatment (Week 3) and at a follow-up visit 4-weeks after end of treatment (Week 7). The biomodulator patch was safe and well-tolerated and was efficacious, with significant difference (p < 0.05) between the groups at Week 7; active patch had 30% responders compared to 10% for placebo, measured as a decrease from baseline in at least 2 points in tinnitus annoyance visual analogue scale (VAS, 0-10). Tinnitus handicap inventory (THI, 0-100) improved by mean -16 points significantly (p = 0.0005) for the active responder group, but with no statistically significant changes for the placebo group or between the groups. Well-being questionnaire also improved for the active responder group, but not statistically significant. The placebo responder group did not improve in well-being. Other tinnitus related symptoms did not show significant changes. There was no statistically significant difference in performance between the active (biomodulator) and placebo groups directly at the end of treatment (Week 3). In a cost-risk-benefit rationale according to this study it can be reasonable to recommend the biomodulator patch for treatment of tinnitus. Improvements were shown at Week 7 (4 weeks after the end of treatment period).

  16. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

    DEFF Research Database (Denmark)

    Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus

    2010-01-01

    status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets....... Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained...

  17. Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study.

    Science.gov (United States)

    Higashi, Yoshinobu; Kiuchi, Takehito; Furuta, Kenichi

    2010-01-01

    An occlusive patch formulation containing 10% methyl salicylate and 3% l-menthol was recently approved by the US Food and Drug Administration for the treatment of mild to moderate pain. Despite widespread use of counterirritants, including methyl salicylate and menthol, for topical pain relief, published efficacy and safety data regarding the use of the agents alone or in combination are limited. The goal of this study was to determine the efficacy and safety profile of a patch containing 10% methyl salicylate and 3% l-menthol compared with a placebo patch in adult patients with mild to moderate muscle strain. Eligible patients were men or women aged >or=18 years with a clinical diagnosis of mild to moderate muscle strain. Patients were randomly assigned to receive either 1 active patch or 1 placebo patch applied to the skin at the affected area (ie, shoulder, upper back, upper arm, neck, calf, thigh, forearm, abdomen). Pain intensity was assessed on a 100-mm visual analog scale while at rest and with movement for 12 hours after patch application. The primary efficacy end point was the summed pain intensity difference score through 8 hours (SPID8) with movement. Analyses included use of descriptive statistics and an ANOVA model. Safety data, including adverse events, and secondary efficacy end points were also evaluated. A total of 208 patients (104 men, 104 women; age range, 18-78 years) were randomized to 1 of 2 study groups (105 in the active-patch group [mean age, 37.3 years], 103 in the placebo-patch group [mean age, 38.1 years]). The primary efficacy analysis (SPID8 with movement) indicated that patients receiving the active patch experienced significantly greater pain relief (approximately 40%) than those patients receiving a placebo patch (mean [SD], 182.6 [131.2] vs 130.1 [144.1]; P = 0.005). Analysis of the per-protocol population also found significantly more relief (P = 0.024) in the active-patch group (176.2 [131.4]; n = 92) versus the placebo-patch group (130.2 [144.0]; n = 96). Statistical analysis of secondary efficacy measures supported the primary end-point results. The number of patients experiencing any type of adverse event was comparable between study groups (active patch, 6.7% [7 events]; placebo patch, 5.8% [6 events]). No serious adverse events were reported during the study. A single, 8-hour application of a patch containing methyl salicylate and l-menthol provided significant relief of pain associated with mild to moderate muscle strain in these adult patients compared with patients receiving a placebo patch.

  18. Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy

    Science.gov (United States)

    Grangé, Gilles; Jacob, Nelly; Tanguy, Marie-Laure

    2014-01-01

    Objective To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). Design Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. Setting 23 maternity wards in France. Participants 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. Interventions Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. Main outcome measures The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. Results Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self

  19. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial.

    Science.gov (United States)

    Boggs, Douglas L; Surti, Toral; Gupta, Aarti; Gupta, Swapnil; Niciu, Mark; Pittman, Brian; Schnakenberg Martin, Ashley M; Thurnauer, Halle; Davies, Andrew; D'Souza, Deepak C; Ranganathan, Mohini

    2018-07-01

    Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. https://clinicaltrials.gov/ct2/show/NCT00588731.

  20. Inhaled budesonide for adults with mild-to-moderate asthma: a randomized placebo-controlled, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Ana Luisa Godoy Fernandes

    2001-09-01

    Full Text Available CONTEXT: Budesonide is an inhaled corticosteroid with high topical potency and low systemic activity recommended in the treatment of chronic asthma. OBJECTIVE: This study was conducted to determine the efficacy and safety of inhaled budesonide via a breath-activated, multi-dose, dry-powder inhaler. TYPE OF STUDY: Multicenter randomized parallel-group, placebo-controlled, double-blind, clinical trial. SETTING: Multicenter study in the university units. PARTICIPANTS: Adult patients with mild-to-moderate asthma that was not controlled using bronchodilator therapy alone. PROCEDURES: Comparison of budesonide 400 µg administered twice daily via a breath-activated, multi-dose, dry-powder inhaler with placebo, in 43 adult patients (aged 15 to 78 years with mild-to-moderate asthma (FEV1 71% of predicted normal that was not controlled using bronchodilator therapy alone. MAIN MEASUREMENTS: Efficacy was assessed by pulmonary function tests and asthma symptom control (as perceived by the patients and the use of rescue medication. RESULTS: Budesonide 400 µg (bid was significantly more effective than placebo in improving morning peak expiratory flow (mean difference: 67.9 l/min; P < 0.005 and FEV1 (mean difference: 0.60 l; P < 0.005 over the 8-week treatment period. Onset of action, assessed by morning peak expiratory flow, occurred within the first two weeks of treatment. CONCLUSIONS: Budesonide via a breath-activated, multi-dose, dry-powder inhaler results in a rapid onset of asthma control, which is maintained over time and is well tolerated in adults with mild-to-moderate asthma.

  1. A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia

    Directory of Open Access Journals (Sweden)

    Amy S Chappell

    2008-12-01

    Full Text Available Amy S Chappell1, Laurence A Bradley2, Curtis Wiltse1, Michael J Detke1,3,4, Deborah N D’Souza1, Michael Spaeth51Lilly Research Laboratories, Indianapolis, IN, USA; 2University of Alabama at Birmingham, Birmingham, Alabama, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Harvard Medical School, Boston, MA, USA; 5Practice for Internal Medicine/Rheumatology, Graefelfing, GermanyObjective: Assess the efficacy of duloxetine 60/120 mg (N = 162 once daily compared with placebo (N = 168 in the treatment of patients with fibromyalgia, during six months of treatment.Methods: This was a phase-III, randomized, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of duloxetine.Results: There were no significant differences between treatment groups on the co-primary efficacy outcome measures, change in the Brief Pain Inventory (BPI average pain severity from baseline to endpoint (P = 0.053 and the Patient’s Global Impressions of Improvement (PGI-I at endpoint (P = 0.073. Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Questionnaire pain score, BPI least pain score and average interference score, Clinical Global Impressions of Severity scale, area under the curve of pain relief, Multidimensional Fatigue Inventory mental fatigue dimension, Beck Depression Inventory-II total score, and 36-item Short Form Health Survey mental component summary and mental health score. Nausea was the most common treatment-emergent adverse event in the duloxetine group. Overall discontinuation rates were similar between groups.Conclusions: Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co-primary outcome measures, in this supportive study, duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures.Keywords: fibromyalgia, duloxetine, placebo, double-blind, trial

  2. The protocol of the Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial.

    Science.gov (United States)

    Neerland, Bjørn Erik; Hov, Karen Roksund; Bruun Wyller, Vegard; Qvigstad, Eirik; Skovlund, Eva; MacLullich, Alasdair M J; Bruun Wyller, Torgeir

    2015-02-10

    Delirium affects 15% of hospitalised patients and is linked with poor outcomes, yet few pharmacological treatment options exist. One hypothesis is that delirium may in part result from exaggerated and/or prolonged stress responses. Dexmedetomidine, a parenterally-administered alpha2-adrenergic receptor agonist which attenuates sympathetic nervous system activity, shows promise as treatment in ICU delirium. Clonidine exhibits similar pharmacodynamic properties and can be administered orally. We therefore wish to explore possible effects of clonidine upon the duration and severity of delirium in general medical inpatients. The Oslo Study of Clonidine in Elderly Patients with Delirium (LUCID) is a randomised, placebo-controlled, double-blinded, parallel group study with 4-month prospective follow-up. We will recruit 100 older medical inpatients with delirium or subsyndromal delirium in the acute geriatric ward. Participants will be randomised to oral clonidine or placebo until delirium free for 2 days (Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria), or after a maximum of 7 days treatment. Assessment of haemodynamics (blood pressure, heart rate and electrocardiogram) and delirium will be performed daily until discharge or a maximum of 7 days after end of treatment. The primary endpoint is the trajectory of delirium over time (measured by Memorial Delirium Assessment Scale). Secondary endpoints include the duration of delirium, use of rescue medication for delirium, pharmacokinetics and pharmacodynamics of clonidine, cognitive function after 4 months, length of hospital stay and need for institutionalisation. LUCID will explore the efficacy and safety of clonidine for delirium in older medical inpatients. ClinicalTrials.gov NCT01956604. EudraCT Number: 2013-000815-26.

  3. Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

    Science.gov (United States)

    Ball, M Patricia; Warren, Kimberly R; Feldman, Stephanie; McMahon, Robert P; Kelly, Deanna L; Buchanan, Robert W

    2011-04-01

    In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

  4. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

    Science.gov (United States)

    Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

    2016-11-15

    Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

  5. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Papakostas, George I; Fava, Maurizio; Baer, Lee; Swee, Michaela B; Jaeger, Adrienne; Bobo, William V; Shelton, Richard C

    2015-12-01

    The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.

  6. 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.

  7. Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Morice, Alyn H; McGarvey, Lorcan; Pavord, Ian D; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S

    2017-07-01

    To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. ClinicalTrials.gov: NCT01656668.

  8. Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

    Science.gov (United States)

    Stott, David J; Gussekloo, Jacobijn; Kearney, Patricia M; Rodondi, Nicolas; Westendorp, Rudi G J; Mooijaart, Simon; Kean, Sharon; Quinn, Terence J; Sattar, Naveed; Hendry, Kirsty; Du Puy, Robert; Den Elzen, Wendy P J; Poortvliet, Rosalinde K E; Smit, Jan W A; Jukema, J Wouter; Dekkers, Olaf M; Blum, Manuel; Collet, Tinh-Hai; McCarthy, Vera; Hurley, Caroline; Byrne, Stephen; Browne, John; Watt, Torquil; Bauer, Douglas; Ford, Ian

    2017-02-03

    Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.

  9. The analgesic efficacy of intravenous lidocaine infusion after laparoscopic fundoplication: a prospective, randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Dale GJ

    2016-12-01

    Full Text Available Gregory J Dale,1 Stephanie Phillips,2 Gregory L Falk3 1Westmead Hospital Clinical School, The University of Sydney, 2Sydney Adventist Hospital Clinical School, The University of Sydney, 3Concord Clinical School, The University of Sydney, Sydney, Australia Abstract: This study aimed to determine if intravenous lidocaine infusion reduces postoperative pain intensity following laparoscopic fundoplication surgery and to also validate the safety of intravenous lidocaine at the dose tested. This was an equally randomized, double-blind, placebo-controlled, parallel-group, single center trial. Adult patients undergoing laparoscopic fundoplication were recruited. The intervention group received 1 mg/kg intravenous lidocaine bolus prior to induction of anesthesia, then an intravenous infusion at 2 mg/kg/h for 24 hours. The primary outcome was pain, measured using a numeric rating scale for 30 hours postoperatively. Secondary outcomes were nausea and vomiting, opioid requirements, adverse events, serum lidocaine concentration, and length of hospital stay. The study was terminated after an interim analysis of 24 patients showed evidence of futility. There was no difference in postoperative pain scores (lidocaine versus control, mean ± standard deviation at rest (2.0 ± 2.7 vs 2.1 ± 2.4, P=0.286 or with movement (2.0 ± 2.6 vs 2.6 ± 2.7, P=0.487. Three adverse events occurred in the lidocaine group (25% of patients. Intravenous lidocaine did not provide clinically significant analgesia to patients undergoing laparoscopic fundoplication. The serum lidocaine concentration of patients who experienced adverse events were within the therapeutic range. This trial cannot confirm the safety of intravenous lidocaine at the dose tested. Keywords: analgesia, local anesthetics, intravenous infusions, pharmacokinetics

  10. Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-08-01

    Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; pvaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

  11. 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

  12. 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...

  13. 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.

  14. No matrix effect in double-blind, placebo-controlled egg challenges in egg allergic children

    NARCIS (Netherlands)

    Libbers, L.; Flokstra-de Blok, B. M. J.; Vlieg-Boerstra, B. J.; van der Heide, S.; van der Meulen, G. N.; Kukler, J.; Kerkhof, M.; Dubois, A. E. J.

    Background Diagnostic and accidental food allergic reactions may be modified by the matrix containing the allergenic food. Previous studies of double-blind, placebo-controlled food challenges (DBPCFCs) with peanut found an effect of the fat content of the challenge matrix on the severity of the

  15. A double-blind placebo controlled trial of paroxetine in the ...

    African Journals Online (AJOL)

    A double-blind placebo controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa. Dan J. Stein, Michael Berk, Charl Els, Robin A. Emsley, Leon Gittelson, Don Wilson, Rosemary Oakes, Brian Hunter ...

  16. 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.

  17. Exclusively breastfed infants at risk for false negative double blind placebo controlled milk challenge

    NARCIS (Netherlands)

    Petrus, N. C. M.; Kole, E. A.; Schoemaker, A. A.; van Aalderen, W. M. C.; Sprikkelman, A. B.

    2014-01-01

    The double blind placebo controlled food challenge (DBPCFC) is the gold standard for diagnosing cow's milk allergy (CMA). However, false-negative DBPCFC have been reported. We present 2 cases with a false negative DBPCFC in exclusively breastfed infants suspected of CMA. These cases highlight the

  18. 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...

  19. Escitalopram in the Treatment of Adolescent Depression: A Randomized Placebo-Controlled Multisite Trial

    Science.gov (United States)

    Emslie, Graham J.; Ventura, Daniel; Korotzer, Andrew; Tourkodimitris, Stavros

    2009-01-01

    A randomized, double-blind, placebo-controlled trial that involves 312 male and female patients aged 12-17 reveal the effectiveness of escitalopram in the treatment of depressed adolescents. Eighty-three percent of the participants or 259 participants completed the 8 weeks therapy period.

  20. 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).

  1. 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

  2. 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],

  3. 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

  4. 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

  5. Working Memory Training in Young Children with ADHD: A Randomized Placebo-Controlled Trial

    Science.gov (United States)

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

    2014-01-01

    Background: Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the efficacy of Cogmed Working Memory Training…

  6. 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

  7. 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

  8. 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....

  9. Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema

    Directory of Open Access Journals (Sweden)

    Gandy JJ

    2011-09-01

    Full Text Available Justin J Gandy, Jacques R Snyman, Constance EJ van RensburgDepartment of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South AfricaBackground: The purpose of this study was to evaluate the efficacy and safety of carbohydrate-derived fulvic acid (CHD-FA in the treatment of eczema in patients two years and older.Methods: In this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks.Results: All safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results.Conclusion: CHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.Keywords: fulvic acid, eczema, anti-inflammatory, efficacy, safety

  10. Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference.

    Science.gov (United States)

    Black, Jed; Pillar, Giora; Hedner, Jan; Polo, Olli; Berkani, Ouali; Mangialaio, Sara; Hmissi, Abdel; Zammit, Gary; Hajak, Goran

    2017-08-01

    The orally active dual OX 1 R and OX 2 R antagonist, almorexant, targets the orexin system for the treatment of primary insomnia. This clinical trial assessed the effect of almorexant on sleep maintenance and other sleep endpoints, and its safety and tolerability in adults. Prospective, randomized, double-blind, placebo-controlled, active referenced trial in male and female adults aged 18-64 years with chronic, primary insomnia. Patients were randomized 1:1:1:1 to receive placebo, almorexant 100 mg, almorexant 200 mg, or zolpidem 10 mg (active reference) for 16 days. Primary efficacy assessments were objective (polysomnography-measured) and subjective (patient-recorded) wake time after sleep onset (WASO). Further sleep variables were also evaluated. From 709 randomized patients, 707 (mean age 45.4 years; 61.7% female) received treatment and 663 (93.8%) completed the study. A significant decrease versus placebo in median objective WASO was observed with almorexant 200 mg at the start and end of randomized treatment (-26.8 min and -19.5 min, respectively; both p system in insomnia disorder. CLINICALTRIALS. NCT00608985. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial.

    Directory of Open Access Journals (Sweden)

    Gijs H Goossens

    Full Text Available BACKGROUND: Blockade of the renin-angiotensin system (RAS reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM. METHODOLOGY/PRINCIPAL FINDINGS: We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d or placebo (PLB for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF ((133Xe wash-out, systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp. VAL treatment markedly reduced adipocyte size (P<0.001, with a shift toward a higher proportion of small adipocytes. In addition, fasting (P = 0.043 and postprandial ATBF (P = 0.049 were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP-1, TNF-α, adiponectin and leptin concentrations. CONCLUSIONS/SIGNIFICANCE: 26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL

  12. Effects of garcinia cambogia (Hydroxycitric Acid on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Kohsuke Hayamizu, MS

    2003-09-01

    Full Text Available Background: (--Hydroxycitric acid (HCA is an active ingredient extracted from the rind of the Indian fruit Garcinia cambogia. It inhibits adenosine triphosphate citrate lyase and has been used in the treatment of obesity. Objective: The primary end point of this study was the effects of 12 weeks of G cambogia extract administration on visceral fat accumulation. The secondary end points were body indices (including height, body weight, body mass index [BMI], waist and hip circumference, and waist–hip ratio and laboratory values (including total cholesterol, triacylglycerol, and free fatty acid. Methods: This study was performed according to a double-blind, randomized, placebo-controlled, parallel-group design. Subjects aged 20 to 65 years with a visceral fat area >90 cm2 were enrolled. Subjects were randomly assigned to receive treatment for 12 weeks with G cambogia (containing 1000 mg of HCA per day or placebo. At the end of the treatment period, both groups were administered placebo for 4 weeks to assess any rebound effect. Each subject underwent a computed tomography scan at the umbilical level at −2, 0, 12, and 16 weeks. Results: Forty-four subjects were randomized at baseline, and 39 completed the study (G cambogia group, n=18; placebo group, n=21. At 16 weeks, the G cambogia group had significantly reduced visceral, subcutaneous, and total fat areas compared with the placebo group (all indices P<0.001. No severe adverse effect was observed at any time in the test period. There were no significant differences in BMI or body weight at week 12, but there were slight numeric decreases in body weight and BMI in men. There were no signs of a rebound effect from week 12 to week 16. Conclusion: G cambogia reduced abdominal fat accumulation in subjects, regardless of sex, who had the visceral fat accumulation type of obesity. No rebound effect was observed. It is therefore expected that G cambogia may be useful for the prevention and reduction

  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. Effect of an herbal/botanical supplement on strength, balance, and muscle function following 12-weeks of resistance training: a placebo controlled study.

    Science.gov (United States)

    Furlong, Jonathan; Rynders, Corey A; Sutherlin, Mark; Patrie, James; Katch, Frank I; Hertel, Jay; Weltman, Arthur

    2014-01-01

    StemSport (SS; StemTech International, Inc. San Clemente, CA) contains a proprietary blend of the botanical Aphanizomenon flos-aquae and several herbal antioxidant and anti-inflammatory substances. SS has been purported to accelerate tissue repair and restore muscle function following resistance exercise. Here, we examine the effects of SS supplementation on strength adaptations resulting from a 12-week resistance training program in healthy young adults. Twenty-four young adults (16 males, 8 females, mean age = 20.5 ± 1.9 years, mass = 70.9 ± 11.9 kg, stature = 176.6 ± 9.9 cm) completed the twelve week training program. The study design was a double-blind, placebo controlled parallel group trial. Subjects either received placebo or StemSport supplement (SS; mg/day) during the training. 1-RM bench press, 1-RM leg press, vertical jump height, balance (star excursion and center of mass excursion), isokinetic strength (elbow and knee flexion/extension) and perception of recovery were measured at baseline and following the 12-week training intervention. Resistance training increased 1-RM strength (p 0.10). These data suggest that compared to placebo, the SS herbal/botanical supplement did not enhance training induced adaptations to strength, balance, and muscle function above strength training alone.

  15. A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy.

    Science.gov (United States)

    Mulhall, John P; Burnett, Arthur L; Wang, Run; McVary, Kevin T; Moul, Judd W; Bowden, Charles H; DiDonato, Karen; Shih, Winnie; Day, Wesley W

    2013-06-01

    We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy. This was a double-blind, placebo controlled, parallel group, phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy. Patients were randomized to 100 or 200 mg avanafil or placebo (taken 30 minutes before sexual activity) for 12 weeks. Primary end points included successful vaginal insertion (Sexual Encounter Profile [SEP] question 2), successful intercourse (SEP3) and change in score on the erectile function domain of the International Index of Erectile Function (IIEF-EF) questionnaire. A total of 298 patients were randomized and 84.6% completed the study. At baseline 16.1% were age 65 years or older and 71.5% had severe erectile dysfunction (mean overall IIEF-EF domain score 9.2). After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo (p erectile function after prostatectomy. Results suggest a rapid onset of action and sustained duration of effect, with all 3 primary end points being achieved at both dose levels. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. Effects of pumpkin seed in men with lower urinary tract symptoms due to benign prostatic hyperplasia in the one-year, randomized, placebo-controlled GRANU study.

    Science.gov (United States)

    Vahlensieck, Winfried; Theurer, Christoph; Pfitzer, Edith; Patz, Brigitte; Banik, Norbert; Engelmann, Udo

    2015-01-01

    The German Research Activities on Natural Urologicals (GRANU) study was a randomized, partially blinded, placebo-controlled, parallel-group trial that investigated the efficacy of pumpkin seed in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). A total of 1,431 men (50-80 years) with BPH/LUTS were randomly assigned to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or matching placebo. The primary response criterion was a decrease in International Prostate Symptom Score (IPSS) of ≥5 points from baseline after 12 months. Secondary outcome measures included IPSS-related quality of life, IPSS single items and diary-recorded nocturia. After 12 months, the response rate (intention-to-treat/last-observation-carried-forward approach) did not differ between pumpkin seed extract and placebo. In the case of pumpkin seed (responders: 58.5%), the difference compared with placebo (responders: 47.3%) was descriptively significant. The study products were well tolerated. Overall, in men with BPH, 12 months of treatment with pumpkin seed led to a clinically relevant reduction in IPSS compared with placebo. In order to fully justify a recommendation for the use of pumpkin seed to treat moderate LUTS, these findings need to be substantiated in a confirmatory study or systematic review. 2014 S. Karger AG, Basel

  17. A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism.

    Science.gov (United States)

    Ghaleiha, Ali; Rasa, Soudeh Mohebbi; Nikoo, Mohammadali; Farokhnia, Mehdi; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

    2015-09-30

    To assess the safety and efficacy of pioglitazone added to risperidone in the treatment of irritability in autistic disorder (AD), we conducted this study. In a 10-week, randomized, double-blind, parallel-group, placebo-controlled clinical trial, 44 outpatients of both genders aged 4-12 years with a diagnosis of AD and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale were included. Mean change of ABC-C irritability subscale score as primary outcome, change in other ABC-C subscale scores and partial and complete responses were compared between two groups. Twenty patients completed the trial in each group. Level of reduction and effect of time×treatment interaction in the treatment group were significant for irritability (P=0.03), lethargy/social withdrawal (P=0.04) and hyperactivity/non-compliance (P=0.03) but not for stereotypic behavior and inappropriate speech subscales compared with the placebo group. Vomiting and headache were the most frequent reported side-effects. Results of this preliminary study indicate positive effects of pioglitazone compared with placebo in improving the behavioral symptoms of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

    OpenAIRE

    McGraw, Thomas

    2016-01-01

    Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or ...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Glintborg, D.; Andersen, Mikael; Hagen, C.

    2008-01-01

    OBJECTIVE: Our objective was to investigate the effect of pioglitazone on bone mineral density (BMD) and bone turnover markers in polycystic ovary syndrome (PCOS). DESIGN AND SETTING: We conducted a randomized, placebo-controlled study at an outpatient clinic at a university hospital. PATIENTS......: Thirty premenopausal patients with PCOS and 14 age- and weight-matched healthy females participated. INTERVENTIONS: Pioglitazone (30 mg/d) or placebo was given for 16 wk. MAIN OUTCOME MEASURES: Measurements of BMD [hip (neck and total) and lumbar spine (L2-L4)], bone metabolic parameters [alkaline...... phosphatase (ALP), 25-hydroxyvitamin D, C-telopeptide of type I collagen (ICTP), osteocalcin, and PTH], endocrine profiles (testosterone, estradiol, and insulin), and body composition (waist to hip ratio, body mass index, and whole-body dual-energy x-ray absorptiometry scans) were performed. RESULTS: Patients...

  6. Effects of trans fatty acids on glucose homeostasis: a meta-analysis of randomized, placebo-controlled clinical trials123

    OpenAIRE

    Aronis, Konstantinos N; Khan, Sami M; Mantzoros, Christos S

    2012-01-01

    Background: Although evidence from cohort studies has suggested that trans fatty acid (TFA) consumption may be associated with insulin resistance and diabetes, randomized placebo-controlled trials (RCTs) have yielded conflicting results.

  7. Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial

    NARCIS (Netherlands)

    S. Koning (Sander); L.W.A. van Suijlekom-Smit (Lisette); J.L. Nouwen (Jan); C.M. Verduin (Cees); R.M.D. Bernsen (Roos); A.P. Oranje (Arnold); S. Thomas (Siep); J.C. van der Wouden (Hans)

    2002-01-01

    textabstractOBJECTIVE: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo. DESIGN: Randomised placebo controlled trial. SETTING: General practices in Greater Rotterdam.

  8. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics

    NARCIS (Netherlands)

    Selle, V.; Schalkwijk, S.J.; Vazquez, G.H.; Baldessarini, R.J.

    2014-01-01

    BACKGROUND: Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. METHODS: We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants,

  9. Facilitation of fear extinction in phobic participants with a novel cognitive enhancer: a randomized placebo controlled trial of yohimbine augmentation

    NARCIS (Netherlands)

    Powers, M.B.; Smits, J.A.J.; Otto, M.W.; Sanders, C.; Emmelkamp, P.M.G.

    2009-01-01

    Preliminary animal research suggests that yohimbine hydrochloride, a selective competitive alpha2-adrenergic receptor antagonist, accelerates fear extinction and converts ineffective extinction regimens (long intertrial intervals) to effective ones. This randomized placebo controlled study examined

  10. Misoprostol for cervical priming prior to hysteroscopy in postmenopausal and premenopausal nulliparous women; a multicentre randomised placebo controlled trial

    NARCIS (Netherlands)

    Tasma, M L; Louwerse, M D; Hehenkamp, W J; Geomini, P M; Bongers, M Y; Veersema, S; van Kesteren, P J; Tromp, E; Huirne, J A; Graziosi, G C

    OBJECTIVE: To evaluate the reduction of pain by misoprostol compared with placebo prior to hysteroscopy in postmenopausal and premenopausal nulliparous women. DESIGN: Randomised multicentre double-blind placebo controlled trial. SETTING: Two Dutch teaching hospitals and one Dutch university medical

  11. 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.

  12. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

    OpenAIRE

    Little, A; Levy, R; Chuaqui-Kidd, P; Hand, D

    1985-01-01

    The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improve...

  13. 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...

  14. EFFICACY OF HYOSCINE BUTYLBROMIDE IN TREATMENT OF IRRITABLE BOWEL SYNDROME IN CHILDREN: PLACEBO-CONTROLLED TRIAL

    Directory of Open Access Journals (Sweden)

    K.V. Arifullina

    2008-01-01

    Full Text Available The activity of hyoscine butylbromide (buscopan was evaluated in a placebobcontrolled trial, on pediatric patients with algid type of irritable bowel syndrome. Hyoscine butylbromide favored to the increase of quality of life in pediatric patients, alleviation of clinical symptoms of disease, reliable decrease of malonic dialdehyde and increase of antioxidant activity of blood plasma significantly superior to placebo. Clinical efficacy of hyoscine butylbromide accompanies to its good tolerance and safety.Key words: children, irritable bowel syndrome, hyoscine butylbromide, placebo controlled trial.

  15. "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 (...

  16. A double-blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings.

    Science.gov (United States)

    Mix, Joseph A; Crews, W David

    2002-08-01

    There appears to be an absence of large-scaled clinical trials that have examined the efficacy of Ginkgo biloba extract on the neuropsychological functioning of cognitively intact older adults. The importance of such clinical research appears paramount in light of the plethora of products containing Ginkgo biloba that are currently being widely marketed to predominantly cognitively intact adults with claims of enhanced cognitive performances. The purpose of this research was to conduct the first known, large-scaled clinical trial of the efficacy of Ginkgo biloba extract (EGb 761) on the neuropsychological functioning of cognitively intact older adults. Two hundred and sixty-two community-dwelling volunteers (both male and female) 60 years of age and older, who reported no history of dementia or significant neurocognitive impairments and obtained Mini-Mental State Examination total scores of at least 26, were examined via a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel-group, clinical trial. Participants were randomly assigned to receive either Ginkgo biloba extract EGb 761(n = 131; 180 mg/day) or placebo (n = 131) for 6 weeks. Efficacy measures consisted of participants' raw change in performance scores from pretreatment baseline to those obtained just prior to termination of treatment on the following standardized neuropsychological measures: Selective Reminding Test (SRT), Wechsler Adult Intelligence Scale-III Block Design (WAIS-III BD) and Digit Symbol-Coding (WAIS-III DS) subtests, and the Wechsler Memory Scale-III Faces I (WMS-III FI) and Faces II (WMS-III FII) subtests. A subjective Follow-up Self-report Questionnaire was also administered to participants just prior to termination of the treatment phase. Analyses of covariance indicated that cognitively intact participants who received 180 mg of EGb 761 daily for 6 weeks exhibited significantly more improvement on SRT tasks involving delayed (30 min) free recall (p visual material

  17. A Randomized, Double-Blind, Placebo-Controlled Trial of Eszopiclone for the Treatment of Insomnia in Patients with Chronic Low Back Pain

    Science.gov (United States)

    Goforth, Harold W.; Preud'homme, Xavier A.; Krystal, Andrew D.

    2014-01-01

    Study Objectives: Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. Design: Double-blind, placebo-controlled, parallel-group, 1-mo trial. Setting: Duke University Medical Center Outpatient Sleep Clinic. Patients: Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). Interventions: Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. Measurements and Results: ESZ significantly improved total sleep time (mean increase: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. Conclusions: The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. Trial Registration: clinicaltrials.gov identifier: NCT00365976 Citation: Goforth HW, Preud'homme XA, Krystal AD. A randomized, double-blind, placebo-controlled trial of eszopiclone

  18. 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.

  19. 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

  20. 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.

  1. A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems.

    Science.gov (United States)

    Stocks, Jennifer Dugan; Taneja, Baldeo K; Baroldi, Paolo; Findling, Robert L

    2012-04-01

    To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder (ADHD) and serious conduct problems. This open-label, parallel-group, dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD and persistent, serious conduct problems to receive oral molindone thrice daily for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight conduct problems. Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale-revised (SNAP-IV) ADHD-related subscale scores. The study randomized 78 children; 55 completed the study. Treatment with molindone was generally well tolerated, with no clinically meaningful changes in laboratory or physical examination findings. The most common treatment-related adverse events (AEs) included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs increased with increasing dose. NCBRF-TIQ subscale scores improved in all four treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups 1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all treatment groups, and CGI-I scores improved to the greatest degree in group 4. Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20-40 mg (≥ 30 kg) was well tolerated, and preliminary efficacy results suggest that molindone produces dose-related behavioral improvements over 9-12 weeks. Additional double-blind, placebo-controlled trials are needed to further investigate molindone in this pediatric population.

  2. A randomized, double-blind, placebo-controlled trial of eszopiclone for the treatment of insomnia in patients with chronic low back pain.

    Science.gov (United States)

    Goforth, Harold W; Preud'homme, Xavier A; Krystal, Andrew D

    2014-06-01

    Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. Double-blind, placebo-controlled, parallel-group, 1-mo trial. Duke University Medical Center Outpatient Sleep Clinic. Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP TIME (MEAN INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. clinicaltrials.gov identifier: NCT00365976.

  3. Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Sagheb, Mohammad Mahdi; Dormanesh, Banafshe; Fallahzadeh, Mohammad Kazem; Akbari, Hamideh; Sohrabi Nazari, Sahar; Heydari, Seyed Taghi; Behzadi, Saeed

    2012-05-01

    Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial. Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase. Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1-11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5-4.8), (PVitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements.

    Science.gov (United States)

    Smith, David H; Neutel, Joel M; Lacourcière, Yves; Kempthorne-Rawson, Joan

    2003-07-01

    This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.

  5. Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Fiorelli, Alfonso; Mazzella, Antonio; Passavanti, Beatrice; Sansone, Pasquale; Chiodini, Paolo; Iannotti, Mario; Aurilio, Caterina; Santini, Mario; Pace, Maria Caterina

    2015-09-01

    To evaluate if the pre-emptive administration of ketamine would potentiate the effect of intravenous morphine analgesia in the management of post-thoracotomy pain. This was a unicentre, double-blind, placebo-controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (ketamine group) or an equivalent dose of normal saline (placebo group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen. Primary end-point was the pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma C-reactive protein levels, the morphine consumption and the rate of side effects. The measurements were carried out 6, 12, 24, 36 and 48 hours postoperatively. A total of 75 patients were randomized of whom 38 were allocated to ketamine group and 37 to placebo group. Baseline characteristics were comparable. Ketamine compared with placebo group showed a significant reduction of pain scores (P = 0.01), C-reactive protein (P morphine consumption (P psychological side effects related to the use of ketamine were registered. The administration of ketamine before surgery may be an effective adjunct to intravenous morphine analgesia in acute post-thoracotomy pain management. In ketamine group, satisfaction of pain relief was significantly higher with a significant reduction of inflammatory response and morphine consumption compared with placebo group. Our results, if confirmed by larger studies, may be of clinical relevance in situations where epidural analgesia or other analgesic procedures different from systemic opioid analgesia are unavailable or contraindicated. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study.

    Science.gov (United States)

    2005-02-01

    Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. Multicenter, randomized, placebo-controlled, double-blind, parallel-group study. Parkinson disease patients (N = 472) with at least 21/2 hours of daily "off" (poor motor function) time, despite optimized treatment with other anti-PD medications. Rasagiline, 1.0 or 0.5 mg/d, or matching placebo. Change from baseline in total daily off time measured by patients' home diaries during 26 weeks of treatment, percentage of patients completing 26 weeks of treatment, and adverse event frequency. During the treatment period, the mean adjusted total daily off time decreased from baseline by 1.85 hours (29%) in patients treated with 1.0 mg/d of rasagiline, 1.41 hours (23%) with 0.5 mg/d rasagiline, and 0.91 hour (15%) with placebo. Compared with placebo, patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day, and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day. Prespecified secondary end points also improved during rasagiline treatment, including scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (activities of daily living in the off state and motor performance in the "on" state). Rasagiline was well tolerated. Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients. In light of recently reported benefits in patients with early illness, rasagiline is a promising new treatment for PD.

  7. Effects of lactoferrin and lactoperoxidase-containing food on the oral hygiene status of older individuals: A randomized, double blinded, placebo-controlled clinical trial.

    Science.gov (United States)

    Morita, Yu; Ishikawa, Kentaro; Nakano, Manabu; Wakabayashi, Hiroyuki; Yamauchi, Koji; Abe, Fumiaki; Ooka, Takafumi; Hironaka, Shouji

    2017-05-01

    Lactoferrin and lactoperoxidase have antimicrobial effects against oral pathogens. This randomized, double-blinded, placebo-controlled parallel group study tested the efficacy of a lactoferrin and lactoperoxidase-containing tablet (LF + LPO tablet) in improving the oral hygiene status of older individuals. A total of 46 participants (31 nursing home residents and 15 healthy older individuals) were randomly assigned to receive either lactoferrin and lactoperoxidase-containing tablets or placebo tablets, and were asked to suck on a tablet after every meal for 8 weeks. Oral and bacteriological assessments were carried out at baseline, 4 weeks and 8 weeks. A total of 47 participants (test group n = 20; mean age 80.4 ± 6.4 years; placebo group n = 17; mean age 85.9 ± 6.7 years) were included in the efficacy analysis. In the test group, the total number of bacteria in the tongue coating was significantly reduced at 4 and 8 weeks compared with that at baseline, and the number of Porphyromonas gingivalis and Fusobacterium nucleatum was significantly reduced at 8 weeks. The total number of bacteria and the number of P. gingivalis in the supragingival plaque were significantly reduced at 8 weeks. Furthermore, there was a significant difference in the change in the number of P. gingivalis in supragingival plaque at 8 weeks between the two groups. Lactoferrin and lactoperoxidase-containing tablet ingestion showed antibacterial effects on periodontal bacteria present in the tongue coating and supragingival plaque, indicating that long-term ingestion could improve the oral hygiene of older individuals. Geriatr Gerontol Int 2017; 17: 714-721. © 2016 Japan Geriatrics Society.

  8. The RESPIRE trials: Two phase III, randomized, multicentre, placebo-controlled trials of Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) in non-cystic fibrosis bronchiectasis.

    Science.gov (United States)

    Aksamit, Timothy; Bandel, Tiemo-Joerg; Criollo, Margarita; De Soyza, Anthony; Elborn, J Stuart; Operschall, Elisabeth; Polverino, Eva; Roth, Katrin; Winthrop, Kevin L; Wilson, Robert

    2017-07-01

    The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥2 exacerbations in the previous 12months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5mg or placebo using a pocket-sized inhaler in one of two regimens: 28days on/off treatment or 14days on/off treatment. The treatment period is 48weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. The RESPIRE trials are registered in ClinicalTrials.gov, ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration

  9. Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Costello, John M; Dunbar-Masterson, Carolyn; Allan, Catherine K; Gauvreau, Kimberlee; Newburger, Jane W; McGowan, Francis X; Wessel, David L; Mayer, John E; Salvin, Joshua W; Dionne, Roger E; Laussen, Peter C

    2014-07-01

    We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0-24]; milrinone, 18 [0-23]; placebo, 20 [0-23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. http://www.clinicaltrials.gov. Unique identifier: NCT00543309. © 2014 American Heart Association, Inc.

  10. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rebeccah Slater

    2016-11-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  11. Transversus abdominis plane block reduces morphine consumption in the early postoperative period following microsurgical abdominal tissue breast reconstruction: a double-blind, placebo-controlled, randomized trial.

    Science.gov (United States)

    Zhong, Toni; Ojha, M; Bagher, Shaghayegh; Butler, Kate; Srinivas, Coimbatore; McCluskey, Stuart A; Clarke, Hance; O'Neill, Anne C; Novak, Christine B; Hofer, Stefan O P

    2014-11-01

    The analgesic efficacy of the transversus abdominis plane peripheral nerve block following abdominal tissue breast reconstruction has not been studied in a randomized controlled trial. The authors conducted a double-blind, placebo-controlled, 1:1 allocation, two-arm parallel group, superiority design, randomized controlled trial in patients undergoing microsurgical abdominally based breast reconstruction. Intraoperatively, epidural catheters were inserted under direct vision through the triangle of Petit on both sides of the abdomen into the transversus abdominis plane just before rectus fascial closure. Patients received either bupivacaine (study group) or saline (placebo group) through the catheters for 2 postoperative days. All patients received hydromorphone by means of a patient-controlled analgesic pump. The primary outcome was the difference in the parenteral opioid consumption on each postoperative day between the groups. The secondary outcome measures included the following: total in-hospital opioid; antinausea medication; pain, nausea, and sedation scores; Quality of Recovery Score; time to ambulation; and hospital stay duration. Between September of 2011 and June of 2013, 93 patients were enrolled: 49 received bupivacaine and 44 received saline. There were 11 postoperative complications (13 percent); none were related to the catheter. Primary outcomes were completed by 85 of 93 patients (91.3 percent); the mean parenteral morphine consumption was significantly reduced on postoperative day 1 in the bupivacaine group (20.7±20.1 mg) compared with 30.0±19.1 mg in the control group (p=0.02). There were no significant differences in secondary outcomes. Following abdominally based breast reconstruction, transversus abdominis plane peripheral nerve block is safe and significantly reduces morphine consumption in the early postoperative period. Therapeutic, II.

  12. Evaluation of the glycine transporter inhibitor Org 25935 as augmentation to cognitive-behavioral therapy for panic disorder: a multicenter, randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Nations, Kari R; Smits, Jasper A J; Tolin, David F; Rothbaum, Barbara O; Hofmann, Stefan G; Tart, Candyce D; Lee, Allen; Schipper, Jacques; Sjogren, Magnus; Xue, Dixi; Szegedi, Armin; Otto, Michael W

    2012-05-01

    A growing body of evidence supports the efficacy of D-cycloserine (DCS), a partial agonist at the N-methyl-D-aspartate (NMDA) glutamate receptor, as augmentation to cognitive-behavioral therapy (CBT) in the treatment of anxiety disorders. Org 25935 is a glycine transporter 1 inhibitor that acts to increase synaptic glycine levels and enhance NMDA-mediated glutamatergic activity. The aim of this study was to examine the efficacy of a glutamatergic compound other than DCS in a CBT augmentation paradigm. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial for which participants were recruited from November 2008 through February 2010. Eligible adult patients diagnosed (DSM-IV) with panic disorder with or without agoraphobia (N = 40) were scheduled to receive 5 manualized CBT treatment sessions. Participants were randomly assigned to receive either a dose of Org 25935 (4 mg or 12 mg) or placebo 2 hours prior to the start of CBT sessions 3, 4, and 5. The primary endpoint was symptomatic change as measured by the Panic Disorder Severity Scale (PDSS) 1 week following the last CBT session. Although mean PDSS total scores decreased significantly from baseline to end of treatment in every group, no statistically significant benefit was observed for Org 25935 (4 or 12 mg) over placebo on the primary endpoint or on any secondary efficacy endpoint. Org 25935 showed no safety issues at either dose but was much better tolerated at the 4-mg dose level than at the 12-mg dose level. Org 25935 demonstrated no benefit over placebo in augmenting CBT for panic disorder. Study limitations and implications are discussed. clinicaltrials.gov Identifier: NCT00725725. © Copyright 2012 Physicians Postgraduate Press, Inc.

  13. Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries.

    Science.gov (United States)

    Buvat, Jacques; Tesfaye, Fisseha; Rothman, Margaret; Rivas, David A; Giuliano, François

    2009-04-01

    Dapoxetine is being developed for the on-demand treatment of premature ejaculation (PE). Previous clinical trials have demonstrated its safety and efficacy. To evaluate the long-term efficacy and safety of dapoxetine in men with PE. This randomized, double-blind, parallel-group, placebo-controlled, phase 3 trial, conducted in 22 countries, enrolled men (N=1162) > or = 18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for > or = 6 mo, with an intravaginal ejaculatory latency time (IELT) or = 75% of intercourse episodes at baseline. Dapoxetine 30 mg or dapoxetine 60 mg or placebo on demand (1-3 h before intercourse) for 24 wk. Stopwatch-measured IELT, Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change, adverse events (AEs). The study was completed by 618 men. Mean average IELT increased from 0.9 min at baseline (all groups) to 1.9 min, 3.2 min, and 3.5 min with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively, at study end point; geometric mean IELT increased from 0.7 min at baseline to 1.1 min, 1.8 min, and 2.3 min, respectively, at study end point. All PEP measures and IELTs improved significantly with dapoxetine versus placebo at week 12 and week 24 (p<0.001 for all). The most common AEs were nausea, dizziness, diarrhea, and headache. AEs led to discontinuation in 1.3%, 3.9%, and 8.2% of subjects with placebo and dapoxetine 30 mg and dapoxetine 60 mg, respectively. Limitations of this study included the exclusion of men who were not in long-term monogamous relationships. Dapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population.

  14. [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.

  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. Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Pozzoni, Pietro; Riva, Alessia; Bellatorre, Alessandro Giacco; Amigoni, Maria; Redaelli, Elena; Ronchetti, Anna; Stefani, Mariangela; Tironi, Rosangela; Molteni, Edoardo Ennio; Conte, Dario; Casazza, Giovanni; Colli, Agostino

    2012-06-01

    Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Probiotics were effective in preventing AAD and CDAD in several randomized controlled trials. This study was aimed at testing the effect of Saccharomyces boulardii on the occurrence of AAD and CDAD in hospitalized patients. A single-center, randomized, double-blind, placebo-controlled, parallel-group trial was performed. Patients being prescribed antibiotics or on antibiotic therapy for boulardii or an indistinguishable placebo twice daily within 48 h of beginning antibiotic therapy, continued treatment for 7 days after antibiotic withdrawal, and were followed for 12 weeks after ending antibiotic treatment. Of 562 consecutive eligible patients, 275 patients aged 79.2 ± 9.8 years (134 on placebo) were randomized and 204 aged 78.4 ± 10.0 years (98 on placebo) completed the follow-up. AAD developed in 13.3% (13/98) of the patients receiving placebo and in 15.1% (16/106) of those receiving S. boulardii (odds ratio for S. boulardii vs. placebo, 1.16; 95% confidence interval (CI), 0.53-2.56). Five cases of CDAD occurred, 2 in the placebo group (2.0%) and 3 in the probiotic group (2.8%; odds ratio for S. boulardii vs. placebo, 1.40; 95% CI, 0.23-8.55). There was no difference in mortality rates (12.7% vs. 15.6%, P=0.60). In elderly hospitalized patients, S. boulardii was not effective in preventing the development of AAD.

  17. A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia

    Science.gov (United States)

    Rafii, Michael S.; Skotko, Brian G.; McDonough, Mary Ellen; Pulsifer, Margaret; Evans, Casey; Doran, Eric; Muranevici, Gabriela; Kesslak, Patrick; Abushakra, Susan; Lott, Ira T.

    2018-01-01

    Background ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer’s disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. Objective To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. Methods This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase 2 study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2:1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. Results There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram (ECG) results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. Conclusion Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy. PMID:28453471

  18. A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

    Science.gov (United States)

    Rafii, Michael S; Skotko, Brian G; McDonough, Mary Ellen; Pulsifer, Margaret; Evans, Casey; Doran, Eric; Muranevici, Gabriela; Kesslak, Patrick; Abushakra, Susan; Lott, Ira T

    2017-01-01

    ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.

  19. The Effect of Ginger (Zingiber officinalis and Artichoke (Cynara cardunculus Extract Supplementation on Functional Dyspepsia: A Randomised, Double-Blind, and Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Attilio Giacosa

    2015-01-01

    Full Text Available Objective. Functional dyspepsia (FD is a frequent clinical finding in western world. The aim of this study is to compare the efficacy of a ginger and artichoke supplementation versus placebo in the treatment of FD. Methods. A prospective multicentre, double blind, randomized, placebo controlled, parallel-group comparison of the supplement and placebo over a period of 4 weeks was performed. Two capsules/day were supplied (before lunch and dinner to 126 FD patients (supplementation/placebo: 65/61. Results. After 14 days of treatment, only supplementation group (SG showed a significant amelioration (SG: αS=+1.195 MCA score units (u, P=0.017; placebo: αP=+0.347 u, P=0.513. The intercept (α resulted to be significantly higher in SG than in placebo (αS-αP=+0.848 u, P<0.001. At the end of the study, the advantage of SG versus placebo persists without variation (βS-βP=+0.077 u, P=0.542. In SG, a significant advantage is observed for nausea (βS-βP=-0.398 u, P<0.001, epigastric fullness (βS-βP=-0.241, P<0.001, epigastric pain (βS-βP=-0.173 u, P=0.002, and bloating (βS-βP=-0.167 u, P=0.017. Conclusions. The association between ginger and artichoke leaf extracts appears safe and efficacious in the treatment of FD and could represent a promising treatment for this disease.

  20. 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

  1. A phase III, randomized, multi-center, double blind, placebo controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal.

    Science.gov (United States)

    Gorodetzky, Charles W; Walsh, Sharon L; Martin, Peter R; Saxon, Andrew J; Gullo, Kristen L; Biswas, Kousick

    2017-07-01

    Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal. The primary efficacy measures were SOWS-Gossop on Day 3 and time-to-dropout. Secondary endpoints included the proportion of participants who were completers; area under the 5-day SOWS-Gossop - time curve (i.e., AUC 1-5 ), and daily mean SOWS-Gossop, OOWS-Handelsman, MCGI (subject and rater), and VAS-E scores. Participants received lofexidine HCl 3.2mg daily in four divided doses or matching placebo on Days 1-5, followed by 2days of placebo. Lofexidine significantly decreased mean Day 3 SOWS scores compared to placebo, 6.32 versus 8.67, respectively, p=0.0212. Fewer lofexidine patients were early terminators compared to placebo (59 versus 80, respectively); and non-completers in the lofexidine group remained in the study longer than those assigned to placebo (p=0.0034). Secondary endpoints consistently favored lofexidine. Lofexidine was well tolerated in this trial. Lofexidine significantly decreased SOWS scores compared to placebo and demonstrated better retention rates in participants undergoing opioid withdrawal. Lofexidine potentially offers a useful non-opioid alternative to treat opioid withdrawal symptoms. Copyright © 2017. Published by Elsevier B.V.

  2. 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.

  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. 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...

  5. Randomized clinical trial of transversus abdominis plane block versus placebo control in live-donor nephrectomy.

    Science.gov (United States)

    Hosgood, Sarah A; Thiyagarajan, Umasanker M; Nicholson, Harriet F L; Jeyapalan, Inthira; Nicholson, Michael L

    2012-09-15

    Laparoscopic surgery reduces pain after donor nephrectomy; however, most patients still require a significant amount of postoperative parenteral opiate analgesia. Therefore, there is a need to investigate techniques that might further reduce postoperative pain. This study assessed the safety and efficacy of using a transversus abdominis plane (TAP) block in a randomized, double-blind, placebo-controlled trial. Forty-six patients were analyzed in the trial and were randomized to undergo the TAP block procedure with either bupivacaine (n=24) or saline placebo (Control n=22) injected into the muscle plane. Prefilled syringes were dispensed with the group allocation concealed to maintain blinding. After surgery, the amount of morphine, level of pain, and measures of recovery were recorded. The amount of morphine used 6 hr after surgery was significantly lower in patients receiving TAP block with bupivacaine compared with the control (presented as mean [SD], 12.4 [8.4] vs. 21.2 [14.0] mg; P=0.015). However, the total amount of morphine used was similar in both groups 45.6 [31.4] vs. 52.7 [28.8] mg; P=0.771. Patients in the bupivacaine group experienced significantly less pain on postoperative days 1 (score, 19 [15] vs. 37 [20]; P=0.003) and 2 (score, 11 [10] vs. 19 [13]; P=0.031). Recovery and postoperative hospital stay were similar in both groups. There were no complications associated with the procedure. The TAP block procedure is beneficial in reducing postoperative pain and early morphine requirements in laparoscopic live-donor nephrectomy.

  6. A randomized, placebo-controlled trial of repetitive spinal magnetic stimulation in lumbosacral spondylotic pain.

    Science.gov (United States)

    Lo, Yew L; Fook-Chong, Stephanie; Huerto, Antonio P; George, Jane M

    2011-07-01

    Lumbar spondylosis is a degenerative disorder of the spine, whereby pain is a prominent feature that poses therapeutic challenges even after surgical intervention. There are no randomized, placebo-controlled studies utilizing repetitive spinal magnetic stimulation (SMS) in pain associated with lumbar spondylosis. In this study, we utilize SMS technique for patients with this condition in a pilot clinical trial. We randomized 20 patients into SMS treatment or placebo arms. All patients must have clinical and radiological evidence of lumbar spondylosis. Patients should present with pain in the lumbar region, localized or radiating down the lower limbs in a radicular distribution. SMS was delivered with a Medtronic R30 repetitive magnetic stimulator (Medtronic Corporation, Skovlunde, Denmark) connected to a C-B60 figure of eight coil capable of delivering a maximum output of 2 Tesla per pulse. The coil measured 90 mm in each wing and was centered over the surface landmark corresponding to the cauda equina region. The coil was placed flat over the back with the handle pointing cranially. Each patient on active treatment received 200 trains of five pulses delivered at 10 Hz, at an interval of 5 seconds between each train. "Sham" SMS was delivered with the coil angled vertically and one of the wing edges in contact with the stimulation point. All patients tolerated the procedure well and no side effects of SMS were reported. In the treatment arm, SMS had resulted in significant pain reduction immediately and at Day 4 after treatment (P lumbar spondylosis in a randomized, double-blind, placebo-controlled setting. The novel findings support the potential of this technique for future studies pertaining to neuropathic pain. Wiley Periodicals, Inc.

  7. 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.

  8. A randomized double-blind placebo-controlled clinical trial on efficacy and safety of association of simethicone and Bacillus coagulans (Colinox®) in patients with irritable bowel syndrome.

    Science.gov (United States)

    Urgesi, R; Casale, C; Pistelli, R; Rapaccini, G L; de Vitis, I

    2014-01-01

    Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that affects 15-20% of the Western population. There are currently few therapeutic options available for the treatment of IBS. The aim of this study is to evaluate the efficacy and the safety of a medical device containing a combination of Simethicone and Bacillus coagulans in the treatment of IBS. This is a monocentric double-blind, placebo-controlled parallel group clinical trial. Adult subjects suffering from IBS as defined by Rome III criteria were enrolled. Bloating, discomfort, abdominal pain were assessed as primary end point. Subjects received the active treatment or placebo 3 time a day after each meal for 4 weeks of study period. Subjects were submitted to visit at Day 0 (T1), at Days 14 (T2) and 29 (T3). Fifty-two patients were included into the study. Intragroup analysis showed a significant reduction of the bloating, discomfort and pain in Colinox® group (CG) compared to placebo group (PG). Between group analysis confirmed, at T1-T3, significant differences between CG and PG in bloating and discomfort. Simethicone is an inert antifoaming able to reduce bloating, abdominal discomfort. Literature offers increasing evidence linking alterations in the gastrointestinal microbiota and IBS and it is well known that probiotics are important to restore the native gut microbiota. The Colinox medical device is specifically targeted against most intrusive symptom of IBS (bloating) and it is also able to counteract the most accredited ethiopathogenetic factor in IBS (alterations of intestinal microbiota). This is the first randomized double-blind placebo-controlled clinical trial demonstrating the efficacy and safety of a combination of simethicone and Bacillus coagulans in treatment of IBS.

  9. 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

  10. 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

  11. 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

  12. High-volume infiltration analgesia in total knee arthroplasty: a randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Andersen, L.O.; Husted, H.; Otte, K.S.

    2008-01-01

    with a detailed description of the infiltration technique. METHODS: In a randomized, double-blind, placebo-controlled trial in 12 patients undergoing bilateral knee arthroplasty, saline or high-volume (170 ml) ropivacaine (0.2%) with epinephrine was infiltrated around each knee, with repeated doses administered...

  13. Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; Herpertz, I.; Pasker, L.; van der Heide, S.; Kukler, J.; Jansink, C.; Vaessen, W.; Beusekamp, B. J.; Dubois, A. E. J.

    P>Background: In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of

  14. Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; Herpertz, I.; Pasker, L.; van der Heide, S.; Kukler, J.; Jansink, C.; Vaessen, W.; Beusekamp, B. J.; Dubois, A. E. J.

    2011-01-01

    In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for

  15. Topical glyceryl trinitrate treatment of chronic patellar tendinopathy : a randomised, double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam

    Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN

  16. OVULATION INDUCTION IN PREMATURE OVARIAN FAILURE - A PLACEBO-CONTROLLED RANDOMIZED TRIAL COMBINING PITUITARY SUPPRESSION WITH GONADOTROPIN STIMULATION

    NARCIS (Netherlands)

    VANKASTEREN, YM; HOEK, A; SCHOEMAKER, J

    Objectives: To determine the effect of pituitary suppression with a GnRH agonist (GnRH-a) on the success of ovulation induction with exogenous gonadotropins in patients with premature ovarian failure (POF). Design: Placebo-controlled, randomized, double-blind study. The data were analyzed with a

  17. 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

  18. Cognitive, health and psychosocial effects of melatonin and light therapy in childhood insomnia. Double-blind placebo-controlled study

    NARCIS (Netherlands)

    Smits, M.; van Maanen, A.; Meijer, A.M.; van der Heijden, K.; Oort, F.

    2017-01-01

    Introduction: To examine effects of melatonin and light therapy on cognitive, health and psychosocial outcomes in children with chronic sleep onset insomnia; and to disentangle direct effects from indirect effects through sleep improvement. Methods: A randomized, double-blind placebo-controlled

  19. 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

  20. Masking foods for food challenge: practical aspects of masking foods for a double-blind, placebo-controlled food challenge

    NARCIS (Netherlands)

    Huijbers, G. B.; Colen, A. A.; Jansen, J. J.; Kardinaal, A. F.; Vlieg-Boerstra, B. J.; Martens, B. P.

    1994-01-01

    In diagnosing a food allergy or food intolerance, a double-blind, placebo-controlled food challenge (DBPCFC) with the suspected food or food substance is the only method available for objective confirmation of an assumed relationship between a suspected agent and a complaint. When the use of

  1. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results

    DEFF Research Database (Denmark)

    Pastorello, Elide A; Vieths, Stefan; Pravettoni, Valerio

    2002-01-01

    The hazelnut major allergens identified to date are an 18-kd protein homologous to Bet v 1 and a 14-kd allergen homologous to Bet v 2. No studies have reported hazelnut allergens recognized in patients with positive double-blind, placebo-controlled food challenge (DBPCFC) results or in patients...

  2. 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...

  3. 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

  4. 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

  5. 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...

  6. Implant decontamination during surgical peri-implantitis treatment : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    de Waal, Yvonne C. M.; Raghoebar, Gerry M.; Huddleston Slater, James J. R.; Meijer, Henny J. A.; Winkel, Edwin G.; van Winkelhoff, Arie Jan

    Aim The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. Material & Methods Thirty patients (79 implants) with

  7. Implant decontamination during surgical peri-implantitis treatment : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    de Waal, Yvonne C.M.; Raghoebar, Gerry M; Huddleston Slater, James J R; Meijer, Hendrikus; Winkel, Edwin G; van Winkelhoff, Arie Jan

    AIM: The objective of this randomized, double-blind, placebo-controlled trial was to study the effect of implant surface decontamination with chlorhexidine (CHX)/cetylpyridinium chloride (CPC) on microbiological and clinical parameters. MATERIAL & METHODS: Thirty patients (79 implants) with

  8. Prospective double blind randomized placebo-controlled clinical trial of the pectoral nerves (Pecs) block type II

    NARCIS (Netherlands)

    Versyck, B.; Geffen, G.J. van; Houwe, P. Van

    2017-01-01

    STUDY OBJECTIVE: The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves (Pecs) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery. DESIGN: A prospective randomized double blind placebo-controlled study. SETTING:

  9. A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children

    OpenAIRE

    Kambiz Eftekhari; Zahra Vahedi; Mojtaba Kamali Aghdam; Diana Noemi Diaz

    2015-01-01

    Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to ...

  10. Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Vlieg-Boerstra, BJ; Bijleveld, CMA; van der Heide, S; Beusekamp, BJ; Wolt-Plompen, SAA; Kukler, J; Brinkman, J; Duiverman, EJ; Dubois, AEJ

    Background: The use of double-blind, placebo-controlled food challenges (DBPCFCs) is considered the gold standard for the diagnosis of food allergy. Despite this, materials and methods used in DBPCFCs have not been standardized. Objective: The purpose of this study was to develop and validate

  11. 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

  12. Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial

    NARCIS (Netherlands)

    Padberg, M.; de Bruijn, S. F. T. M.; de Haan, R. J.; Tavy, D. L. J.

    2004-01-01

    Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum

  13. 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

  14. 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

  15. The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Gentile, Pietro; Garcovich, Simone; Bielli, Alessandra; Scioli, Maria Giovanna; Orlandi, Augusto; Cervelli, Valerio

    2015-11-01

    Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, we report the results of a randomized, evaluator-blinded, placebo-controlled, half-head group study to compare, with the aid of computerized trichograms, hair regrowth with PRP versus placebo. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. PRP, prepared from a small volume of blood, was injected on half of the selected patients' scalps with pattern hair loss. The other half was treated with placebo. Three treatments were administered to each patient at 30-day intervals. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki67 evaluation. Patients were followed for 2 years. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area, and a mean increase in total hair density of 45.9 hairs per cm² compared with baseline values. No side effects were noted during treatment. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles 2 weeks after the last PRP treatment compared with baseline value (p plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, the results of a randomized, placebo-controlled, half-head group study to compare the hair regrowth with PRP versus placebo are reported. Hair regrowth was quantified by a blinded evaluator using computerized trichograms. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical

  16. Influence of oxytocin on emotion recognition from body language: A randomized placebo-controlled trial.

    Science.gov (United States)

    Bernaerts, Sylvie; Berra, Emmely; Wenderoth, Nicole; Alaerts, Kaat

    2016-10-01

    The neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. One mechanism by which OT is hypothesized to promote prosocial behavior is by enhancing the processing of socially relevant information from the environment. With the present study, we explored to what extent OT can alter the 'reading' of emotional body language as presented by impoverished biological motion point light displays (PLDs). To do so, a double-blind between-subjects randomized placebo-controlled trial was conducted, assessing performance on a bodily emotion recognition task in healthy adult males before and after a single-dose of intranasal OT (24 IU). Overall, a single-dose of OT administration had a significant effect of medium size on emotion recognition from body language. OT-induced improvements in emotion recognition were not differentially modulated by the emotional valence of the presented stimuli (positive versus negative) and also, the overall tendency to label an observed emotional state as 'happy' (positive) or 'angry' (negative) was not modified by the administration of OT. Albeit moderate, the present findings of OT-induced improvements in bodily emotion recognition from whole-body PLD provide further support for a link between OT and the processing of socio-communicative cues originating from the body of others. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

    Science.gov (United States)

    Dannon, P N; Sasson, Y; Hirschmann, S; Iancu, I; Grunhaus, L J; Zohar, J

    2000-05-01

    To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

  18. 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.

  19. 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...

  20. Sweeten, soother and swaddle for retinopathy of prematurity screening: a randomised placebo controlled trial.

    LENUS (Irish Health Repository)

    O'Sullivan, A

    2012-02-01

    OBJECTIVE: To assess the efficacy of oral sucrose combined with swaddling and non-nutritive suck (NNS) as a method for reducing pain associated with retinopathy of prematurity (ROP) screening. DESIGN: Randomised placebo controlled study. SETTING: Tertiary level neonatal intensive care unit. SAMPLE: 40 infants undergoing primary eye examination for ROP screening. INTERVENTION: The control group were swaddled, and received 0.2 ml of sterile water given by mouth using a syringe and a soother. The intervention group were swaddled, and received 0.2 ml of sucrose 24% given by mouth using a syringe and a soother. RESULTS: 40 infants were included in the study. There was no difference in mean gestational age at birth, mean birth weight or corrected gestational age at first examination between both groups. The sucrose group had a significantly lower median Neonatal Pain, Agitation and Sedation Scale (N-PASS) score during ROP screening, initially following insertion of the speculum (6.5 vs 5, p=0.02) and subsequently during scleral indentation (9.5 vs 7.5, p=0.03). Fewer infants experienced episodes of desaturations or bradycardia in the intervention group (1 vs 4, p=0.18). CONCLUSION: ROP screening is a necessary but recognised painful procedure. Sucrose combined with NNS and swaddling reduced the behavioural and physiological pain responses. However, pain scores remained consistently high and appropriate pain relief for ROP screening remains a challenge.

  1. 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.

  2. Recruitment and accrual of women in a placebo-controlled clinical pilot study on manual therapy.

    Science.gov (United States)

    Cambron, Jerrilyn A; Hawk, Cheryl; Evans, Roni; Long, Cynthia R

    2004-06-01

    To investigate the accrual rates and recruitment processes among 3 Midwestern sites during a pilot study on manual therapy for chronic pelvic pain. Multisite pilot study for a randomized, placebo-controlled clinical trial. Three chiropractic institutions in or near major metropolitan cities in the Midwestern United States. Thirty-nine women aged 18 to 45 with chronic pelvic pain of at least 6 months duration, diagnosed by a board certified gynecologist. The method of recruitment was collected for each individual who responded to an advertisement and completed an interviewer-administered telephone screen. Participants who were willing and eligible after 3 baseline visits were entered into a randomized clinical trial. The number of responses and accrual rates were determined for the overall study, each of the 3 treatment sites, and each of the 5 recruitment efforts. In this study, 355 women were screened over the telephone and 39 were randomized, making the rate of randomization approximately 10%. The most effective recruitment methods leading to randomization were direct mail (38%) and radio advertisements (34%). However, success of the recruitment process differed by site. Based on the accrual of this multisite pilot study, a full-scale trial would not be feasible using this study's parameters. However, useful information was gained on recruitment effectiveness, eligibility criteria, and screening protocols among the 3 metropolitan sites.

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

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    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.

  4. 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

  5. Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers

    Directory of Open Access Journals (Sweden)

    E. Tiralongo

    2012-01-01

    Full Text Available Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P<0.0005. However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P=0.05 during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.

  6. 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

  7. 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.

  8. 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.

  9. Topical undecylenic acid for herpes simplex labialis: a multicenter, placebo-controlled trial.

    Science.gov (United States)

    Shafran, S D; Sacks, S L; Aoki, F Y; Tyrrell, D L; Schlech, W F; Mendelson, J; Rosenthal, D; Gill, M J; Bader, R L; Chang, I

    1997-07-01

    A multicenter, patient-initiated, double-blind, placebo-controlled trial of 15% undecylenic acid cream was conducted with 573 patients with recurrent herpes labialis. Treatment was applied 5 or 6 times daily until crusting and then thrice daily until healing. Patients were assessed daily until 48 h after crusting and then every other day until healing. Undecylenic acid significantly reduced the incidence and duration of viral shedding and the duration and severity of itching but did not increase abortive episodes or reduce times to healing, crusting, or progression of lesion size. When treatment was initiated during the prodrome, the time to crusting was reduced (P = .02) and the area under the symptom-time curve for pain and tenderness was reduced, approaching statistical significance (P = .06). Active treatment was well tolerated but caused dysgeusia and local irritation. Undecylenic acid 15% cream reduces viral shedding in recurrent herpes labialis, but clinical benefits are minimal and largely restricted to patients initiating therapy during the prodrome.

  10. 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.

  11. 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.

  12. 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.

  13. Prophylaxis of irradiation-induced Diarrhea with smectite. Results of a placebo-controlled investigation

    International Nuclear Information System (INIS)

    Hombrink, J.; Froehlich, D.; Glatzel, M.; Krauss, A.; Thiel, H.J.; Meier, J.; Hamann, D.; Muecke, R.; Glaser, F.H.; Koest, S.

    2000-01-01

    Between April 1994 and May 1995, a total of 176 patients obtaining radiotherapy of the pelvis or the abdomen were evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (=Colina trademark ) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2x6 g smectite daily and 91 patients received 2x6 g placebo. The primary end point of the analysis was the time to the first appearance of diarrhea (≥3 pappy stools). Results: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume ≤837.5 ml, the other with a small bowel volume >837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea). This benefit was statistically not significant. Conclusion: Prophylactic application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance could not be verified neither in the total study group nor in the post-hoc subgroup analysis. (orig.) [de

  14. 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.

  15. The efficacy of azithromycin in pityriasis rosea: A randomized, double-blind, placebo-controlled trial

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    Deepika Pandhi

    2014-01-01

    Full Text Available Background: Macrolides are prescribed in the treatment of pityriasis rosea despite conflicting results of the limited number of studies evaluating their role in its treatment. Aim: A randomized double-blind placebo-controlled trial was conducted to evaluate the effect of azithromycin on the clinical course of pityriasis rosea. Methods: Seventy patients of pityriasis rosea were given either azithromycin (n = 35 or placebo (n = 35 and were followed-up at 2, 4 and 6 weeks. Pruritus was assessed in both groups using the visual analogue scale (VAS . Change in the pityriasis rosea severity score (PRSS and in the VAS were recorded as outcome measures and were compared statistically. Results: The decrease in PRSS from baseline through 2, 4 and 6 weeks within both treatment (P < 0.001 and placebo (P < 0.001 arms was found to be statistically significant; however, this change was not significantly different in the two groups (P = 0.179. Similarly, the decrease in VAS was found to be statistically significant within both groups (P < 0.001; however, the change was comparable between the two groups (P < 0.937. Analysis by Fisher′s exact test did not find a significant difference between the two groups for PRSS and VAS. Conclusion: Azithromycin is not effective in pityriasis rosea and the use of macrolides for this disease should not be encouraged in clinical practice.

  16. 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.

  17. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

    Science.gov (United States)

    Kluckow, Martin; Jeffery, Michele; Gill, Andy; Evans, Nick

    2014-03-01

    Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. Multicentre, double-blind, placebo-controlled randomised trial. Three neonatal intensive care units in Australia. Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. Death or abnormal cranial ultrasound. The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

  18. 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.

  19. 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.

  20. 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.

  1. Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Samir K Gupta

    Full Text Available Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.The difference in mean absolute change (SD in FMD after 8 weeks between the placebo [-1.06 (1.45%] and PTX [-1.93 (3.03%] groups was not significant (P = 0.44. No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI [-83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.ClinicalTrials.gov NCT00796822.

  2. 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

  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. Cyproheptadine in the treatment of autistic disorder: a double-blind placebo-controlled trial.

    Science.gov (United States)

    Akhondzadeh, S; Erfani, S; Mohammadi, M R; Tehrani-Doost, M; Amini, H; Gudarzi, S S; Yasamy, M T

    2004-04-01

    Autism is a childhood-onset disorder of unknown, possibly of multiple aetiologies. The core symptoms of autism are abnormalities in social interaction, communication and behaviour. The involvement of neurotransmitters such as 5-HT has been suggested in neuropsychiatric disorders and particularly in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism. Therefore, it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder. In this 8-week double-blind, placebo-controlled trial, we assessed the effects of cyproheptadine plus haloperidol in the treatment of autistic disorder. Children between the ages 3 and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children at Roozbeh Psychiatric Teaching Hospital were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to cyproheptadine + haloperidol (Group A) or haloperidol + placebo (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of haloperidol and cyproheptadine was titrated up to 0.05 and 0.2 mg/kg/day respectively. Patients were assessed by a third-year resident of psychiatry at baseline and after 2, 4, 6 and 8 weeks of starting medication. The primary measure of the outcome was the Aberrant Behaviour Checklist-Community (ABC-C) and the secondary measure of the outcome was the Childhood Autism Rating Scale (relating to people and verbal communication). Side effects and extrapyramidal symptoms were systematically recorded throughout the study and were assessed using a checklist and the Extrapyramidal Symptoms Rating Scale, administered by a resident of psychiatry during weeks 1, 2, 4, 6 and 8. The ABC-C and the Childhood Autism Rating Scale scores improved

  5. A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial.

    Science.gov (United States)

    Cornu, Catherine; Remontet, Laurent; Noel-Baron, Florence; Nicolas, Alain; Feugier-Favier, Nathalie; Roy, Pascal; Claustrat, Bruno; Saadatian-Elahi, Mitra; Kassaï, Behrouz

    2010-06-22

    To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders. Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group) or olive oil (placebo group) for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i) perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii) sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii) night melatonin and 6 sulfatoxymelatonin (aMT6S) urine rates in a subsample of subjects. The average of Leeds score was similar in both groups (p = 0.95). A marked improvement in the quality of sleep was observed in both placebo (62%) and active (65%) group (p = 0.52). The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91). The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. clinical trials.gov:NCT00484497.

  6. A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Claustrat Bruno

    2010-06-01

    Full Text Available Abstract Background To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ in subjects with moderate to severe sleep disorders. Methods Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group or olive oil (placebo group for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii night melatonin and 6 sulfatoxymelatonin (aMT6S urine rates in a subsample of subjects. Results The average of Leeds score was similar in both groups (p = 0.95. A marked improvement in the quality of sleep was observed in both placebo (62% and active (65% group (p = 0.52. The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91. Conclusions The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. Trial registration: clinical trials.gov:NCT00484497

  7. Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial.

    Science.gov (United States)

    McGraw, Thomas

    2016-01-01

    To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation. The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or placebo solution for 14 days. The study comprised a screening period (visit 1), endoscopy procedure (visits 2 and 3), and followup telephone calls 30 days post-treatment. Safety end points included adverse events (AEs), clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions. A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment) or visit 3 (after treatment). Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo - nonsignificant difference of -7.5% (95% CI: -21.3, 6.3) between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because of an AE. PEG 3350 ASC is safe and well tolerated in patients with functional constipation (NCT01885104).

  8. 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.

  9. 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.

  10. Rasagiline for mild cognitive impairment in Parkinson's disease: A placebo-controlled trial.

    Science.gov (United States)

    Weintraub, Daniel; Hauser, Robert A; Elm, Jordan J; Pagan, Fernando; Davis, Matthew D; Choudhry, Azhar

    2016-05-01

    This study's aims were to determine the efficacy and tolerability of rasagiline, a selective monoamine oxidase inhibitor B, for PD patients with mild cognitive impairment. Patients on stable dopaminergic therapy were randomized to adjunct rasagiline 1 mg/day or placebo in this 24-week, double-blind, placebo-controlled, multisite study. The primary endpoint was mean change from baseline to week 24 on the Scales for Outcomes of Parkinson's Disease-Cognition total score. Key secondary measures included changes in cognition, activities of daily living, motor scores, and Clinical Global Impression of Change, as well as safety and tolerability measures. Of the 170 patients randomized, 151 (88.2%) completed the study. Change in Scales for Outcomes of Parkinson's Disease-Cognition scores were not significantly different in the rasagiline and placebo groups (adjusted mean: 1.6 [standard error {SE} = 0.5] vs. 0.8 [SE = 0.5] points; LS means difference = 0.8; 95% confidence interval: -0.48, 2.05; P = 0.22). There were no between-group differences in change in the MoCA (p=0.84) or Penn Daily Activities Questionnaire (P = 0.48) scores or in the distribution of Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change modified for mild cognitive impairment (P = 0.1). Changes in motor (UPDRS part III; P = 0.02) and activities of daily living (UPDRS part II; P rasagiline. Rasagiline was well tolerated; the most common adverse events in both groups were falls and dizziness. Rasagiline treatment in PD patients with mild cognitive impairment was not associated with cognitive improvement. Rasagiline did not worsen cognition, improved motor symptoms and activities of daily living, and was well tolerated in elderly cognitively impaired patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  11. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.

    Science.gov (United States)

    Kennedy, Stephen B; Bolay, Fatorma; Kieh, Mark; Grandits, Greg; Badio, Moses; Ballou, Ripley; Eckes, Risa; Feinberg, Mark; Follmann, Dean; Grund, Birgit; Gupta, Swati; Hensley, Lisa; Higgs, Elizabeth; Janosko, Krisztina; Johnson, Melvin; Kateh, Francis; Logue, James; Marchand, Jonathan; Monath, Thomas; Nason, Martha; Nyenswah, Tolbert; Roman, François; Stavale, Eric; Wolfson, Julian; Neaton, James D; Lane, H Clifford

    2017-10-12

    The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (PLiberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).

  12. A randomized, placebo-controlled, preoperative trial of allopurinol in subjects with colorectal adenoma.

    Science.gov (United States)

    Puntoni, Matteo; Branchi, Daniela; Argusti, Alessandra; Zanardi, Silvia; Crosta, Cristiano; Meroni, Emanuele; Munizzi, Francesco; Michetti, Paolo; Coccia, Gianni; De Roberto, Giuseppe; Bandelloni, Roberto; Turbino, Laura; Minetti, Egle; Mori, Marco; Salvi, Sandra; Boccardo, Simona; Gatteschi, Beatrice; Benelli, Roberto; Sonzogni, Angelica; DeCensi, Andrea

    2013-02-01

    Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.

  13. 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.

  14. Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder.

    Science.gov (United States)

    Rezaei, Vala; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Sahraian, Ali; Tabrizi, Mina; Rezazadeh, Shams-Ali; Akhondzadeh, Shahin

    2010-10-01

    Autism is a complex neurodevelopmental disorder that forms part of a spectrum of related disorders referred to as Autism Spectrum Disorders. The present study assessed the effects of topiramate plus risperidone in the treatment of autistic disorder. Forty children between the ages of 4 and 12 years with a DSM IV clinical diagnosis of autism who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to topiramate+risperidone (Group A) or placebo+risperidone (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of topiramate was titrated up to 200 mg/day depending on weight (100 mg/day for 30 kg). Patients were assessed at baseline and after 2, 4, 6 and 8 weeks after starting medication. Measure of outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Difference between the two protocols was significant as the group that received topiramate had a greater reduction in ABC-C subscale scores for irritability, stereotypic behavior and hyperactivity/noncompliance. The results suggest that the combination of topiramate with risperidone may be superior to risperidone monotherapy for children with autistic disorder. However the results need to be further confirmed by a larger randomized controlled trial. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. 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.

  16. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Wejse, Christian; Gomes, Victor F; Rabna, Paulo; Gustafson, Per; Aaby, Peter; Lisse, Ida M; Andersen, Paul L; Glerup, Henning; Sodemann, Morten

    2009-05-01

    Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. We conducted a randomized, double-blind, placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at 1 year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).

  17. Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Levin, Frances R; Mariani, John J; Pavlicova, Martina; Brooks, Daniel; Glass, Andrew; Mahony, Amy; Nunes, Edward V; Bisaga, Adam; Dakwar, Elias; Carpenter, Kenneth M; Sullivan, Maria A; Choi, Jean C

    2016-02-01

    Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder. Published by Elsevier Ireland Ltd.

  18. Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial.

    Science.gov (United States)

    Furyk, Jeremy S; Chu, Kevin; Banks, Colin; Greenslade, Jaimi; Keijzers, Gerben; Thom, Ogilvie; Torpie, Tom; Dux, Carl; Narula, Rajan

    2016-01-01

    We assess the efficacy and safety of tamsulosin compared with placebo as medical expulsive therapy in patients with distal ureteric stones less than or equal to 10 mm in diameter. This was a randomized, double-blind, placebo-controlled, multicenter trial of adult participants with calculus on computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28 days and time to stone expulsion. There were 403 patients randomized, 81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95% confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95% confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was no difference in urologic interventions, time to self-reported stone passage, pain, or analgesia requirements. Adverse events were generally mild and did not differ between groups. We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  19. Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

    2018-05-01

    To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. 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.

  1. Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism.

    Science.gov (United States)

    Kahaly, George J; Riedl, Michaela; König, Jochem; Diana, Tanja; Schomburg, Lutz

    2017-11-01

    Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Evaluate efficacy of add-on Se on medical treatment in GD. Double-blind, placebo-controlled, randomized supplementation trial. Academic endocrine outpatient clinic. Seventy untreated hyperthyroid patients with GD. Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Response rate (week 24), recurrence rate (week 36), and safety. A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24 [odds ratio (OR) 0.93; 95% confidence interval (CI), 0.26 to 3.25; P = 0.904] in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13; 95% CI, 0.29 to 2.66; P = 0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85; 95% CI, 0.31 to 2.32; P = 0.80). Serum levels of free triiodothyronine/free tetraiodothyronine, thyroid-stimulating hormone receptor antibody, prevalence of moderate to severe Graves orbitopathy, thyroid volume, and MMI starting dose were significantly lower in responders than in nonresponders. A total of 56 and 63 adverse events occurred in the Se and placebo groups, respectively (P = 0.164), whereas only one drug-related side effect (2.9%) was noted in 35 patients on placebo + MMI. Supplemental Se did not affect response or recurrence rates in GD. Copyright © 2017 Endocrine Society

  2. 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.

  3. 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.

  4. 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.

  5. Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence.

    Science.gov (United States)

    Manzardo, Ann M; He, Jianghua; Poje, Albert; Penick, Elizabeth C; Campbell, Jan; Butler, Merlin G

    2013-12-01

    Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analog, benfotiamine (BF), and BF's effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria for current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, -611 ± 380 standard drinks; PL: N=11, -159 ± 562 standard drinks, p-value=0.02). BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Randomized, placebo-controlled, double-blind trial of Swedish snus for smoking reduction and cessation

    Directory of Open Access Journals (Sweden)

    Nilsson Robert

    2011-09-01

    Full Text Available Abstract Background Epidemiological studies suggest that smokeless tobacco in the form of Swedish snus has been used by many smokers in Scandinavia to quit smoking, but the efficacy of snus has so far not been evaluated in controlled clinical trials. Methods We conducted a randomized, double-blind, placebo-controlled, clinical trial aimed at assessing the efficacy of snus to help adult cigarette smokers in Serbia to substantially reduce, and, eventually, completely stop smoking. The study enrolled 319 healthy smokers aged 20-65 years at two occupational health centers in Belgrade, Serbia. Most of them (81% expressed an interest to quit rather than just reduce their smoking. Study products were used ad libitum throughout the 48-week study period. The main study objective during the first 24 weeks was smoking reduction. The primary end-point was defined as a biologically verified reduction of ≥ 50% in the average number of smoked cigarettes per day during week 21-24 compared to baseline. During week 25-48 participants were actively instructed to stop smoking completely. Outcome measures of biologically verified, complete smoking cessation included 1-week point prevalence rates at clinical visits after 12, 24, 36, and 48 weeks, as well as 4-, 12- and 24-week continued cessation rates at the week 36 and 48 visits. Results At the week 24 visit, the proportion of participants who achieved the protocol definition of a ≥ 50% smoking reduction was similar in the two treatment groups. However, the proportion that reported more extreme reductions (≥ 75% was statistically significantly higher in the snus group than in the placebo group (p Conclusions Swedish snus could promote smoking cessation among smokers in Serbia, that is, in a cultural setting without traditional use of oral, smokeless tobacco. Trial registration www.clinicaltrials.gov, identifier: NCT00601042

  7. Randomized, double-blind, placebo-controlled trial of herbal therapy for children with asthma.

    Science.gov (United States)

    Wong, Eliza L Y; Sung, Rita Yn Tz; Leung, Ting Fan; Wong, Yeuk Oi; Li, Albert M C; Cheung, Kam Lau; Wong, Chun Kwok; Fok, Tai Fai; Leung, Ping Chung

    2009-10-01

    The purpose of this trial was to evaluate whether the herbal formula of CUF2 used as complementary therapy improves the clinical symptoms and biochemical markers in children with asthma using inhaled corticosteroids. In a double-blind, placebo-controlled prospective trial, 85 children with asthma aged 7-15 years were randomly assigned to receive either a daily oral herbal formula of 0.619-g CUF2 capsule of dried aqueous extract with an equal weight of five herbs (Astragalus mongholius Bunge, Cordyceps sinensis Sacc., Radix stemonae, Bulbus fritillariae cirrhosae, and Radix scutellariae) or placebo for 6 months. The primary endpoint was the change in steroids dosage; the secondary outcomes included the disease severity score, lung function test, and biochemical markers in blood. Eighty-five (85) children (42 on active treatment and 43 on placebo) completed the 6-month clinical trial. Children randomized to the herbal formula of CUF2 and the placebo showed a similar improvement in clinical symptoms and biomedical markers. The comparison between the CUF2 group and the placebo group showed no significant difference on the dosage of steroids (-2.3 versus -3.1 mg, p = 0.915), disease severity score (-2.3 versus -3.1, p = 0.215), and lung function test of forced expiratory volume in 1 second/forced vital capacity percent (0.1 versus 0.6%, p = 0.809) and peak expiratory flow rate (-7.3 versus -0.6 l/minutes, p = 0.118). No significant difference was found between the two study groups in the biochemical outcomes measured. The intervention effect of CUF2 was smaller than the placebo effect. This study provides no evidence to support the use of the herbal formula of CUF2 in children with asthma. Parents are thus advised to discuss with health professionals before choosing an herbal formula in preference to conventional treatment modes.

  8. 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.

  9. 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.

  10. Efficacy of physiotherapy management of knee joint osteoarthritis: a randomised, double blind, placebo controlled trial

    Science.gov (United States)

    Bennell, K; Hinman, R; Metcalf, B; Buchbinder, R; McConnell, J; McColl, G; Green, S; Crossley, K

    2005-01-01

    Objective: To determine whether a multimodal physiotherapy programme including taping, exercises, and massage is effective for knee osteoarthritis, and if benefits can be maintained with self management. Methods: Randomised, double blind, placebo controlled trial; 140 community volunteers with knee osteoarthritis participated and 119 completed the trial. Physiotherapy and placebo interventions were applied by 10 physiotherapists in private practices for 12 weeks. Physiotherapy included exercise, massage, taping, and mobilisation, followed by 12 weeks of self management. Placebo was sham ultrasound and light application of a non-therapeutic gel, followed by no treatment. Primary outcomes were pain measured by visual analogue scale and patient global change. Secondary measures included WOMAC, knee pain scale, SF-36, assessment of quality of life index, quadriceps strength, and balance test. Results: Using an intention to treat analysis, physiotherapy and placebo groups showed similar pain reductions at 12 weeks: –2.2 cm (95% CI, –2.6 to –1.7) and –2.0 cm (–2.5 to –1.5), respectively. At 24 weeks, pain remained reduced from baseline in both groups: –2.1 (–2.6 to –1.6) and –1.6 (–2.2 to –1.0), respectively. Global improvement was reported by 70% of physiotherapy participants (51/73) at 12 weeks and by 59% (43/73) at 24 weeks. Similarly, global improvement was reported by 72% of placebo participants (48/67) at 12 weeks and by 49% (33/67) at 24 weeks (all p>0.05). Conclusions: The physiotherapy programme tested in this trial was no more effective than regular contact with a therapist at reducing pain and disability. PMID:15897310

  11. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

    Science.gov (United States)

    Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S.

    2011-01-01

    Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale–cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. PMID:21795660

  12. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model.

    Directory of Open Access Journals (Sweden)

    Paul Walsh

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2 which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase.We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected.We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed.One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (p<0.01 and weight gain (p = 0.08 seemed better in the ibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen.Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes

  13. Femicomfort in the Treatment of Premenstrual Syndromes: A Double-Blind, Randomized and Placebo Controlled Trial

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2010-06-01

    Full Text Available "nObjective:Premenstrual syndromes (PMS affecting 20-40% of women of reproductive age. The aim of this double blind and placebo controlled trial was to investigate whether femicofort a supplement contains Vitamin B6, Vitamin E and evening primrose oil could relieve symptoms of PMS. "nMethod: This was a randomized and double blind clinical trial. The trial was conducted between November 2009 and April March 2010. Women aged 20 to 45 years with regular menstrual cycles and experience of PMS symptoms (According to the current diagnostic criteria proposed by the American College of Obstetrics and Gynecology for at least 6 months were eligible for the study. Patients were randomized to receive femicomfort or placebo in a 1: ratio using a computer-generated code. The assignments were kept in sealed, opaque envelopes until the point of analysis of data. In this double-blind, patients were randomly assigned to receive capsule of femicomfort (Group A or capsule placebo for two menstrual cycles (cycles 3 and 4. The primary outcome measure was the Daily Symptom Report, a checklist of 17 premenstrual symptoms rated from 0 to 4 according to their severity throughout the menstrual cycle. Secondary outcome measure was Hamilton Depression Rating Scale (17-item. "nResults:Femicomfort at this dose was found to be effective in relieving symptoms of PMS. The difference between the femicomfort and placebo in the frequency of side effects was not significant. Conclusion: The results of this study indicate the efficacy of femicomfort in the treatment of PMS.

  14. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model

    Science.gov (United States)

    Walsh, Paul; Behrens, Nicole; Carvallo Chaigneau, Francisco R.; McEligot, Heather; Agrawal, Karan; Newman, John W.; Anderson, Mark; Gershwin, Laurel J.

    2016-01-01

    Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase. Hypotheses We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected. Methods We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (pibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung

  15. The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial--study protocol.

    Science.gov (United States)

    Lee, Dong-Hyo; Seo, Eun-Sung; Hong, Jin-Tae; Lee, Gang-Tai; You, Young-Kyoung; Lee, Kun-Kook; Jo, Ga-Won; Kim, Nam-Kwen

    2013-11-25

    Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition.This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ health-related quality of life

  16. The efficacy and safety of a proposed herbal moisturising cream for dry skin and itch relief: a randomised, double-blind, placebo-controlled trial- study protocol

    Science.gov (United States)

    2013-01-01

    Background Moisturisers prevent and treat dry skin. They can also protect sensitive skin, improve skin tone and texture, and mask imperfections. Herbal medicines or their extracts have been available as topical formulations and cosmetics. Arctium lappa L. (Asteraceae) has been used to treat inflammatory disorders and various skin problems. It could be a candidate herbal medicine for treating dry skin condition. This study aims to establish the efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract, which has been approved by the Korean Ministry of Food and Drug Safety for use in cosmetics. Methods/Designs This study is a randomised, double-blind, placebo-controlled study with two parallel groups (proposed herbal moisturising cream vs. placebo cream). We will recruit 66 healthy male and female participants, aged 20 to 65 years, who have been diagnosed with dry skin conditions. Participants will be randomly allocated to receive either the proposed herbal moisturising cream or a placebo cream for four weeks. Each participant will be examined for signs and symptoms before and after using the cream. Skin hydration, sebum (oily secretion) levels and transepidermal water loss (TEWL; constitutive loss of water from the skin surface) will be assessed. Participants will also be asked to fill out a health-related quality of life questionnaire. Safety will be assessed using blood tests, urine analysis, a pregnancy test, and the assessment of vital signs. Discussion This trial will utilise high-quality methodologies in accordance with both consolidated standards for reporting trials guidelines and the guidelines for clinical trials of cosmetics products that are aimed at expressions and advertisement approval in Korea. It will evaluate the clinical efficacy and safety of a proposed herbal moisturising cream containing Arctium lappa L. seed extract to treat dry skin conditions and provide itch relief. Moreover, we will also employ

  17. Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

    2017-01-01

    To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Askari, Neda; Moin, Mahdieh; Sanati, Mohammad; Tajdini, Masih; Hosseini, Seyed-Mohammad-Reza; Modabbernia, Amirhossein; Najand, Babak; Salimi, Samrand; Tabrizi, Mina; Ashrafi, Mandana; Hajiaghaee, Reza; Akhondzadeh, Shahin

    2012-10-01

    Several small studies have shown beneficial effects of ondansetron, a serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients with OCD is still unclear. Granisetron does not alter cytochrome P450 activity and might have a lower risk of drug interactions, a longer duration of action and a better tolerability profile than other 5-HT(3) receptor antagonists. The objective of this study was to assess the efficacy and tolerability of granisetron augmentation of fluvoxamine in patients with OCD. This was a two-centre, randomized, double-blind, placebo-controlled, parallel-group study conducted from November 2011 to March 2012. The study setting was outpatient clinics of two large referral centres. Study participants were men and women, aged 18-60 years, who met the diagnostic criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21. Participants were randomly assigned to granisetron (Kytril(®); SmithKline Beecham, Philadelphia, PA, USA) 1 mg every 12 hours or placebo every 12 hours in addition to fluvoxamine for 8 weeks. Patients were assessed using the Y-BOCS at baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was the difference in the score change of Y-BOCS total score from baseline to week 8 between the two groups. We also compared changes in the obsession and compulsion subscales of the Y-BOCS, and frequencies of partial response (≥25% reduction in Y-BOCS score), complete response (≥35% reduction in Y-BOCS score) and remission (Y-BOCS score ≤16) between the two groups. Of the 42 included patients, 39 (20 in the placebo group, 19 in the granisetron group) completed the study. Significant time X treatment interaction was observed for total Y-BOCS (F [2.097, 79.678] = 4.941, p = 0.009), obsession (F [2.337, 88.799] = 4.938, p = 0.006) and compulsion (F [2.050, 77

  19. 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.

  20. Safety of Russian-backbone seasonal trivalent, live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh.

    Science.gov (United States)

    Ortiz, Justin R; Goswami, Doli; Lewis, Kristen D C; Sharmeen, Amina Tahia; Ahmed, Moshtaq; Rahman, Mustafizur; Rahman, Mohammed Z; Feser, Jodi; Neuzil, Kathleen M; Brooks, W Abdullah

    2015-06-26

    Live-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings. We conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations. Three hundred children were randomized and administered LAIV (n=150) or placebo (n=150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n=13 vs. n=16, p=0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p=0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events. In this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian

  1. Long-Term Pain Treatment Did Not Improve Sleep in Nursing Home Patients with Comorbid Dementia and Depression: A 13-Week Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Kjersti M. Blytt

    2018-02-01

    Full Text Available Objective: Previous research indicates that pain treatment may improve sleep among nursing home patients. We aimed to investigate the long-term effect of pain treatment on 24-h sleep patterns in patients with comorbid depression and dementia.Design: A 13-week, multicenter, parallel-group, double-blind, placebo-controlled randomized clinical trial conducted between August 2014 and September 2016.Setting: Long-term patients from 47 nursing homes in Norway.Participants: We included 106 patients with comorbid dementia and depression according to the Mini Mental Status Examination (MMSE and the Cornell Scale for Depression in Dementia (CSDD.Intervention: Patients who were not using analgesics were randomized to receive either paracetamol (3 g/day or placebo tablets. Those who already received pain treatment were randomized to buprenorphine transdermal system (maximum 10 μg/h/7 days or placebo transdermal patches.Measurements: Sleep was assessed continuously for 7 days by actigraphy, at baseline and in week 13. Total sleep time (TST, sleep efficiency (SE, sleep onset latency (SOL, wake after sleep onset (WASO, early morning awakening (EMA, and number of wake bouts (NoW were evaluated. In addition, daytime total sleep time (DTS was estimated. Pain was assessed with Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2.Results: The linear mixed model analyses for TST, SE, SOL, WASO, EMA, NoW and DTS showed no statistically significant differences between patients who received active pain treatment and those who received placebo. Post hoc subgroup analyses showed that there were no statistically significant differences between active treatment and placebo from baseline to week 13 in patients who were in pain (MOBID-2 ≥ 3 at baseline, or in patients who had poor sleep (defined as SE < 85% at baseline. Patients who received active buprenorphine showed an increase in TST and SE compared to those who received active paracetamol

  2. Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction-A prospective, randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Kamenov, Zdravko; Fileva, Svetlana; Kalinov, Krassimir; Jannini, Emmanuele A

    2017-05-01

    The primary objectives were to compare the efficacy of extracts of the plant Tribulus terrestris (TT; marketed as Tribestan), in comparison with placebo, for the treatment of men with erectile dysfunction (ED) and with or without hypoactive sexual desire disorder (HSDD), as well as to monitor the safety profile of the drug. The secondary objective was to evaluate the level of lipids in blood during treatment. Phase IV, prospective, randomized, double-blind, placebo-controlled clinical trial in parallel groups. This study included 180 males aged between 18 and 65 years with mild or moderate ED and with or without HSDD: 90 were randomized to TT and 90 to placebo. Patients with ED and hypertension, diabetes mellitus, and metabolic syndrome were included in the study. In the trial, an herbal medicine intervention of Bulgarian origin was used (Tribestan ® , Sopharma AD). Each Tribestan film-coated tablet contains the active substance Tribulus terrestris, herba extractum siccum (35-45:1) 250mg which is standardized to furostanol saponins (not less than 112.5mg). Each patient received orally 3×2 film-coated tablets daily after meals, during the 12-week treatment period. At the end of each month, participants' sexual function, including ED, was assessed by International Index of Erectile Function (IIEF) Questionnaire and Global Efficacy Question (GEQ). Several biochemical parameters were also determined. The primary outcome measure was the change in IIEF score after 12 weeks of treatment. Complete randomization (random sorting using maximum allowable% deviation) with an equal number of patients in each sequence was used. This randomization algorithm has the restriction that unequal treatment allocation is not allowed; that is, all groups must have the same target sample size. Patients, investigational staff, and data collectors were blinded to treatment. All outcome assessors were also blinded to group allocation. 86 patients in each group completed the study. The IIEF

  3. Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

    Directory of Open Access Journals (Sweden)

    Marshall J Glesby

    Full Text Available Recombinant human growth hormone (rhGH reduces visceral adipose tissue (VAT volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI and subcutaneous adipose tissue (SAT volume.Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI and dual Xray absorptiometry (DEXA. Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02; by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03 differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004, increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH but not in the rosiglitazone alone (-2.5% or control arms (-1.9%. SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter.The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT.Clinicaltrials.gov NCT00130286.

  4. Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

    Science.gov (United States)

    Glesby, Marshall J; Albu, Jeanine; Chiu, Ya-Lin; Ham, Kirsis; Engelson, Ellen; He, Qing; Muthukrishnan, Varalakshmi; Ginsberg, Henry N; Donovan, Daniel; Ernst, Jerry; Lesser, Martin; Kotler, Donald P

    2013-01-01

    Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. Clinicaltrials.gov NCT00130286.

  5. Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study.

    Science.gov (United States)

    Roth, Thomas; Krystal, Andrew; Steinberg, Frank J; Singh, Nikhilesh N; Moline, Margaret

    2013-02-01

    To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the-night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings. Multicenter randomized, double-blind, placebo-controlled, parallel-group. Outpatient. There were 295 adults (median age 43 y; 68.1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTN awakenings/wk during screening). After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures. ZST significantly (P Zolpidem Tartrate Tablet in Adult Patients with Insomnia" http://www.clinicaltrials.gov/ct2/show/NCT00466193?spons=%22Transcept+Pharmaceuticals%22&spons_ex=Y&rank=2

  6. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

    Science.gov (United States)

    Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

    2017-06-01

    Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Udani, Jay K; George, Annie A; Musthapa, Mufiza; Pakdaman, Michael N; Abas, Azreena

    2014-01-01

    Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40-65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.

  8. Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Jay K. Udani

    2014-01-01

    Full Text Available Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali, which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40–65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P<0.05 for all. Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.

  9. Efficacy of Wobe-Mugos registered E for reduction of oral mucositis after radiotherapy. Results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study

    International Nuclear Information System (INIS)

    Doerr, W.; Herrmann, T.

    2007-01-01

    Purpose: To investigate the efficacy and safety of Wobe-Mugos registered E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis. Patients and Methods: The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos registered E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. Results: Wobe-Mugos registered E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos registered E group. Conclusion: The present study failed to demonstrate any effect of treatment with Wobe-Mugos registered E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis. (orig.)

  10. 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...

  11. 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...

  12. 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...

  13. 5-HT3 antagonist for cognition improvement in schizophrenia: a double blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Neyousha Mohammadi

    2010-01-01

    Full Text Available   Abstract   Introduction: Patients with schizophrenia characteristically exhibit cognitive deficits. The level of cognitive impairment is found to predict the functional outcome of the illness more strongly than the severity of positive or negative symptoms. The purpose of this study was to assess the efficacy of ondansetron, a 5-HT3 receptor antagonist as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments.   Methods: This investigation was a 12-week, double blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments. All participants met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive ondansetron (8 mg/day or the placebo in addition to risperidone. Cognition was measured by a cognitive battery. Patients were assessed at baseline and after 8, and 12 weeks after the medication started.   Results: Administration of ondansetron significantly improved visual memory based on improvement on visual reproduction, visual paired associate and figural memory sub tests of Wechsler Memory Scale Revised.  Discussion: The present study indicates ondansetron as potential adjunctive treatment strategy for chronic schizophrenia particularly for cognitive impairments.

  14. Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Pase, Matthew P; Scholey, Andrew B; Pipingas, Andrew; Kras, Marni; Nolidin, Karen; Gibbs, Amy; Wesnes, Keith; Stough, Con

    2013-05-01

    This study aimed to examine the acute and sub-chronic effects of cocoa polyphenols on cognition and mood. In a randomized, double-blind study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg or 0 mg of polyphenols (placebo) in a parallel-groups design. Participants consumed their assigned treatment once daily for 30 days. Cognition was measured with the Cognitive Drug Research system and self-rated mood with the Bond-Lader Visual Analogue Scale. Participants were tested at baseline, at 1, 2.5 and 4 h after a single acute dose and again after receiving 30 days of treatment. In total, 72 participants completed the trial. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to placebo. Mood was unchanged by treatment acutely while cognition was unaffected by treatment at all time points. This randomized controlled trial is perhaps the first to demonstrate the positive effects of cocoa polyphenols on mood in healthy participants. This provides a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.

  15. Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    McGraw T

    2016-07-01

    Full Text Available Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC of polyethylene glycol (PEG 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g ASC or placebo solution for 14 days. The study comprised a screening period (visit 1, endoscopy procedure (visits 2 and 3, and follow-up telephone calls 30 days post-treatment. Safety end points included adverse events (AEs, clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions.Results: A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment or visit 3 (after treatment. Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo – nonsignificant difference of -7.5% (95% CI: -21.3, 6.3 between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because

  16. 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.

  17. Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Gagliardi, Lucia; Nenke, Marni A; Thynne, Tilenka R J; von der Borch, Jenny; Rankin, Wayne A; Henley, David E; Sorbello, Jane; Inder, Warrick J; Torpy, David J

    2014-11-01

    Patients with Addison's disease (AD) report impaired subjective health status (SHS). Since cortisol exhibits a robust circadian cycle that entrains other biological clocks, impaired SHS may be due to the noncircadian cortisol profile achieved with conventional glucocorticoid replacement. Continuous subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol profile, but its effects on SHS have not been objectively evaluated. The aim of this study was to determine the effect of CSHI on SHS in AD. This was a multicentre, double-blind, placebo-controlled trial of CSHI vs oral glucocorticoid therapy. Participants received in random order 4 weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a 2-week washout period. SHS was assessed using the Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS), Gastrointestinal Symptom Rating Scale (GSRS); and Addison's Quality of Life Questionnaire (AddiQoL). Participants were asked their (blinded) treatment preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary cortisol collections compared cortisol exposure during each treatment. Ten participants completed the study. Baseline SHS scores (mean ± SE) were consistent with mild impairment: SF-36 physical component summary 48.4 (± 2.4), mental component summary 53.3 (± 3.0); GHQ-28 18.1 (± 3.3); GSRS 3.7 (± 1.6), and AddiQoL 94.7 (± 3.7). FS was similar to other AD cohorts 13.5 (± 1.0) (P = 0.82). UFC between treatments was not different (P = 0.87). The salivary cortisol at 0800 h was higher during CSHI (P = 0.03), but not at any other time points measured. There was no difference between the treatments in the SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and one was uncertain. Biochemical measurements indicate similar cortisol exposure during each treatment period, although a more circadian pattern was evident during CSHI. CSHI does not

  18. Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Smith, Stephen R; Murray, David; Pockney, Peter G; Bendinelli, Cino; Draganic, Brian D; Carroll, Rosemary

    2018-01-01

    Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking. The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage. This was a prospective, double-blind, placebo-controlled, randomized clinical trial. The study was conducted at a tertiary referral university hospital in Australia. Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265). A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo. The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates. There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use. A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes. Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

  19. Green tea polyphenols and Tai Chi for bone health: Designing a placebo-controlled randomized trial

    Directory of Open Access Journals (Sweden)

    Chyu Ming-Chien

    2009-09-01

    model of repeated measurements with random effect error terms was applied. Traditional procedures such as ANCOVA, chi-squared analysis, and regression were used for comparisons. Discussion We present the rationale, design, and methodology of a placebo-controlled randomized trial to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in osteopenic postmenopausal women. Trial registration ClinicalTrials.gov identifier: NCT00625391

  20. 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.

  1. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial.

    Science.gov (United States)

    Chollet, François; Tardy, Jean; Albucher, Jean-François; Thalamas, Claire; Berard, Emilie; Lamy, Catherine; Bejot, Yannick; Deltour, Sandrine; Jaillard, Assia; Niclot, Philippe; Guillon, Benoit; Moulin, Thierry; Marque, Philippe; Pariente, Jérémie; Arnaud, Catherine; Loubinoux, Isabelle

    2011-02-01

    Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial

  2. 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

  3. 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.

  4. Electroacupuncture Versus Gabapentin for Hot Flashes Among Breast Cancer Survivors: A Randomized Placebo-Controlled Trial

    Science.gov (United States)

    Mao, Jun J.; Bowman, Marjorie A.; Xie, Sharon X.; Bruner, Deborah; DeMichele, Angela; Farrar, John T.

    2015-01-01

    Purpose Hot flashes are a common and debilitating symptom among survivors of breast cancer. This study aimed at evaluating the effects of electroacupuncture (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer, with a specific focus on the placebo and nocebo effects. Patients and Methods We conducted a randomized controlled trial involving 120 survivors of breast cancer experiencing bothersome hot flashes twice per day or greater. Participants were randomly assigned to receive 8 weeks of EA or GP once per day with validated placebo controls (sham acupuncture [SA] or placebo pills [PPs]). The primary end point was change in the hot flash composite score (HFCS) between SA and PP at week 8, with secondary end points including group comparisons and additional evaluation at week 24 for durability of treatment effects. Results By week 8, SA produced significantly greater reduction in HFCS than did PP (−2.39; 95% CI, −4.60 to −0.17). Among all treatment groups, the mean reduction in HFCS was greatest in the EA group, followed by SA, GP, and PP (−7.4 v −5.9 v −5.2 v −3.4; P = < .001). The pill groups had more treatment-related adverse events than did the acupuncture groups: GP (39.3%), PP (20.0%), EA (16.7%), and SA (3.1%), with P = .005. By week 24, HFCS reduction was greatest in the EA group, followed by SA, PP, and GP (−8.5 v −6.1 v −4.6 v −2.8; P = .002). Conclusion Acupuncture produced larger placebo and smaller nocebo effects than did pills for the treatment of hot flashes. EA may be more effective than GP, with fewer adverse effects for managing hot flashes among breast cancer survivors; however, these preliminary findings need to be confirmed in larger randomized controlled trials with long-term follow-up. PMID:26304905

  5. Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Park, Susanna B; Vucic, Steve; Cheah, Benjamin C; Lin, Cindy S-Y; Kirby, Adrienne; Mann, Kristy P; Zoing, Margie C; Winhammar, Jennica; Kiernan, Matthew C

    2015-12-01

    Abnormalities in membrane excitability and Na(+) channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na(+) channel blocker and membrane stabiliser flecainide in ALS. A double-blind, placebo-controlled, randomised clinical trial of flecainide (200 mg/day) for 32-weeks with a 12-week lead-in phase was conducted in participants with probable or definite ALS recruited from multiple Australian centres (ANZCT Registry number ACTRN12608000338369). Patients were reviewed by a cardiologist to rule out cardiac contraindications. Participants were randomly assigned (1:1) to flecainide or placebo using stratified permuted blocks by a central pharmacy. The primary outcome measure was the slope of decline of the ALS Functional Rating Scale-revised (ALS FRS-r) during the treatment period. Between March 11, 2008 and July 1, 2010, 67 patients were screened, 54 of whom were randomly assigned to receive flecainide (26 patients) or placebo (28 patients). Four patients in the flecainide group and three patients in the placebo group withdrew from the study. One patient in the flecainide group died during the study, attributed to disease progression. Flecainide was generally well tolerated, with no serious adverse events reported in either group. There was no significant difference in the rate of decline in the primary outcome measure ALS-FRS-r between placebo and flecainide treated patients (Flecainide 0.65 [95% CI 0.49 to 0.98]; Placebo 0.81 [0.49 to 2.12] P = 0.50). However, the rate of decline of the neurophysiological index was significantly reduced in the flecainide group (Flecainide 0.06 [0.01 to 0.11]; Placebo 0.14 [0.09 to 0.19], P = 0.02). Placebo-treated patients demonstrated greater CMAP amplitude reduction during the course of the study in the subset of patients with a reduced baseline CMAP amplitude (Flecainide: - 15 ± 12%; Placebo - 59 ± 12%; P = 0.03). Flecainide

  6. 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).

  7. Neck collar, "act-as-usual" or active mobilization for whiplash injury? A randomized parallel-group trial

    DEFF Research Database (Denmark)

    Kongsted, Alice; Montvilas, Erisela Qerama; Kasch, Helge

    2007-01-01

    practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to "act-as-usual," or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12......-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only. Methods. Participants were recruited from emergency units and general......Study Design. Randomized, parallel-group trial. Objective. To compare the effect of 3 early intervention strategies following whiplash injury. Summary of Background Data. Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion...

  8. Neck collar, "act-as-usual" or active mobilization for whiplash injury? A randomized parallel-group trial

    DEFF Research Database (Denmark)

    Kongsted, Alice; Montvilas, Erisela Qerama; Kasch, Helge

    2007-01-01

    Study Design. Randomized, parallel-group trial. Objective. To compare the effect of 3 early intervention strategies following whiplash injury. Summary of Background Data. Long-lasting pain and disability, known as chronic whiplash-associated disorder (WAD), may develop after a forced flexion......-extension trauma to the cervical spine. It is unclear whether this, in some cases disabling, condition can be prevented by early intervention. Active interventions have been recommended but have not been compared with information only. Methods. Participants were recruited from emergency units and general...... practitioners within 10 days after a whiplash injury and randomized to: 1) immobilization of the cervical spine in a rigid collar followed by active mobilization, 2) advice to "act-as-usual," or 3) an active mobilization program (Mechanical Diagnosis and Therapy). Follow-up was carried out after 3, 6, and 12...

  9. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes

    NARCIS (Netherlands)

    Kerkhoffs, G. M. M. J.; Struijs, P. A. A.; de Wit, C.; Rahlfs, V. W.; Zwipp, H.; van Dijk, C. N.

    2004-01-01

    Objective: To compare the effectiveness and safety of the triple combination Phlogenzym ( rutoside, bromelain, and trypsin) with double combinations, the single substances, and placebo. Design: Multinational, multicentre, double blind, randomised, parallel group design with eight groups structured

  10. 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.

  11. Renal effects of dexmedetomidine during coronary artery bypass surgery: a randomized placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Scheinin Harry

    2011-05-01

    Full Text Available Abstract Background Dexmedetomidine, an alpha2-adrenoceptor agonist, has been evaluated as an adjunct to anesthesia and for the delivery of sedation and perioperative hemodynamic stability. It provokes dose-dependent and centrally-mediated sympatholysis. Coronary artery bypass grafting (CABG with extracorporeal circulation is a stressful procedure increasing sympathetic nervous system activity which could attenuate renal function due the interrelation of sympathetic nervous system, hemodynamics and renal function. We tested the hypothesis that dexmetomidine would improve kidney function in patients undergoing elective CABG during the first two postoperative days. Methods This was a double-blind, randomized, parallel-group study. Patients with normal renal function and scheduled for elective CABG were randomized to placebo or to infusion of dexmedetomidine to achieve a pseudo steady-state plasma concentration of 0.60 ng/ml. The infusion was started after anesthesia induction and continued until 4 h after surgery. The primary endpoint was creatinine clearance. Other variables included urinary creatinine and output, fractional sodium and potassium excretion, urinary potassium, sodium and glucose, serum and urinary osmolality and plasma catecholamine concentrations. The data were analyzed with repeated-measures ANOVA or Cochran-Mantel-Haenszel test. Results Sixty-six of 87 randomized patients were evaluable for analysis. No significant between-group differences were recorded for any indices of renal function except for a mean 74% increase in urinary output with dexmedetomidine in the first 4 h after insertion of a urinary catheter (p Conclusions Use of intravenous dexmedetomidine did not alter renal function in this cohort of relatively low-risk elective CABG patients but was associated with an increase in urinary output. This study was carried out in 1994-1997 and was thus not registered.

  12. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vranken, J. H.; Hollmann, M. W.; van der Vegt, M. H.; Kruis, M. R.; Heesen, M.; Vos, K.; Pijl, A. J.; Dijkgraaf, M. G. W.

    2011-01-01

    The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief

  13. Pregabalin in patients with central neuropathic pain: a randomized, double-blind, placebo-controlled trial of a flexible-dose regimen

    NARCIS (Netherlands)

    Vranken, J. H.; Dijkgraaf, M. G. W.; Kruis, M. R.; van der Vegt, M. H.; Hollmann, M. W.; Heesen, M.

    2008-01-01

    The effective treatment of patients suffering from central neuropathic pain remains a clinical challenge, despite a standard pharmacological approach in combination with anticonvulsants and antidepressants. A randomized, double-blinded, placebo-controlled trial evaluated the effects of pregabalin on

  14. NMDA receptor antagonists interventions in schizophrenia: Meta-analysis of randomized, placebo-controlled trials.

    Science.gov (United States)

    Kishi, Taro; Iwata, Nakao

    2013-09-01

    We examined whether N-methyl d-aspartate (NMDA) receptor antagonists as adjunctive therapy have therapeutic potential for schizophrenia treatment. Systematic review of PubMed, Cochrane Library, PsycINFO and Google Scholar up until October 2012 and meta-analysis of randomized placebo-controlled trials were performed. Risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and standardized mean difference (SMD) were calculated. Results were across 8 studies and 406 patients (85.5% schizophrenia related disorder and 14.5% bipolar disorder) were included (amantadine: 5 trials and 220 patients, memantine: 3 trials and 186 patients). NMDA receptor antagonists (NMDAR-ANTs) as adjunctive therapy were not superior to placebo in overall (SMD = -0.25, CI = -0.72, 0.23, p = 0.31, N = 6, n = 347), positive symptoms (SMD = -0.20, CI = -0.70, 0.31, p = 0.44, N = 4, n = 205), and negative symptoms (SMD = -0.69, CI = -1.65, 0.27, p = 0.16, N = 4, n = 205), and Clinical Global Impression Severity scale (SMD = -0.27, CI = -1.20, 0.65, p = 0.56, N = 3, n = 177). There was also no significant difference in discontinuation rate between NMDAR-ANTs and placebo treatments (all cause: RR = 1.23, CI = 0.89-1.70, p = 0.20, N = 8, n = 396, side effects: RR = 1.86, CI = 0.84-4.13, p = 0.13, N = 6, n = 359, inefficacy/worsening psychosis: RR = 0.70, CI = 0.20-2.38, p = 0.56, N = 7, n = 380). However, memantine was favorable compared with placebo in Mini-Mental State Examination in schizophrenia (SMD = -0.77, CI = -1.27, -0.28, p = 0.002, N = 3, n = 71). While NMDAR-ANTs caused weight loss compared with placebo (SMD = -0.42, CI = -0.73, -0.11, p = 0.008, N = 3, n = 165), amantadine caused more frequent insomnia than placebo (RR = 3.83, CI = 1.41-10.38, p = 0.008, NNH = 9, p = 0.002, N = 2, n = 147). Our results indicate that NMDAR-ANTs as adjunctive therapy may improve

  15. Liposomal bupivacaine decreases pain following retropubic sling placement: a randomized placebo-controlled trial.

    Science.gov (United States)

    Mazloomdoost, Donna; Pauls, Rachel N; Hennen, Erin N; Yeung, Jennifer Y; Smith, Benjamin C; Kleeman, Steven D; Crisp, Catrina C

    2017-11-01

    Midurethral slings are commonly used to treat stress urinary incontinence. Pain control, however, may be a concern. Liposomal bupivacaine is a local anesthetic with slow release over 72 hours, demonstrated to lower pain scores and decrease narcotic use postoperatively. The purpose of this study was to examine the impact of liposomal bupivacaine on pain scores and narcotic consumption following retropubic midurethral sling placement. This randomized, placebo-controlled trial enrolled women undergoing retropubic midurethral sling procedures with or without concomitant anterior or urethrocele repair. Subjects were allocated to receive liposomal bupivacaine (intervention) or normal saline placebo injected into the trocar paths and vaginal incision at the conclusion of the procedure. At the time of drug administration, surgeons became unblinded, but did not collect outcome data. Participants remained blinded to treatment. Surgical procedures and perioperative care were standardized. The primary outcome was the visual analog scale pain score 4 hours after discharge home. Secondary outcomes included narcotic consumption, time to first bowel movement, and pain scores collected in the mornings and evenings until postoperative day 6. The morning pain item assessed "current level of pain"; the evening items queried "current level of pain," "most intense pain today," "average pain today with activity," and "average pain today with rest." Likert scales were used to measure satisfaction with pain control at 1- and 2-week postoperative intervals. Sample size calculation deemed 52 subjects per arm necessary to detect a mean difference of 10 mm on a 100-mm visual analog scale. To account for 10% drop out, 114 participants were needed. One hundred fourteen women were enrolled. After 5 exclusions, 109 cases were analyzed: 54 women received intervention, and 55 women received placebo. Mean participant age was 52 years, and mean body mass index was 30.4 kg/m 2 . Surgical and

  16. Probiotic Supplementation in Chronic Kidney Disease: A Double-blind, Randomized, Placebo-controlled Trial.

    Science.gov (United States)

    Borges, Natália A; Carmo, Flávia L; Stockler-Pinto, Milena B; de Brito, Jessyca S; Dolenga, Carla J; Ferreira, Dennis C; Nakao, Lia S; Rosado, Alexandre; Fouque, Denis; Mafra, Denise

    2018-01-01

    The objective of the study was to evaluate the effects of probiotic supplementation on the gut microbiota profile and inflammatory markers in chronic kidney disease patients undergoing maintenance hemodialysis (HD). This was a randomized, double-blind, placebo-controlled study. Forty-six HD patients were assigned to receive 1 of 2 treatments: probiotic (n = 23; Streptococcus thermophilus, Lactobacillus acidophilus e Bifidobacterialongum, 90 billion colony-forming units per day) or placebo (n = 23) daily for 3 months. Blood and feces were collected at baseline and after intervention. The inflammatory markers (C-reactive protein and interleukin-6) were analyzed by immunoenzymatic assay (enzyme-linked immunosorbent assay). Uremic toxins plasma levels (indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid) were obtained by Reversed-Phase High-Performance Liquid Chromatography. Routine laboratory parameters were measured by standard techniques. Fecal pH was measured by the colorimetric method, and the gut microbiota profile was assessed by Denaturing Gradient Gel Electrophoresis analysis. Sixteen patients remained in the probiotic group (11 men, 53.6 ± 11.0 year old, 25.3 ± 4.6 kg/m 2 ) and 17 in the placebo group (10 men, 50.3 ± 8.5 year old, 25.2 ± 5.7 kg/m 2 ). After probiotic supplementation there was a significant increase in serum urea (from 149.6 ± 34.2 mg/dL to 172.6 ± 45.0 mg/dL, P = .02), potassium (from 4.4 ± 0.4 mmol/L to 4.8 ± 0.4 mmol/L, P = .02), and indoxyl sulfate (from 31.2 ± 15.9 to 36.5 ± 15.0 mg/dL, P = .02). The fecal pH was reduced from 7.2 ± 0.8 to 6.5 ± 0.5 (P = .01). These parameters did not change significantly in placebo group. Changes in the percentage delta (Δ) between groups were exhibited with no statistical differences observed. The inflammatory markers and gut profile were not altered by supplementation. Aprobiotic supplementation failed to reduce uremic toxins and

  17. 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...

  18. Threshold electrical stimulation (TES) in ambulant children with CP: a randomized double-blind placebo-controlled clinical trial

    DEFF Research Database (Denmark)

    Dali, Christine í; Hansen, Flemming Juul; Pedersen, Søren Anker

    2002-01-01

    A randomized double-blind placebo-controlled clinical trial was carried out to determine whether a group of stable children with cerebral palsy (36 males, 21 females; mean age 10 years 11 months, range 5 to 18 years) would improve their motor skills after 12 months of threshold electrical...... stimulation (TES). Two thirds received active and one third received inactive stimulators. For the primary outcome we constructed a set of plausible motor function tests and studied the change in summary indices of the performance measurements. Tests were videotaped and assessed blindly to record qualitative...

  19. 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

  20. Reduction of body fat and improved lipid profile associated with daily consumption of a Puer tea extract in a hyperlipidemic population: a randomized placebo-controlled trial.

    Science.gov (United States)

    Jensen, Gitte S; Beaman, Joni L; He, Yi; Guo, Zhixin; Sun, Henry

    2016-01-01

    The goal for this study was to evaluate the effects of daily consumption of Puer tea extract (PTE) on body weight, body-fat composition, and lipid profile in a non-Asian population in the absence of dietary restrictions. A randomized, double-blind, placebo-controlled study design was used. A total of 59 overweight or mildly obese subjects were enrolled upon screening to confirm fasting cholesterol level at or above 220 mg/dL (5.7 mmol/dL). After giving informed consent, subjects were randomized to consume PTE (3 g/day) or placebo for 20 weeks. At baseline and at 4-week intervals, blood lipids, C-reactive protein, and fasting blood glucose were evaluated. A dual-energy X-ray absorptiometry scan was performed at baseline and at study exit to evaluate changes to body composition. Appetite and physical and mental energy were scored at each visit using visual analog scales (0-100). Consumption of PTE was associated with statistically significant weight loss when compared to placebo (PConsumption of PTE was associated with improvements to lipid profile, including a mild reduction in cholesterol and the cholesterol:high-density lipoprotein ratio after only 4 weeks, as well as a reduction in triglycerides and very small-density lipoproteins, where average blood levels reached normal range at 8 weeks and remained within normal range for the duration of the study (Pconsumption of PTE was associated with significant weight loss, reduced body mass index, and an improved lipid profile.

  1. Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

    Science.gov (United States)

    Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

    2014-03-01

    Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy

  2. Effectiveness of a mobile cooperation intervention during the clinical practicum of nursing students: a parallel group randomized controlled trial protocol.

    Science.gov (United States)

    Strandell-Laine, Camilla; Saarikoski, Mikko; Löyttyniemi, Eliisa; Salminen, Leena; Suomi, Reima; Leino-Kilpi, Helena

    2017-06-01

    The aim of this study was to describe a study protocol for a study evaluating the effectiveness of a mobile cooperation intervention to improve students' competence level, self-efficacy in clinical performance and satisfaction with the clinical learning environment. Nursing student-nurse teacher cooperation during the clinical practicum has a vital role in promoting the learning of students. Despite an increasing interest in using mobile technologies to improve the clinical practicum of students, there is limited robust evidence regarding their effectiveness. A multicentre, parallel group, randomized, controlled, pragmatic, superiority trial. Second-year pre-registration nursing students who are beginning a clinical practicum will be recruited from one university of applied sciences. Eligible students will be randomly allocated to either a control group (engaging in standard cooperation) or an intervention group (engaging in mobile cooperation) for the 5-week the clinical practicum. The complex mobile cooperation intervention comprises of a mobile application-assisted, nursing student-nurse teacher cooperation and a training in the functions of the mobile application. The primary outcome is competence. The secondary outcomes include self-efficacy in clinical performance and satisfaction with the clinical learning environment. Moreover, a process evaluation will be undertaken. The ethical approval for this study was obtained in December 2014 and the study received funding in 2015. The results of this study will provide robust evidence on mobile cooperation during the clinical practicum, a research topic that has not been consistently studied to date. © 2016 John Wiley & Sons Ltd.

  3. Double-blind, parallel-group evaluation of etodolac and naproxen in patients with acute sports injuries.

    Science.gov (United States)

    D'Hooghe, M

    1992-01-01

    The efficacy and safety of etodolac and naproxen were compared in a double-blind, randomized, parallel-group outpatient study. Patients with acute sports injuries were assigned to receive either etodolac 300 mg TID (50 patients) or naproxen 500 mg BID (49 patients) for up to 7 days. Assessments were made at the pretreatment screening (baseline) and at days 2, 3, 4, and 7 of treatment. Assessments included patient and physician global evaluations, spontaneous and induced pain intensity, range of motion, tenderness, heat, degree of swelling, and degree of erythema. Safety assessments, including laboratory profiles, were made at pretreatment and at final evaluation; patients' complaints were elicited at all visits. Both treatment groups showed significant (P less than or equal to 0.05) improvement from baseline for all efficacy parameters by day 2 and thereafter at all time points. Improvement was similar for the two groups. No patients in either group withdrew from the study because of drug-related adverse reactions. The results of this study indicate that etodolac (900 mg/day) is effective and well tolerated as an analgesic and anti-inflammatory in acute sports injuries and is comparable to naproxen (1000 mg/day).

  4. Effect of Metformin on Plasma Fibrinogen Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

    Science.gov (United States)

    Simental-Mendia, Luis E; Pirro, Matteo; Atkin, Stephen L; Banach, Maciej; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

    2018-01-01

    Fibrinogen is a key mediator of thrombosis and it has been implicated in the pathogenesis of atherosclerosis. Because metformin has shown a potential protective effect on different atherothrombotic risk factors, we assessed in this meta-analysis its effect on plasma fibrinogen concentrations. A systematic review and meta-analysis was carried out to identify randomized placebo-controlled trials evaluating the effect of metformin administration on fibrinogen levels. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases (by June 2, 2017) and quality of studies was performed according to Cochrane criteria. Quantitative data synthesis was conducted using a random-effects model and sensitivity analysis by the leave-one-out method. Meta-regression analysis was performed to assess the modifiers of treatment response. Meta-analysis of data from 9 randomized placebo-controlled clinical trials with 2302 patients comprising 10 treatment arms did not suggest a significant change in plasma fibrinogen concentrations following metformin therapy (WMD: -0.25 g/L, 95% CI: -0.53, 0.04, p = 0.092). The effect size was robust in the leave-one-out sensitivity analysis and remained non-significant after omission of each single study from the meta-analysis. No significant effect of metformin on plasma fibrinogen concentrations was demonstrated in the current meta-analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa

    DEFF Research Database (Denmark)

    Miller, I; Lynggaard, C D; Lophaven, S

    2011-01-01

    BACKGROUND: Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. OBJECTIVES: To test the efficacy of adalimumab in HS. METHODS: This was a prospective, randomized, double-blinded, placebo-controlled,......BACKGROUND: Hidradenitis suppurativa (HS) has an impact on patients' quality of life. Treatment of HS is generally unsatisfactory, thus new treatments are needed. OBJECTIVES: To test the efficacy of adalimumab in HS. METHODS: This was a prospective, randomized, double-blinded, placebo......-controlled, two-centre clinical trial conducted in Denmark. Inclusion criteria were age above 18 years and a clinical diagnosis of moderate to severe HS defined as Hurley stage II or III for at least 6 months. The patients were randomized 1:2 (placebo/active). Actively treated patients received adalimumab 80 mg...... subcutaneously (s.c.) at baseline followed by 40 mg s.c. every other week for 12 weeks. Placebo-treated patients received identical-looking injections with no active ingredient. The medicine was dispensed in sequentially numbered computer-randomized containers. Participants, care givers and those assessing...

  6. Ankle manual therapy for individuals with post-acute ankle sprains: description of a randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Davenport, Todd E; Kulig, Kornelia; Fisher, Beth E

    2010-10-19

    Ankle sprains are common within the general population and can result in prolonged disablement. Limited talocrural dorsiflexion range of motion (DF ROM) is a common consequence of ankle sprain. Limited talocrural DF ROM may contribute to persistent symptoms, disability, and an elevated risk for re-injury. As a result, many health care practitioners use hands-on passive procedures with the intention of improving talocrural joint DF ROM in individuals following ankle sprains. Dosage of passive hands-on procedures involves a continuum of treatment speeds. Recent evidence suggests both slow- and fast-speed treatments may be effective to address disablement following ankle sprains. However, these interventions have yet to be longitudinally compared against a placebo study condition. We developed a randomized, placebo-controlled clinical trial designed to test the hypotheses that hands-on treatment procedures administered to individuals following ankle sprains during the post-acute injury period can improve short-, intermediate-, and long-term disablement, as well as reduce the risk for re-injury. This study is designed to measure the clinical effects of hands-on passive stretching treatment procedures directed to the talocrural joint that vary in treatment speed during the post-acute injury period, compared to hands-on placebo control intervention. http://www.clinicaltrials.gov identifier NCT00888498.

  7. Ankle manual therapy for individuals with post-acute ankle sprains: description of a randomized, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Fisher Beth E

    2010-10-01

    Full Text Available Abstract Background Ankle sprains are common within the general population and can result in prolonged disablement. Limited talocrural dorsiflexion range of motion (DF ROM is a common consequence of ankle sprain. Limited talocrural DF ROM may contribute to persistent symptoms, disability, and an elevated risk for re-injury. As a result, many health care practitioners use hands-on passive procedures with the intention of improving talocrural joint DF ROM in individuals following ankle sprains. Dosage of passive hands-on procedures involves a continuum of treatment speeds. Recent evidence suggests both slow- and fast-speed treatments may be effective to address disablement following ankle sprains. However, these interventions have yet to be longitudinally compared against a placebo study condition. Methods/Design We developed a randomized, placebo-controlled clinical trial designed to test the hypotheses that hands-on treatment procedures administered to individuals following ankle sprains during the post-acute injury period can improve short-, intermediate-, and long-term disablement, as well as reduce the risk for re-injury. Discussion This study is designed to measure the clinical effects of hands-on passive stretching treatment procedures directed to the talocrural joint that vary in treatment speed during the post-acute injury period, compared to hands-on placebo control intervention. Trial Registration http://www.clinicaltrials.gov identifier NCT00888498.

  8. A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults

    Directory of Open Access Journals (Sweden)

    Ha Ki-Chan

    2012-02-01

    Full Text Available Abstracts Background Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. Methods/Design We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. Discussion This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. Trial Registration NCT01478009.

  9. [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.

  10. 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.

  11. [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.

  12. Results of a non-specific immunomodulation therapy on chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial

    DEFF Research Database (Denmark)

    Torre-Amione, G.; Anker, S.D.; Bourge, R.C.

    2008-01-01

    Background Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. Methods We did a double-blind, placebo-controlled s......Background Evidence suggests that inflammatory mediators contribute to development and progression of chronic heart failure. We therefore tested the hypothesis that immunomodulation might counteract this pathophysiological mechanism in patients. Methods We did a double-blind, placebo......-controlled study of a device-based non-specific immunomodulation therapy (IMT) in patients with New York Heart Association (NYHA) functional class II-IV chronic heart failure, left ventricular (LV) systolic dysfunction, and hospitalisation for heart failure or intravenous drug therapy in an outpatient setting......-0 . 95; p=0.02) and a 39% (0.61; 95% CI 0 . 46-0.80; p=0 . 0003) reduction in the risk of primary endpoint events, respectively. Interpretation Non-specific immunomodulation may have a role as a potential treatment for a large segment of the heart failure population, which includes patients without...

  13. Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study.

    Science.gov (United States)

    Kobalava, Zhanna; Villevalde, Svetlana; Kotovskaya, Yulia; Hinrichsen, Holger; Petersen-Sylla, Marc; Zaehringer, Andreas; Pang, Yinuo; Rajman, Iris; Canadi, Jasna; Dahlke, Marion; Lloyd, Peter; Halabi, Atef

    2015-06-01

    Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin. This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg(-1)  day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls. A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study. The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment. © 2014 The British Pharmacological Society.

  14. Beyond Silence: A Randomized, Parallel-Group Trial Exploring the Impact of Workplace Mental Health Literacy Training with Healthcare Employees.

    Science.gov (United States)

    Moll, Sandra E; Patten, Scott; Stuart, Heather; MacDermid, Joy C; Kirsh, Bonnie

    2018-01-01

    This study sought to evaluate whether a contact-based workplace education program was more effective than standard mental health literacy training in promoting early intervention and support for healthcare employees with mental health issues. A parallel-group, randomised trial was conducted with employees in 2 multi-site Ontario hospitals with the evaluators blinded to the groups. Participants were randomly assigned to 1 of 2 group-based education programs: Beyond Silence (comprising 6 in-person, 2-h sessions plus 5 online sessions co-led by employees who personally experienced mental health issues) or Mental Health First Aid (a standardised 2-day training program led by a trained facilitator). Participants completed baseline, post-group, and 3-mo follow-up surveys to explore perceived changes in mental health knowledge, stigmatized beliefs, and help-seeking/help-outreach behaviours. An intent-to-treat analysis was completed with 192 participants. Differences were assessed using multi-level mixed models accounting for site, group, and repeated measurement. Neither program led to significant increases in help-seeking or help-outreach behaviours. Both programs increased mental health literacy, improved attitudes towards seeking treatment, and decreased stigmatized beliefs, with sustained changes in stigmatized beliefs more prominent in the Beyond Silence group. Beyond Silence, a new contact-based education program customised for healthcare workers was not superior to standard mental health literacy training in improving mental health help-seeking or help-outreach behaviours in the workplace. The only difference was a reduction in stigmatized beliefs over time. Additional research is needed to explore the factors that lead to behaviour change.

  15. Efficacy and tolerability of topical sertaconazole versus topical terbinafine in localized dermatophytosis: A randomized, observer-blind, parallel group study.

    Science.gov (United States)

    Chatterjee, Dattatreyo; Ghosh, Sudip Kumar; Sen, Sukanta; Sarkar, Saswati; Hazra, Avijit; De, Radharaman

    2016-01-01

    Epidermal dermatophyte infections most commonly manifest as tinea corporis or tinea cruris. Topical azole antifungals are commonly used in their treatment but literature suggests that most require twice-daily application and provide lower cure rates than the allylamine antifungal terbinafine. We conducted a head-to-head comparison of the effectiveness of the once-daily topical azole, sertaconazole, with terbinafine in these infections. We conducted a randomized, observer-blind, parallel group study (Clinical Trial Registry India [CTRI]/2014/09/005029) with adult patients of either sex presenting with localized lesions. The clinical diagnosis was confirmed by potassium hydroxide smear microscopy of skin scrapings. After baseline assessment of erythema, scaling, and pruritus, patients applied either of the two study drugs once daily for 2 weeks. If clinical cure was not seen at 2 weeks, but improvement was noted, application was continued for further 2 weeks. Patients deemed to be clinical failure at 2 weeks were switched to oral antifungals. Overall 88 patients on sertaconazole and 91 on terbinafine were analyzed. At 2 weeks, the clinical cure rates were comparable at 77.27% (95% confidence interval [CI]: 68.52%-86.03%) for sertaconazole and 73.63% (95% CI 64.57%-82.68%) for terbinafine ( P = 0.606). Fourteen patients in either group improved and on further treatment showed complete healing by another 2 weeks. The final cure rate at 4 weeks was also comparable at 93.18% (95% CI 88.75%-97.62%) and 89.01% (95% CI 82.59%-95.44%), respectively ( P = 0.914). At 2 weeks, 6 (6.82%) sertaconazole and 10 (10.99%) terbinafine recipients were considered as "clinical failure." Tolerability of both preparations was excellent. Despite the limitations of an observer-blind study without microbiological support, the results suggest that once-daily topical sertaconazole is as effective as terbinafine in localized tinea infections.

  16. Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

    Science.gov (United States)

    Charalambous, M; Bhatti, S F M; Van Ham, L; Platt, S; Jeffery, N D; Tipold, A; Siedenburg, J; Volk, H A; Hasegawa, D; Gallucci, A; Gandini, G; Musteata, M; Ives, E; Vanhaesebrouck, A E

    2017-07-01

    Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial.

    Directory of Open Access Journals (Sweden)

    Catriona S Bradshaw

    Full Text Available BACKGROUND: To determine if oral metronidazole (MTZ-400 mg bid with 2% vaginal clindamycin-cream (Clind or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob reduces 6-month bacterial vaginosis (BV recurrence. METHODS: Double-blind placebo-controlled parallel-group single-site study with balanced randomization (1:1:1 conducted at Melbourne Sexual Health Centre, Australia. Participants with symptomatic BV [Nugent Score (NS = 7-10 or ≥3 Amsel's criteria and NS = 4-10], were randomly allocated to MTZ-Clind, MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months. MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days. Primary outcome was BV recurrence (NS of 7-10 on self-collected vaginal-swabs over 6-months. Cumulative BV recurrence rates were compared between groups by Chi-squared statistics. Kaplan-Meier, log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups. RESULTS: 450 18-50 year old females were randomized and 408 (91%, equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9% participants with no post-randomization data were excluded. Six-month retention rates were 78% (n = 351. One-month BV recurrence (NS 7-10 rates were 3.6% (5/140, 6.8% (9/133 and 9.6% (13/135 in the MTZ-Clind, MTZ-Prob and MTZ-Placebo groups respectively, p = 0.13. Hazard ratios (HR for BV recurrence at one-month, adjusted for adherence to vaginal therapy, were 0.43 (95%CI 0.15-1.22 and 0.75 (95% CI 0.32-1.76 in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively. Cumulative 6-month BV recurrence was 28.2%; (95%CI 24.0-32.7% with no difference between groups, p = 0.82; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac, adjusted for adherence to vaginal therapy were 1.09(95% CI = 0.70-1.70 and 1.03(95% CI = 0.65-1.63, respectively. No serious

  18. Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM).

    Science.gov (United States)

    Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

    2018-05-03

    Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. The mean depression change was - 0.66 (95% confidence interval - 2.27 to 0.94) in the active group (n = 80) and - 3.30 (- 4.68 to -1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55-4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by - 1.11 (- 2.16 to - 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (- 0.11 to 6.19), p = 0

  19. Effects of Kivia powder on gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Udani, Jay K; Bloom, David W

    2013-06-08

    To evaluate the efficacy of Kivia powder on supporting overall gut health through the relief of the discomfort of occasional constipation. Randomized, double-blind, placebo-controlled, parallel-group trial. The investigational product for this study was Kivia powder (Vital Food Processors Ltd., Auckland, New Zealand), containing the active ingredient Zyactinase™, 5.5 g taken daily for four weeks. One hundred thirty-eight subjects reporting occasional constipation were screened and 87 were randomized to placebo (n = 44) and product (n = 43). Bowel movement frequency, as measured by both average daily spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM), were the same in both groups at baseline. There were significant increases in spontaneous bowel movements at week 1 (p = 0.001), week 2 (p = 0.001), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. SBM demonstrated significant differences between the treatment group and the placebo group at week 3 (p = 0.000), and week 4 (p = 0.020). The treatment group demonstrated a significantly higher rate of SBM at week 3 (p = 000) and from baseline to week 4 (p = 0.019). Significant increases in complete spontaneous bowel movements were observed at week 1 (p = 0.000), week 2 (p = 0.000), week 3 (p = 0.000), and week 4 (p = 0.000) compared to baseline. Moreover, CSBM was significantly higher for the treatment group compared to placebo at week 2 (p = 0.001). The change in average daily CSBM from baseline to week 2 was significantly higher in the treatment group than in the placebo group (p = 0.004).Abdominal discomfort or pain demonstrated significant differences between groups at week 1 (p = 0.044) and week 3 (p = 0.026). Flatulence was significantly lower for active group compared to placebo at week 2 (p = 0.047) and week 3 (p = 0.023). The number of bowel movements associated with urgency was significantly lower in the treatment group compared to the placebo group at week 3 (p = 0

  20. Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: a double-blind, placebo-controlled, randomized trial.

    Science.gov (United States)

    Ghaleiha, Ali; Mohammadi, Effat; Mohammadi, Mohammad-Reza; Farokhnia, Mehdi; Modabbernia, Amirhossein; Yekehtaz, Habibeh; Ashrafi, Mandana; Hassanzadeh, Elmira; Akhondzadeh, Shahin

    2013-12-01

    A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders. The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications. This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial. The study enrolled male and female outpatients aged 5-12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy. Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks. Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups. Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech

  1. A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults.

    Science.gov (United States)

    Crews, W David; Harrison, David W; Wright, James W

    2008-04-01

    In recent years, there has been increased interest in the potential health-related benefits of antioxidant- and phytochemical-rich dark chocolate and cocoa. The objective of the study was to examine the short-term (6 wk) effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health in healthy older adults. A double-blind, placebo-controlled, fixed-dose, parallel-group clinical trial was used. Participants (n = 101) were randomly assigned to receive a 37-g dark chocolate bar and 8 ounces (237 mL) of an artificially sweetened cocoa beverage or similar placebo products each day for 6 wk. No significant group (dark chocolate and cocoa or placebo)-by-trial (baseline, midpoint, and end-of-treatment assessments) interactions were found for the neuropsychological, hematological, or blood pressure variables examined. In contrast, the midpoint and end-of-treatment mean pulse rate assessments in the dark chocolate and cocoa group were significantly higher than those at baseline and significantly higher than the midpoint and end-of-treatment rates in the control group. Results of a follow-up questionnaire item on the treatment products that participants believed they had consumed during the trial showed that more than half of the participants in both groups correctly identified the products that they had ingested during the experiment. This investigation failed to support the predicted beneficial effects of short-term dark chocolate and cocoa consumption on any of the neuropsychological or cardiovascular health-related variables included in this research. Consumption of dark chocolate and cocoa was, however, associated with significantly higher pulse rates at 3- and 6-wk treatment assessments.

  2. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Rebeccah Slater

    2017-01-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score during the 30 second periods after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  3. Effects of memantine on cognition in patients with moderate to severe Alzheimer's disease: post-hoc analyses of ADAS-cog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studies.

    Science.gov (United States)

    Mecocci, Patrizia; Bladström, Anna; Stender, Karina

    2009-05-01

    The post-hoc analyses reported here evaluate the specific effects of memantine treatment on ADAS-cog single-items or SIB subscales for patients with moderate to severe AD. Data from six multicentre, randomised, placebo-controlled, parallel-group, double-blind, 6-month studies were used as the basis for these post-hoc analyses. All patients with a Mini-Mental State Examination (MMSE) score of less than 20 were included. Analyses of patients with moderate AD (MMSE: 10-19), evaluated with the Alzheimer's disease Assessment Scale (ADAS-cog) and analyses of patients with moderate to severe AD (MMSE: 3-14), evaluated using the Severe Impairment Battery (SIB), were performed separately. The mean change from baseline showed a significant benefit of memantine treatment on both the ADAS-cog (p ADAS-cog single-item analyses showed significant benefits of memantine treatment, compared to placebo, for mean change from baseline for commands (p < 0.001), ideational praxis (p < 0.05), orientation (p < 0.01), comprehension (p < 0.05), and remembering test instructions (p < 0.05) for observed cases (OC). The SIB subscale analyses showed significant benefits of memantine, compared to placebo, for mean change from baseline for language (p < 0.05), memory (p < 0.05), orientation (p < 0.01), praxis (p < 0.001), and visuospatial ability (p < 0.01) for OC. Memantine shows significant benefits on overall cognitive abilities as well as on specific key cognitive domains for patients with moderate to severe AD. (c) 2009 John Wiley & Sons, Ltd.

  4. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  5. A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee

    Directory of Open Access Journals (Sweden)

    Jozef Vojtaššák

    2011-01-01

    Full Text Available Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA. Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.

  6. 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...

  7. The analgesic effect of dexketoprofen when added to lidocaine for intravenous regional anaesthesia: a prospective, randomized, placebo-controlled study.

    Science.gov (United States)

    Yurtlu, S; Hanci, V; Kargi, E; Erdoğan, G; Köksal, B G; Gül, Ş; Okyay, R D; Ayoğlu, H; Turan, I Ö

    2011-01-01

    This prospective, randomized, placebo-controlled study evaluated the effects of dexketoprofen as an adjunct to lidocaine in intravenous regional anaesthesia (IVRA) or as a supplemental intravenous (i.v.) analgesic. Patients scheduled for elective hand or forearm soft-tissue surgery were randomly divided into three groups. All 45 patients received 0.5% lidocaine as IVRA. Dexketoprofen was given either i.v. or added into the IVRA solution and the control group received an equal volume of saline both i.v. and as part of the IVRA. The times of sensory and motor block onset, recovery time and postoperative analgesic consumption were recorded. Compared with controls, the addition of dexketoprofen to the IVRA solution resulted in more rapid onset of sensory and motor block, longer recovery time, decreased intra- and postoperative pain scores and decreased paracetamol use. It is concluded that coadministration of dexketoprofen with lidocaine in IVRA improves anaesthetic block and decreases postoperative analgesic requirements.

  8. Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole

    2017-01-01

    PURPOSE: Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated...... the effect of a vitamin K3 cream on cetuximab-induced rash. MATERIALS AND METHODS: Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream...... stained for EGFR and pEGFR. RESULTS: Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed...

  9. 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...

  10. 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....

  11. A Randomized, Double-Blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue Patients

    Science.gov (United States)

    Nguyen, Nguyet Minh; Tran, Chau Nguyen Bich; Phung, Lam Khanh; Duong, Kien Thi Hue; Huynh, Huy le Anh; Farrar, Jeremy; Nguyen, Quyen Than Ha; Tran, Hien Tinh; Nguyen, Chau Van Vinh; Merson, Laura; Hoang, Long Truong; Hibberd, Martin L.; Aw, Pauline P. K.; Wilm, Andreas; Nagarajan, Niranjan; Nguyen, Dung Thi; Pham, Mai Phuong; Nguyen, Truong Thanh; Javanbakht, Hassan; Klumpp, Klaus; Hammond, Janet; Petric, Rosemary; Wolbers, Marcel; Nguyen, Chinh Tran; Simmons, Cameron P.

    2013-01-01

    Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576. PMID:22807519

  12. Effects of sertindole on cognition in clozapine-treated schizophrenia patients - a double-blinded, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Nielsen, R E; Levander, S; Nielsen, Jimmi

    Nielsen RE, Levander S, Thode D, Nielsen J. Effects of sertindole on cognition in clozapine-treated schizophrenia patients. Objective:  To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial....... Method:  A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. Results:  Participants displayed substantial cognitive deficits......, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative...

  13. 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.

  14. 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...

  15. 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.

  16. A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy subjects

    DEFF Research Database (Denmark)

    Osther, P J; Rasmussen, L; Pedersen, S A

    1992-01-01

    Urinary pH is related to urinary calculus formation as well as urinary infection. Omeprazole is an effective inhibitor of gastric acid secretion through inhibition of the parietal cell H+K+ATPase. In this study we have evaluated a possible effect of omeprazole on urine acidification. Ten healthy...... male subjects took placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo-controlled trial. Morning fasting urinary pH was measured on day 10 of each treatment course using a pH meter. No effect of omeprazole on urinary pH could be demonstrated. It is thus unlikely...... that it is necessary to take omeprazole treatment into consideration in stone screening. As omeprazole did not affect urinary pH, no urological side effects related to changes in urinary pH can be expected....

  17. 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.

  18. 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.

  19. Use of bibloc and monobloc oral appliances in obstructive sleep apnoea: a multicentre, randomized, blinded, parallel-group equivalence trial.

    Science.gov (United States)

    Isacsson, Göran; Nohlert, Eva; Fransson, Anette M C; Bornefalk-Hermansson, Anna; Wiman Eriksson, Eva; Ortlieb, Eva; Trepp, Livia; Avdelius, Anna; Sturebrand, Magnus; Fodor, Clara; List, Thomas; Schumann, Mohamad; Tegelberg, Åke

    2018-05-16

    The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA. To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective. In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea-hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy. Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were -13.8 (95% confidence interval -16.1 to -11.5) in the bibloc group and -12.5 (-14.8 to -10.3) in the monobloc group. The difference of -1.3 (-4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively). The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive. In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude. Registered with Clinical

  20. 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.

  1. Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.

    Science.gov (United States)

    Kuypers, Kim Pc; Dolder, Patrick C; Ramaekers, Johannes G; Liechti, Matthias E

    2017-05-01

    Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

  2. Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    de Oliveira, Ivaldo Jesus Lima; de Souza, Victor Vasconcelos; Motta, Vitor; Da-Silva, Sérgio Leme

    2015-01-01

    Vitamin C ascorbic acid) is a well-known antioxidant that is involved in anxiety, stress, depression, fatigue and mood state in humans. Studies have suggested that oxidative stress may trigger neuropsychological disorders. Antioxidants may play an important therapeutic role in combating the damage caused by oxidative stress in individuals that suffer from anxiety. In this context, it was hypothesized that oral vitamin C supplementation would reduce anxiety. However, few up to date studies have evaluated the consequences of oral vitamin C supplementation on anxiety in humans. The present study examined the effects of oral vitamin C supplements in 42 high school students, in a randomized, double-blind, placebo-controlled trial. The students were given either vitamin C (500 mg day(-1)) or placebo. Plasma concentrations of vitamin C and blood pressure were measured before the intervention and then one day after the intervention. Anxiety levels were evaluated for each student before and after 14 days following supplementation with the Beck Anxiety Inventory. Results showed that vitamin C reduced anxiety levels and led to higher plasma vitamin C concentration compared to the placebo. The mean heart rates were also significantly different between vitamin C group and placebo control group. Present study results not only provide evidence that vitamin C plays an important therapeutic role for anxiety but also point a possible use for antioxidants in the prevention or reduction of anxiety. This suggests that a diet rich in vitamin C may be an effective adjunct to medical and psychological treatment of anxiety and improve academic performance.

  3. The Addition of Platelet-Rich Plasma to Facial Lipofilling: A Double-Blind, Placebo-Controlled, Randomized Trial.

    Science.gov (United States)

    Willemsen, Joep C N; Van Dongen, Joris; Spiekman, Maroesjka; Vermeulen, Karin M; Harmsen, Martin C; van der Lei, Berend; Stevens, H P Jeroen

    2018-02-01

    Lipofilling is a treatment modality to restore tissue volume, but it may also rejuvenate the aging skin. Platelet-rich plasma has been reported to augment the efficacy of lipofilling, both on graft take and rejuvenation, by altering the adipose-derived stem cells. The authors hypothesized that addition of platelet-rich plasma would increase the rejuvenating effect and shorten recovery time. The study conducted was a single-center, double-blind, placebo-controlled, randomized trial (2012 to 2015). In total, a well-defined cohort of 32 healthy female patients enrolled in the study, with 25 completing the follow-up. All patients underwent aesthetic facial lipofilling with either saline or platelet-rich plasma added. Outcome was determined by changes in skin elasticity, volumetric changes of the nasolabial fold, recovery time, and patient satisfaction during follow-up (1 year). Platelet-rich plasma did not improve the outcome of facial lipofilling when looking at skin elasticity improvement, graft volume maintenance in the nasolabial fold. Reversal of the correlation between age and elasticity, however, might suggest a small effect size, and thus might not be significant with our small study population. This randomized, double-blind, placebo-controlled study clearly has shown that platelet-rich plasma significantly reduces postoperative recovery time but does not improve patient outcome when looking at skin elasticity, improvement of the nasolabial fold, or patient satisfaction. The reversal of the correlation between age and elasticity might indicate some effect on skin but requires more power in future studies. Therapeutic, II.

  4. Implementation of a Novel Adherence Monitoring Strategy in a Phase III, Blinded, Placebo-Controlled, HIV-1 Prevention Clinical Trial.

    Science.gov (United States)

    Husnik, Marla J; Brown, Elizabeth R; Marzinke, Mark; Livant, Edward; Palanee-Phillips, Thesla; Hendrix, Craig W; Matovu Kiweewa, Flavia; Nair, Gonasagrie; Soto-Torres, Lydia E; Schwartz, Katie; Hillier, Sharon L; Baeten, Jared M

    2017-11-01

    Placebo-controlled HIV-1 prevention trials of pre-exposure prophylaxis (PrEP) have not generally used concurrent measurement of adherence because of the potential risk of unblinding. However, several pre-exposure prophylaxis trials for HIV-1 prevention among women failed to show effectiveness because of low product adherence. Evaluation of product adherence objectively during a study provides the opportunity for strengthening adherence activities at sites having low adherence. During MTN-020/ASPIRE, a phase III, placebo-controlled trial of the dapivirine intravaginal ring, we implemented an adherence monitoring system. Monitoring began in quarter 1 (Q1) 2013 and continued through the conclusion of the trial. Blood plasma was collected quarterly and tested for dapivirine concentrations while maintaining blinding among study team members involved in participant management. Dapivirine concentrations >95 pg/mL, reflecting >8 hours of continuous use, were assessed as signaling product use. Study leadership monitored results on a monthly basis and provided feedback to site investigators. Experiences were shared across sites to motivate staff and counsel participants to strive toward higher adherence levels. An upward trend in adherence was observed (P dapivirine >95 pg/mL increased from 63% in Q1 2013 to 84% by Q1 2015. Ongoing drug level testing as a marker of adherence in MTN-020/ASPIRE demonstrates the feasibility of real-time adherence monitoring while maintaining study blinding at the level of participants, sites, and study leadership. This approach is novel for large-scale effectiveness studies for HIV-1 prevention.

  5. Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

    Science.gov (United States)

    Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

    2017-07-01

    Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Berk Michael

    2012-08-01

    Full Text Available Abstract Background N-acetyl cysteine (NAC is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149 had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493.

  7. Hemostatic efficacy of TachoSil in liver resection compared with argon beam coagulator treatment: An open, randomized, prospective, multicenter, parallel-group trial

    DEFF Research Database (Denmark)

    Fischer, Lars; Seiler, Christoph M.; Broelsch, Christoph E.

    2011-01-01

    surgical trial with 2 parallel groups. Patients were eligible for intra-operative randomization after elective resection of ≥1 liver segment and primary hemostasis. The primary end point was the time to hemostasis after starting the randomized intervention to obtain secondaty hemostasis. Secondary end...

  8. 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

  9. Reduction of body fat and improved lipid profile associated with daily consumption of a Puer tea extract in a hyperlipidemic population: a randomized placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-03-01

    Full Text Available Gitte S Jensen,1 Joni L Beaman,1 Yi He,2 Zhixin Guo,2 Henry Sun31NIS Labs, Klamath Falls, OR, USA; 2Modern TCM Research Center, Tasly Academy, Tianjin, People’s Republic of China; 3Tasly Pharmaceuticals Inc, Rockville, MD, USA Objective: The goal for this study was to evaluate the effects of daily consumption of Puer tea extract (PTE on body weight, body-fat composition, and lipid profile in a non-Asian population in the absence of dietary restrictions.Materials and methods: A randomized, double-blind, placebo-controlled study design was used. A total of 59 overweight or mildly obese subjects were enrolled upon screening to confirm fasting cholesterol level at or above 220 mg/dL (5.7 mmol/dL. After giving informed consent, subjects were randomized to consume PTE (3 g/day or placebo for 20 weeks. At baseline and at 4-week intervals, blood lipids, C-reactive protein, and fasting blood glucose were evaluated. A dual-energy X-ray absorptiometry scan was performed at baseline and at study exit to evaluate changes to body composition. Appetite and physical and mental energy were scored at each visit using visual analog scales (0–100.Results: Consumption of PTE was associated with statistically significant weight loss when compared to placebo (P<0.05. Fat loss was seen for arms, legs, and the gynoid region (hip/belly, as well as for total fat mass. The fat reduction reached significance on within-group analysis, but did not reach between-group significance. Consumption of PTE was associated with improvements to lipid profile, including a mild reduction in cholesterol and the cholesterol:high-density lipoprotein ratio after only 4 weeks, as well as a reduction in triglycerides and very small-density lipoproteins, where average blood levels reached normal range at 8 weeks and remained within normal range for the duration of the study (P<0.08. No significant changes between the PTE group and the placebo group were seen for fasting glucose or C

  10. A cluster-randomized, placebo-controlled, maternal vitamin a or beta-carotene supplementation trial in bangladesh: design and methods

    Directory of Open Access Journals (Sweden)

    Schulze Kerry

    2011-04-01

    Full Text Available Abstract Background We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field. Methods This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE, beta-carotene (42 mg, or ~7000 ug RE or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies. Results The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and

  11. A cluster-randomized, placebo-controlled, maternal vitamin A or beta-carotene supplementation trial in Bangladesh: design and methods.

    Science.gov (United States)

    Labrique, Alain B; Christian, Parul; Klemm, Rolf D W; Rashid, Mahbubur; Shamim, Abu Ahmed; Massie, Allan; Schulze, Kerry; Hackman, Andre; West, Keith P

    2011-04-21

    We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field. This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies. The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant infectious morbidity

  12. Vitamin D supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults: a randomized placebo-controlled trial.

    Science.gov (United States)

    Mousa, Aya; Naderpoor, Negar; de Courten, Maximilian Pj; Teede, Helena; Kellow, Nicole; Walker, Karen; Scragg, Robert; de Courten, Barbora

    2017-06-01

    Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion. Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo. Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)]. Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m 2 ): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg -1 · min -1 , respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex

  13. Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Mulligan, Kathleen; Glidden, David V.; Anderson, Peter L.; Liu, Albert; McMahan, Vanessa; Gonzales, Pedro; Ramirez-Cardich, Maria Esther; Namwongprom, Sirianong; Chodacki, Piotr; de Mendonca, Laura Maria Carvalo; Wang, Furong; Lama, Javier R.; Chariyalertsak, Suwat; Guanira, Juan Vicente; Buchbinder, Susan; Bekker, Linda-Gail; Schechter, Mauro; Veloso, Valdilea G.; Grant, Robert M.; Vargas, Lorena; Sanchez, Jorge; Mai, Chiang; Saokhieo, Pongpun; Murphy, Kerry; Gilmore, Hailey; Holland, Sally; Faber, Elizabeth; Duda, John; Bewerunge, Linda; Batist, Elizabeth; Hoskin, Christine; Brown, Ben; de Janeiro, Rio; Beppu-Yoshida, Carina; da Costa, Marcellus Dias; Assis de Jesus, Sergio Carlos; Grangeiro da Silva, Jose Roberto; Millan, Roberta; de Siqueira Hoagland, Brenda Regina; Martinez Fernandes, Nilo; da Silva Freitas, Lucilene; Grinsztejn, Beatriz; Pilotto, Jose; Bushman, Lane; Zheng, Jia-Hua; Anthony Guida, Louis; Kline, Brandon; Goicochea, Pedro; Manzo, Jonathan; Hance, Robert; McConnell, Jeff; Defechereux, Patricia; Levy, Vivian; Robles, Malu; Postle, Brian; Burns, David; Rooney, James

    2015-01-01

    Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, −0.91% [95% confidence interval {CI}, −1.44% to −.38%]; P = .001) and hip (−0.61% [95% CI, −.96% to −.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged −1.42% ± 29% and −0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. Clinical Trials Registration. NCT00458393. PMID:25908682

  14. Treatment with Creatine Monohydrate in Spinal and Bulbar Muscular Atrophy: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Hijikata, Yasuhiro; Katsuno, Masahisa; Suzuki, Keisuke; Hashizume, Atsushi; Araki, Amane; Yamada, Shinichiro; Inagaki, Tomonori; Ito, Daisuke; Hirakawa, Akihiro; Kinoshita, Fumie; Gosho, Masahiko; Sobue, Gen

    2018-03-05

    Although spinal and bulbar muscular atrophy (SBMA) has been classified as a motor neuron disease, several reports have indicated the primary involvement of skeletal muscle in the pathogenesis of this devastating disease. Recent studies reported decreased intramuscular creatine levels in skeletal muscles in both patients with SBMA and transgenic mouse models of SBMA, which appears to contribute to muscle weakness. The present study aimed to examine the efficacy and safety of oral creatine supplementation to improve motor function in patients with SBMA. A randomized, double-blind, placebo-controlled, three-armed clinical trial was conducted to assess the safety and efficacy of creatine therapy in patients with SBMA. Patients with SBMA eligible for this study were assigned randomly in a 1:1:1 ratio to each group of placebo, 10 g, or 15 g daily dose of creatine monohydrate in a double-blind fashion. Participants took creatine or placebo orally 3 times a day for 8 weeks. Outcome measurements were results of neurological assessments, examinations, and questionnaires collected at baseline and at weeks 4, 8, and 16 after a washout period. The primary endpoint was the change in handgrip strength values from baseline to week 8. The secondary endpoints included the following: results of maximum voluntary isometric contraction tests of extremities; tongue pressure; results of the 15-foot timed walk test and the rise from bed test; modified quantitative myasthenia gravis score; respiratory function test results; activities of daily living assessed with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale and the Spinal and Bulbar Muscular Atrophy Functional Rating Scale; skeletal muscle mass measured with dual-energy X-ray absorptiometry; urinary 8-hydroxydeoxyguanosine levels; and questionnaires examining the quality of life, swallowing function, and fatigue. Participant enrollment in the trial started from June 2014 and follow-up was completed in July 2015. The

  15. Consumption of extra virgin olive oil improves body composition and blood pressure in women with excess body fat: a randomized, double-blinded, placebo-controlled clinical trial.

    Science.gov (United States)

    Galvão Cândido, Flávia; Xavier Valente, Flávia; da Silva, Laís Emilia; Gonçalves Leão Coelho, Olívia; Gouveia Peluzio, Maria do Carmo; Gonçalves Alfenas, Rita de Cássia

    2017-08-14

    Despite the fact that extra virgin olive oil (EVOO) is widely used in obese individuals to treat cardiovascular diseases, the role of EVOO on weight/fat reduction remains unclear. We investigated the effects of energy-restricted diet containing EVOO on body composition and metabolic disruptions related to obesity. This is a randomized, double-blinded, placebo-controlled clinical trial in which 41 adult women with excess body fat (mean ± SD 27.0 ± 0.9 year old, 46.8 ± 0.6% of total body fat) received daily high-fat breakfasts containing 25 mL of soybean oil (control group, n = 20) or EVOO (EVOO group, n = 21) during nine consecutive weeks. Breakfasts were part of an energy-restricted normal-fat diets (-2090 kJ, ~32%E from fat). Anthropometric and dual-energy X-ray absorptiometry were assessed, and fasting blood was collected on the first and last day of the experiment. Fat loss was ~80% higher on EVOO compared to the control group (mean ± SE: -2.4 ± 0.3 kg vs. -1.3 ± 0.4 kg, P = 0.037). EVOO also reduced diastolic blood pressure when compared to control (-5.1 ± 1.6 mmHg vs. +0.3 ± 1.2 mmHg, P = 0.011). Within-group differences (P group, and for serum creatinine (+0.04 ± 0.01 µmol/L) and alkaline phosphatase (-3.3 ± 1.8 IU/L) in the EVOO group. There was also a trend for IL-1β EVOO reduction (-0.3 ± 0.1 pg/mL, P = 0.060). EVOO consumption reduced body fat and improved blood pressure. Our results indicate that EVOO should be included into energy-restricted programs for obesity treatment.

  16. 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…

  17. The effects of alcohol mixed with energy drink (AMED) on subjective intoxication and alertness : results from a double-blind placebo-controlled clinical trial

    NARCIS (Netherlands)

    van de Loo, Aurora J A E; van Andel, Nienke; van Gelder, Charlotte A G H; Janssen, Boris S G; Titulaer, Joep; Jansen, Jimmy; Verster, Joris C

    2016-01-01

    OBJECTIVE: The purpose of this double blind placebo controlled study was to examine if specific effects on subjective intoxication and alertness-sleepiness ratings could be demonstrated after consuming alcohol mixed with energy drink (AMED) when compared to consuming alcohol only (AO). METHODS: 56

  18. NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

    NARCIS (Netherlands)

    Lawlor, B.; Kennelly, S.; O'Dwyer, S.; Cregg, F.; Walsh, C.; Coen, R.; Kenny, R.A.; Howard, R.; Murphy, C.; Adams, J.; Daly, L.; Segurado, R.; Gaynor, S.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Wallin, A.; Borjesson, A.; Molloy, W.; Tsolaki, M.; Olde Rikkert, M.G.M.

    2014-01-01

    INTRODUCTION: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82

  19. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial on psychological distress

    NARCIS (Netherlands)

    Aarab, Ghizlane; Nikolopoulou, Maria; Ahlberg, Jari; Heymans, Martijn W.; Hamburger, Hans L.; de Lange, Jan; Lobbezoo, Frank

    2017-01-01

    The aim of this randomized placebo-controlled trail was to compare the effects of an objectively titrated mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) and an intraoral placebo device on symptoms of psychological distress in OSA patients. In a

  20. Laxation of critically ill patients with lactulose or polyethylene glycol : a two-center randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    van der Spoel, Johan I; Oudemans-van Straaten, Heleen M; Kuiper, Michael A; van Roon, Eric N; Zandstra, Durk F; van der Voort, Peter H J

    2007-01-01

    OBJECTIVE: To study whether lactulose or polyethylene glycol is effective to promote defecation in critically ill patients, whether either of the two is superior, and whether the use of enteral laxatives is related to clinical outcome. DESIGN: Double-blind, placebo-controlled, randomized study.

  1. Efficacy and safety of statin therapy in children with familial hypercholesterolemia - A randomized, double-blind, placebo-controlled trial with simvastatin

    NARCIS (Netherlands)

    de Jongh, Saskia; Ose, Leiv; Szamosi, Tamás; Gagné, Claude; Lambert, M.; Scott, Russell; Perron, P.; Dobbelaere, Dries; Saborio, M.; Tuohy, Mary B.; Stepanavage, Michael; Sapre, Aditi; Gumbiner, Barry; Mercuri, Michele; van Trotsenburg, A. S. Paul; Bakker, Henk D.; Kastelein, John J. P.

    2002-01-01

    Background-A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous

  2. Treatment of Patients With Complex Regional Pain Syndrome Type I With Mannitol: A Prospective, Randomized, Placebo-Controlled, Double-Blinded Study

    NARCIS (Netherlands)

    Perez, R.S.G.M.; Pragt, E.; Geurts, J.J.G.; Zuurmond, W.W.A.; Patijn, J.; van Kleef, M.

    2008-01-01

    To assess the effects of intravenous administration of the free radical scavenger mannitol 10% on complaints associated with complex regional pain syndrome Type I (CRPS I), a randomized, placebo-controlled, double-blinded trial was performed. Forty-one CRPS I patients according to the Bruehl et al

  3. Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial

    NARCIS (Netherlands)

    Martinez de Tejada, B.; Karolinski, A.; Ocampo, M. C.; Laterra, C.; Hösli, I.; Fernández, D.; Surbek, D.; Huespe, M.; Drack, G.; Bunader, A.; Rouillier, S.; López de Degani, G.; Seidenstein, E.; Prentl, E.; Antón, J.; Krähenmann, F.; Nowacki, D.; Poncelas, M.; Nassif, J. C.; Papera, R.; Tuma, C.; Espoile, R.; Tiberio, O.; Breccia, G.; Messina, A.; Peker, B.; Schinner, E.; Mol, B. W.; Kanterewicz, L.; Wainer, V.; Boulvain, M.; Othenin-Girard, V.; Bertolino, M. V.; Irion, O.; Tellenbach, M.; Vögele, E.; Azbar, R.; Raggi, A.; Birkenmaier, A.; Kann, S.; Scheibner, K.; Huguelet, M.; Amann, E.; Baumann, M.; Jakob, E.; Biedermann, K.; Hodel, M.; Fischer, T.; Pfau, K.; Estermann, K.

    2015-01-01

    To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. Multicentre, randomised, double-blind, placebo-controlled trial. Twenty-nine centres in Switzerland and Argentina. A total of 385 women with preterm labour (24(0/7) to

  4. RETRACTED: Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomized, double-blind, placebo-controlled, dose-ranging study

    Directory of Open Access Journals (Sweden)

    MD Yoshitaka Fujii

    2004-07-01

    Fujii Y, Tanaka H, Somekawa Y. Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomised, double-blind, placebo-controlled, dose-ranging study. Current Therapeutic Research 2004;65:321–9. https://www.sciencedirect.com/science/article/pii/S0011393X04800018

  5. The effect of barusiban, a selective oxytocin antagonist, in threatened preterm labor at late gestational age: a randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Thornton, Steven; Goodwin, Thomas M; Greisen, Gorm

    2009-01-01

    OBJECTIVE: The objective of the study was to compare barusiban with placebo in threatened preterm labor. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled, multicenter study. One hundred sixty-three women at 34-35 weeks plus 6 days, and with 6 or more contractions of 30 seconds...

  6. 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…

  7. Vitamin D3 supplementation increases spine bone mineral density in adolescents and young adults with HIV infection being treated with tenofovir disoproxil fumarate: a randomized, placebo controlled trial

    Science.gov (United States)

    Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in adolescents/young adults receiving TDF. Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 50,000 IU vs. placebo every 4 ...

  8. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; Koester, Juergen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

    2005-01-01

    Objective To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized

  9. The angiotensin II receptor antagonist telmisartan reduces urinary albumin excretion in patients with isolated systolic hypertension: results of a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Vogt, Liffert; Navis, Gerjan; Köster, Jürgen; Manolis, Athanasios J.; Reid, John L.; de Zeeuw, Dick

    2005-01-01

    To examine the effect of telmisartan or hydrochlorothiazide on the control of urinary albumin excretion (UAE) in patients with isolated systolic hypertension (ISH) unselected for albuminuria in a pre-planned substudy of a large, multicentre, double-blind, placebo-controlled, randomized study. The

  10. 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...

  11. Effect of perioperative beta blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

    DEFF Research Database (Denmark)

    Juul, Anne Benedicte; Wetterslev, Jørn; Gluud, Christian

    2006-01-01

    Objectives To evaluate the long term effects of perioperative blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University...

  12. Randomized, Placebo-Controlled Phase 2 Trial of a Lactobacillus crispatus Probiotic Given Intravaginally for Prevention of Recurrent Urinary Tract Infection

    OpenAIRE

    Stapleton, Ann E.; Au-Yeung, Melissa; Hooton, Thomas M.; Fredricks, David N.; Roberts, Pacita L.; Czaja, Christopher A.; Yarova-Yarovaya, Yuliya; Fiedler, Tina; Cox, Marsha; Stamm, Walter E.

    2011-01-01

    In a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (LACTIN-VÜ, Osel, Inc.) for prevention of recurrent UTI (rUTI) in pre-menopausal women, LACTIN-V was safe, well tolerated, and associated with a reduction in rUTI.

  13. Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko

    2008-01-01

    OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with

  14. 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...

  15. Melatonin Improves Health Status and Sleep in Children With Idiopathic Chronic Sleep-Onset Insomnia: A Randomized Placebo-Controlled Trial

    NARCIS (Netherlands)

    Smits, M.G.; Stel, H.F. van; Heijden, K.B. van der; Meijer, A.M.; Coenen, A.M.L.; Kerkhof, G.A.

    2003-01-01

    Objective: To investigate the effect of melatonin treatment on health status and sleep in children with idiopathic sleep-onset insomnia. Method: A randomized, double-blind, placebo-controlled trial was conducted in a Dutch sleep center, involving 62 children, 6 to 12 years of age, who suffered more

  16. RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF PATIENTS WITH SEPSIS SYNDROME - RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

    NARCIS (Netherlands)

    FISHER, C. J.; DHAINAUT, J. F. A.; Opal, S. M.; Pribble, J. P.; BALK, R. A.; SLOTMAN, G. J.; IBERTI, T. J.; RACKOW, E. C.; SHAPIRO, M. J.; GREENMAN, R. L.; REINES, H. D.; SHELLY, M. P.; THOMPSON, B. W.; LABRECQUE, J. F.; Catalano, M. A.; KNAUS, W. A.; Sadoff, J. C.; ASTIZ, M.; CARPATI, C.; BONE, R. C.; FREIDMAN, B.; MURE, A. J.; BRATHWAITE, C.; SHAPIRO, E.; MELHORN, L.; TAYLOR, R.; KEEGAN, M.; OBRIEN, J.; SCHEIN, R.; PENA, M.; WASSERLOUF, M.; OROPELLO, J.; BENJAMIN, E.; DELGUIDICE, R.; EMMANUEL, G.; LIE, T.; Anderson, L.; Marshall, J.; DEMAJO, W.; ROTSTEIN, O.; FOSTER, D.; Abraham, E.; MIDDLETON, H.; Perry, C.; LEVY, H.; FRY, D. E.; SIMPSON, S. Q.; CROWELL, R. E.; Neidhart, M.; Stevens, D.; COFFMAN, T.; NARASIMHAM, N.; MERRICK, D. K.; BERGQUIST, W.; MATZEL, K. E.; HUEBLER, M.; Foulke, G. E.; ALBERTSON, T. E.; WALBY, W. F.; ALLEN, R. P.; Baughman, R.; HASSELGREN, P. O.; Fink, M. P.; FAVORITO, F.; THOMPSON, B. T.; CORBIN, R.; SHELLHORSE, G. Y.; FRAZIER, A.; White, S.; GARRARD, C.; ACOURT, C.; STORER, S.; GERVICH, D. H.; FOSHE, D.; BRASE, R.; BAGDAHN, A.; COONEY, R.; Smith, J. S.; MARTIN, L. F.; Vincent, J. L.; Friedman, G.; Berlot, G.; FLETCHER, J. R.; WILLIAMS, M. D.; WRIGHT, T. F.; Johnson, S.; FEILD, C.; WOLF, K.; MACINTYRE, N.; DUBIN, H. G.; DURKIN, M. R.; DUBIN, P. K.; STAUBACH, K. H.; FEIN, A. M.; SCHULMAN, D. B.; NIEDERMAN, M. S.; CHALFIN, D. B.; van Leeuwen, P. A. M.; Boermeester, M. A.; Schneider, A. J.; BANDER, J.; IMM, A.; BERNARD, G.; Nelson, L.; Stroud, M.; SAFCSAK, K.; CERRA, F.; RINDAL, J.; Mann, H.; HALPERN, N.; SILVERSTEIN, J.; ALICEA, M.; Sibbald, W. J.; MARTIN, C. M.; RUTLEDGE, F. S.; PETTI, K.; RUSSELL, J. A.; KRUGER, R.; DRUMMOND, A.; LANGE, P.; SEIFERT, T.; DUROCHER, A.; TENAILLON, A.; BOITEAU, R.; LHERM, T.; Lowry, S. F.; Coyle, S. M.; Barie, P. S.; DEMARIA, E.; SNYDMAN, D. R.; SCHWAITZBERG, S. D.; NASRAWAY, S. A.; GRINDLINGER, J.; SUMMER, W.; DEBOISBLANC, B.; WAHL, M.; ALESTIG, K.; GROSSMAN, J.; MAKI, D.; PAZ, H. L.; Weiner, M.; BIHARI, D.; Campbell, D.; BLEICHNER, G.; DAHN, M. S.; LANGE, M. P. A.; Hall, J.; POHLMAN, A.; WENZEL, R. P.; GROSSERODE, M.; COSTIGAN, M.; MILESKI, W.; WEIGELT, J.; YESTON, N.; IRIZARRY, C.; Ross, J.; ROBBINS, J.; NIGHTINGALE, P.; OWEN, K.; SANDSTEDT, S.; Berg, S.; SIMON, G. L.; SENEFF, M. G.; CONRY, K. M.; ZIMMERMAN, J. L.; Dellinger, R. P.; Johnston, R.; ALLEE, P.; GRANDE, P. O.; MYHRE, E.; DHAINAUT, J. F.; HAMY, I.; Mira, J. P.; HARMON, J.; White, J.; MCKIE, L.; SILVERMAN, H.; TUMA, P.; Bennett, D.; PORTER, J. C.; LAURELL, M. H.; Jacobs, S.; ASH, S.; Stiles, D. M.; PRIOR, M. J.; KNATTERUD, G.; TERRIN, M.; KUFERA, J.; WILKENS, P.; RA, K.; MONROE, L.; SPRUNG, C.; HAMILTON, C. M.; MATTHAY, R.; MCCABE, W.; TONASCIA, J.; WIEDEMAN, H.; Wittes, J.; CAMPION, G. V.; CROFT, C. R.; LUSTICK, R.; LOOKABAUGH, J.; GORDON, G. S.; NOE, L.; BLOEDOW, D.; SMITH, C. G.; BRANNON, D.; KUSH, R.; NG, D.; MOORE, E.; BAZEMORE, K.; GALVAN, M.; Wagner, D.; HARRELL, F.; STABLEIN, D.

    1994-01-01

    Objective.-To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhlL-1ra) in the treatment of sepsis syndrome. Study Design.-Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. Population.-A total of 893 patients with

  17. 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

  18. Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

    2017-02-01

    Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

  19. Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Steven F L van Lelyveld

    Full Text Available The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4+ T-cell counts and immune activation in these patients.Double-blind, placebo-controlled, randomized trial.Major inclusion criteria were 1. CD4+ T-cell count <350 cells/μL while at least two years on cART or CD4+ T-cell count <200 cells/μL while at least one year on cART, and 2. viral suppression for at least the previous 6 months. HIV-infected patients were randomized to add maraviroc (41 patients or placebo (44 patients to their cART regimen for 48 weeks. Changes in CD4+ T-cell counts (primary endpoint and other immunological parameters were modeled using linear mixed effects models.No significant differences for the modelled increase in CD4+ T-cell count (placebo 15.3 CD4+ T cells/μL (95% confidence interval (CI [1.0, 29.5] versus maraviroc arm 22.9 CD4+ T cells/μL (95% CI [7.4, 38.5] p = 0.51 or alterations in the expression of markers for T-cell activation, proliferation and microbial translocation were found between the arms. However, maraviroc intensification did increase the percentage of CCR5 expressing CD4+ and CD8+ T-cells, and the plasma levels of the CCR5 ligand MIP-1β. In contrast, the percentage of ex-vivo apoptotic CD8+ and CD4+ T-cells decreased in the maraviroc arm.Maraviroc intensification of cART did not increase CD4+ T-cell restoration or decrease immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was decreased in the maraviroc arm.ClinicalTrials.gov NCT00875368.

  20. Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial.

    Science.gov (United States)

    Hannemann, Pascal; Göttgens, Kevin W A; van Wely, Bob J; Kolkman, Karel A; Werre, Andries J; Poeze, Martijn; Brink, Peter R G

    2011-05-06

    The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences.Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning).Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory.Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional

  1. Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

    Directory of Open Access Journals (Sweden)

    Poeze Martijn

    2011-05-01

    Full Text Available Abstract Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%, non-union (5-21% and early osteo-arthritis (up to 32% which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning. Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation

  2. Critical appraisal of arguments for the delayed-start design proposed as alternative to the parallel-group randomized clinical trial design in the field of rare disease.

    Science.gov (United States)

    Spineli, Loukia M; Jenz, Eva; Großhennig, Anika; Koch, Armin

    2017-08-17

    A number of papers have proposed or evaluated the delayed-start design as an alternative to the standard two-arm parallel group randomized clinical trial (RCT) design in the field of rare disease. However the discussion is felt to lack a sufficient degree of consideration devoted to the true virtues of the delayed start design and the implications either in terms of required sample-size, overall information, or interpretation of the estimate in the context of small populations. To evaluate whether there are real advantages of the delayed-start design particularly in terms of overall efficacy and sample size requirements as a proposed alternative to the standard parallel group RCT in the field of rare disease. We used a real-life example to compare the delayed-start design with the standard RCT in terms of sample size requirements. Then, based on three scenarios regarding the development of the treatment effect over time, the advantages, limitations and potential costs of the delayed-start design are discussed. We clarify that delayed-start design is not suitable for drugs that establish an immediate treatment effect, but for drugs with effects developing over time, instead. In addition, the sample size will always increase as an implication for a reduced time on placebo resulting in a decreased treatment effect. A number of papers have repeated well-known arguments to justify the delayed-start design as appropriate alternative to the standard parallel group RCT in the field of rare disease and do not discuss the specific needs of research methodology in this field. The main point is that a limited time on placebo will result in an underestimated treatment effect and, in consequence, in larger sample size requirements compared to those expected under a standard parallel-group design. This also impacts on benefit-risk assessment.

  3. 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.

  4. Short-Term Effect of Laser Acupuncture on Lower Back Pain: A Randomized, Placebo-Controlled, Double-Blind Trial

    Directory of Open Access Journals (Sweden)

    Jae-Young Shin

    2015-01-01

    Full Text Available Purpose. This trial was performed to investigate the efficacy of laser acupuncture for the alleviation of lower back pain. Methods. This was a randomized, placebo-controlled, double-blind trial. Fifty-six participants were randomly assigned to either the laser acupuncture group (n=28 or the sham laser acupuncture group (n=28. Participants in both groups received three treatment sessions over the course of one week. Thirteen acupuncture points were selected. The visual analogue scale for pain, pressure pain threshold, Patient Global Impression of Change, and Euro-Quality-of-Life Five Dimensions questionnaire (Korean version were used to evaluate the effect of laser acupuncture treatment on lower back pain. Results. There were no significant differences in any outcome between the two groups, although the participants in both groups showed a significant improvement in each assessed parameter relative to the baseline values. Conclusion. Although there was no significant difference in outcomes between the two groups, the results suggest that laser acupuncture can provide effective pain alleviation and can be considered an option for relief from lower back pain. Further studies using long-term intervention, a larger sample size, and rigorous methodology are required to clarify the effect of laser acupuncture on lower back pain.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Randomized, double-blind, placebo-controlled trial of saw palmetto in men with lower urinary tract symptoms.

    Science.gov (United States)

    Gerber, G S; Kuznetsov, D; Johnson, B C; Burstein, J D

    2001-12-01

    To assess the effects of saw palmetto on urinary symptoms, sexual function, and urinary flow rate in men with lower urinary tract symptoms using a double-blind, randomized, placebo-controlled trial. The eligible patients were 45 years of age or older and had an International Prostate Symptom Score of 8 or greater. After a 1-month placebo run-in period, 85 men were randomized to receive saw palmetto or placebo for 6 months. Patients were evaluated using the International Prostate Symptom Score, a sexual function questionnaire, and by measurement of the urinary flow rate. The mean symptom score decreased from 16.7 to 12.3 in the saw palmetto group compared with 15.8 to 13.6 in the placebo group (P = 0.038). The quality-of-life score improved to a greater degree in the saw palmetto group, but this difference was not statistically significant. No change occurred in the sexual function questionnaire results in either group. The peak flow rate increased by 1.0 mL/s and 1.4 mL/s in the saw palmetto and placebo groups, respectively (P = 0.73). Saw palmetto led to a statistically significant improvement in urinary symptoms in men with lower urinary tract symptoms compared with placebo. Saw palmetto had no measurable effect on the urinary flow rates. The mechanism by which saw palmetto improves urinary symptoms remains unknown.

  10. Are postoperative intravenous antibiotics necessary after bimaxillary orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Tan, S K; Lo, J; Zwahlen, R A

    2011-12-01

    Postoperative antibiotic prophylaxis is often administered intravenously, despite an increased morbidity rate compared with oral application. This study investigates whether a postoperative oral antibiotic regimen is as effective as incorporation of intravenous antibiotics after bimaxillary orthognathic surgery. 42 patients who underwent bimaxillary orthognathic surgery between December 2008 and May 2010 were randomly allocated to 2 placebo-controlled postoperative antibiotic prophylaxis groups. Group 1 received oral amoxicillin 500mg three times daily; group 2 received intravenous ampicillin 1g four times daily, during the first two postoperative days. Both groups subsequently took oral amoxicillin for three more days. Clinically, the infection rate was assessed in both study groups for a period of 6 weeks after the surgery. 9 patients (21.4%) developed infection. No adverse drug event was detected. No significant difference (p=0.45) was detected in the infection rate between group 1 (3/21) and group 2 (6/21). Age, type of surgical procedures, duration of the operative procedure, surgical procedure-related events, blood loss, and blood transfusion were all found not related to infection (p>0.05). Administration of more cost-effective oral antibiotic prophylaxis, which causes less comorbidity, can be considered to be safe in bimaxillary orthognathic surgery with segmentalizations. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. Placebo-controlled phase II study of vitamin K3 cream for the treatment of cetuximab-induced rash.

    Science.gov (United States)

    Eriksen, Jesper Grau; Kaalund, Inger; Clemmensen, Ole; Overgaard, Jens; Pfeiffer, Per

    2017-07-01

    Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated the effect of a vitamin K3 cream on cetuximab-induced rash. Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m 2 every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream and placebo were applied twice daily on two separate areas of the skin of minimum 10 × 10 cm for up to 2 months. Papulopustular eruptions were evaluated clinically and monitored by clinical photos. Skin biopsies, from ten patients taken before and after 1 month of treatment from each treatment area, were stained for EGFR and pEGFR. Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed in the skin of the vitamin K3-treated area compared to the placebo area. The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash.

  12. Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: A randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Andresen, Sven R; Bing, Jette; Hansen, Rikke Bod Middelhede

    2016-01-01

    , double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment...... with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation...... included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (-0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity...

  13. Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults.

    Science.gov (United States)

    Vlieg-Boerstra, B J; Herpertz, I; Pasker, L; van der Heide, S; Kukler, J; Jansink, C; Vaessen, W; Beusekamp, B J; Dubois, A E J

    2011-07-01

    In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume. Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test. For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs. All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children. © 2011 John Wiley & Sons A/S.

  14. Double-blind, placebo-controlled pilot study of adjunctive quetiapine SR in the treatment of PMS/PMDD.

    Science.gov (United States)

    Jackson, Christine; Pearson, Brenda; Girdler, Susan; Johnson, Jacqueline; Hamer, Robert M; Killenberg, Susan; Meltzer-Brody, Samantha

    2015-11-01

    Premenstrual dysphoric disorder (PMDD), a more severe form of premenstrual syndrome (PMS), afflicts 5-8% of reproductive age women and results in significant functional impairment. We conducted a double-blind, placebo-controlled trial of adjunctive quetiapine in patients with PMS/PMDD who had inadequate response to selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy for their symptoms. A PMS/PMDD diagnosis was confirmed by 2-month prospective diagnostic assessment of PMS/PMDD using the Prospective Record of the Impact and Severity of Premenstrual Symptoms (PRISM) calendar. Women were randomized equally to receive quetiapine sustained-release (SR) or placebo (25-mg starting dose) during the luteal phase for 3 months. Outcome variables included the Hamilton Depression and Anxiety Scales, Clinical Global Impression Scale, and PRISM. Twenty women were enrolled in the treatment phase. Although the study was underpowered, greater reductions in luteal phase mood ratings were observed in the quetiapine group on the 17-item Hamilton Depression Rating Scale, Clinical Global Impression improvement rating, and PRISM daily score. The quetiapine group showed most improvement in symptoms of mood lability, anxiety, and irritability. This small double-blind study suggests that adjunctive treatment with quetiapine SR may be a useful addition to selective serotonin reuptake inhibitor therapy in women with PMS/PMDD by reducing symptoms and improving quality of life. Copyright © 2015 John Wiley & Sons, Ltd.

  15. 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.

  16. Aspirin desensitization for patients with aspirin-exacerbated respiratory disease: A randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Esmaeilzadeh, Hossein; Nabavi, Mohammad; Aryan, Zahra; Arshi, Saba; Bemanian, Mohammad Hassan; Fallahpour, Morteza; Mortazavi, Negar

    2015-10-01

    The effect of aspirin desensitization (AD) on immunologic profile of patients with AERD has been poorly understood. This study is aimed at investigating the effect of AD on clinical and immunological markers of patients with AERD. This randomized double-blind placebo-controlled trial comprised 34 adult patients (67.6% female) with chronic rhinosinusitis, nasal polyps, and aspirin-intolerant asthma. The active group underwent AD over a 2-day period with increasing doses of aspirin (60, 125, 325, and 625 mg), followed by receiving aspirin 625 mg twice daily for 6 months. Symptom scores and medication needs of patients with AERD who have undergone AD were significantly lower compared to the placebo group after 6 months (7.5 ± 3.5 vs. 10.6 ± 3.8 and 9.3 ± 2.0 vs. 11.0 ± 3.1, respectively, all p < 0.05). However, no significant difference was observed in serum concentration of IL-10, IFN-γ, and TGF-β between two groups neither at baseline nor at the end of study. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. 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...

  18. Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Andrew Scholey

    2017-02-01

    Full Text Available Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6, in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171 were randomized (1:1 to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.

  19. 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.

  20. Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Ghaleiha, Ali; Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Shahei, Maryam; Tabrizi, Mina; Hajiaghaee, Reza; Hassanzadeh, Elmira; Akhondzadeh, Shahin

    2013-05-01

    Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).

  1. Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Rezaei, Farzin; Ghaderi, Ebrahim; Mardani, Roya; Hamidi, Seiran; Hassanzadeh, Kambiz

    2016-06-01

    To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P methamphetamine dependence. © 2016 Société Française de Pharmacologie et de Thérapeutique.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Acupuncture for serum uric acid in patients with asymptomatic hyperuricemia: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Huang, Yingjuan; Meng, Jun; Sun, Baoguo; Xiang, Ting; Zhou, Xin; Xu, Biyu; Wu, Yingzi; Chen, Zexiong; Zhang, Shijun

    2017-04-01

    Hyperuricemia (HUA) is the most common disease associated with cardiovascular disease, metabolic syndrome, hypertension, and kidney disease. The objective of the current study was to evaluate the preliminary efficacy, mechanism, and safety of acupuncture on serum uric acid in patients with asymptomatic HUA. A randomized, placebo-controlled trial among 123 patients with asymptomatic HUA was conducted. The acupoints used in the acupuncture group were bilateral Five Shu in Spleen Meridian. Each participant received the intervention once daily for 10 consecutive days. The sham group received the same treatment duration on the same acupoints by the Park Sham Device. All patients underwent measurements of serum or urine creatinine, uric acid, serum lipid profiles, fasting plasma glucose, HbA1c, xanthine oxidase (XOD) and urate-anion exchanger (URAT-1). At the end of the intervention, the individuals in the acupuncture group were found to have significantly less levels of serum uric acid than those in the sham group [(453±65 vs. 528±81) μmol/L, puric acid level, urine pH value and 24-hour urine volume than the sham treatment (puric acid in a Chinese HUA patient population. The mechanism might be associated with the decrease level of enzyme URAT-1. ChiCTR-TRC-13004122. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Zinc Sulfate: An Effective Micronutrient for Common Colds in Children: A Double-Blind Placebo Controlled Trial

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    Mehdi Gholamzadeh Baeis

    2017-10-01

    Full Text Available Background Cold is defined as a viral infection of the upper respiratory tract. The disease is more common in children than in adults and usually requires greater attention and care. Methods This double-blind randomized placebo-controlled trial (zinc versus placebo of zinc was carried out using a repeated measures design. After excluding the cases that met the exclusion criteria, data was collected from 120 participants and analyzed. The study was conducted over a period of 3 months (June 2015 to August 2015. The intervention group received Zinc (1 mg/kg for 7 days and the control group received the same amount of placebo. Results The durations of runny nose and nasal congestion was significantly shorter in patients in the intervention group, who had received zinc, when compared with the control group (P = 0.017 and P = 0.001, respectively. Moreover, there were significant differences between patients, who received zinc and those, who did not receive the drug, in terms of the duration, severity of signs and symptoms, severity of illness, and weakness (P = 0.018. Conclusions Based on the results of this study and other similar studies, zinc sulfate has positive effects on children with colds. Thus, the results of these studies could be utilized by medical teams to adopt a more accurate and complete clinical approach towards the use of zinc sulfate for patients with colds.

  5. 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.

  6. Randomized, Double-Blind, and Placebo-Controlled Clinic Report of Intranasal Low-Intensity Laser Therapy on Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2012-01-01

    Full Text Available The intranasal low intensity GaInP/AlGaInP diode 650 nm laser therapy (ILGLT might improve blood lipid and hemorheologic behavior of patients in view of its previous research, but it should be further supported by a randomized, double-blind, and placebo-controlled clinical study. In this paper, 90 patients with coronary heart disease or cerebral infarction were randomly divided into two groups, 60 in the treatment group and 30 in the control group, and were blindly treated with ILGLT at 8.38 and 0 mW/cm2 for 30 min each time once a day ten days each session for two sessions between which there were three days for rest, respectively. Fasting blood lipid such as total cholesterol and low/high-density lipoprotein cholesterol and hemorheologic behavior such as blood viscosity, plasma viscosity, redox viscosity and red blood cell aggregation were assessed before the first treatment and after the two sessions and were found to be significantly improved by ILGLT. It was concluded that ILGLT may improve blood lipid and hemorheologic behavior of patients with coronary heart disease or cerebral infarction.

  7. A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum.

    Science.gov (United States)

    Hale, Braden R; Owusu-Agyei, Seth; Fryauff, David J; Koram, Kwadwo A; Adjuik, Martin; Oduro, Abraham R; Prescott, W Roy; Baird, J Kevin; Nkrumah, Francis; Ritchie, Thomas L; Franke, Eileen D; Binka, Fred N; Horton, John; Hoffman, Stephen L

    2003-03-01

    Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, double-blind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%-43%); for 50 mg/week, 84% (95% CI, 75%-91%); for 100 mg/week, 87% (95% CI, 78%-93%); and for 200 mg/week, 86% (95% CI, 76%-92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%-93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population.

  8. Safety and Efficacy of MLC601 in Iranian Patients after Stroke: A Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    A. A. Harandi

    2011-01-01

    Full Text Available Objective. To investigate the safety and efficacy of MLC601 (NeuroAid as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 1 month ischemic stroke. All patients were given either MLC601 (100 patients or placebo (50 patients, 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P>.05. Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P<.001. Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases.

  9. 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.

  10. 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.

  11. A randomized, double-blind, placebo-controlled trial to determine the effects of topical insulin on wound healing.

    Science.gov (United States)

    Rezvani, Omid; Shabbak, Elahe; Aslani, Abolfazl; Bidar, Ramin; Jafari, Mehrdad; Safarnezhad, Saeed

    2009-08-01

    Although the literature contains evidence demonstrating the beneficial effects of insulin on wound healing, no suitable method for the routine administration of insulin has been reported. A randomized, double-blind, placebo-controlled trial was conducted to determine the safety and efficacy of topical insulin on healing in 45 patients (29 men, mean age for both groups 40.62 years, range 12 to 71 years) with noninfected acute and chronic extremity wounds. Patients were randomly assigned to twice-daily topical application (spray) of 1 cc saline 0.9% for each 10 cm2 of wound with or without 10 units (0.1 cc) of insulin crystal and insulin. The endpoint was complete wound closure. Systemic glucose levels were measured before and 1 hour after treatment application. No patients developed signs or symptoms of hypoglycemia and glucose levels pre- and post-application did not differ significantly. Time to healing did not differ significantly between treatment groups. Healing rates were affected by baseline wound area, patient age, wound type (acute versus chronic), and treatment group. The mean rate of healing rate was 46.09 mm2/day in the treatment and 32.24 mm2/day in the control group (P = 0.029), independent of baseline wound size. In this study, the topical application of insulin was safe and effective. Clinical studies with a larger sample size and that include patients with diabetes mellitus are warranted.

  12. 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.

  13. Effectiveness of Topical Sucralfate in the Management of Pressure Ulcer in Hospitalized Patients: A Prospective, Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Ala, Shahram; Saeedi, Majid; Gholipour, Afshin; Ahmadi, Motahareh; Asoodeh, Ali; Shiva, Afshin

    2018-04-10

    The aim of this study was to evaluate the effectiveness of topical sucralfate in the management of pressure ulcer (PU) in hospitalized patients. Forty hospitalized patients with stage II PU were included in this prospective, double-blind, randomized, placebo-controlled trial and were randomly divided into 2 groups receiving either sucralfate gel or placebo, on a daily basis. The patients were visited every day for 14 days, the ulcer was evaluated using the Pressure Ulcer Scale for Healing (PUSH) and changes to the measured scores over time were used as an indicator of wound healing. There were no statistically significant differences in any of the demographic characteristics between both groups. Both of the interventions reduced the average PUSH score, and at the end of the trial, all but 2 patients were healed. One in each group discontinued the trial because of exacerbation of the ulcer. No significant between-group difference in the average PUSH score reduction was observed (6.36 ± 2.11 vs. 5.89 ± 1.41, P = 0.42). Although the average healing time was less in the sucralfate group (6.05 ± 2.17 vs. 7.78 ± 3.42), the difference was not statistically significant (P = 0.07). Sucralfate gel does not improve healing of PU compared with placebo.

  14. Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Nottage, Michelle; McLachlan, Sue-Anne; Brittain, Mary-Anne; Oza, Amit; Hedley, David; Feld, Ronald; Siu, Lillian L; Pond, Gregory; Moore, Malcolm J

    2003-01-01

    A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of a sucralfate mouthwash in preventing and alleviating oral mucositis induced by 5-fluorouracil (5FU). A total of 81 patients with colorectal cancer were enrolled. Patients were studied during their first cycle of chemotherapy with 5FU and leucovorin (LV) daily for 5 days every 4 weeks (Mayo Clinic schedule). Patients were randomly allocated to receive either a sucralfate suspension or a placebo suspension that was identical in appearance. Patients were instructed to use the suspension as a mouthwash four times daily from the beginning of the chemotherapy cycle. All patients received oral cryotherapy. Patients graded the severity of their own symptoms on a daily basis, and this was the primary outcome measure. There was no difference in the frequency or severity of oral mucositis between the sucralfate- and the placebo-treated group. Some mucositis was reported by 79% of the patient group. Assessment of mucositis by trial staff underestimated the incidence of this problem. Results of this trial do not support the hypothesis that a sucralfate mouthwash can prevent or alleviate oral mucositis induced by 5FU. Patient reporting of mucositis is a more sensitive instrument for assessment of mucositis than review by medical staff.

  15. A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage.

    Science.gov (United States)

    Misra, U K; Kalita, J; Pandey, S; Mandal, S K; Srivastava, M

    2005-12-15

    Due of paucity of studies on stress ulcer prophylaxis in intracerebral hemorrhage (ICH), we have evaluated the usefulness of ranitidine and sucralfate in preventing gastric hemorrhage (GH) in patients with ICH. In a hospital-based randomized placebo-controlled study, patients with CT-proven ICH within 7 days of ictus were randomized into ranitidine 50 mg i.v. eight hourly, sucralfate 1 g six hourly and placebo groups. Patients were conservatively managed. Primary endpoint was occurrence of GH within 15 days of ictus and secondary endpoint 1-month mortality. The mean age of the patients was 57.2 (range 25-90) years and 40 were females. There were 45 patients in ranitidine, 49 in sucralfate and 47 in placebo group. Demographic, clinical and radiological features were not significantly different in 3 groups. GH occurred in 11 (23.4%) patients in placebo, 5 (11.1%) in ranitidine and 7 (14.3%) in sucralfate group, which was not significant. Only one female had GH. There were 13 (27.7%) deaths in placebo, 5 (11.1%) in ranitidine and 12 (24.5%) in sucralfate group. Pneumonia occurred in placebo group in 5 (10.6%), ranitidine in 2 (4.4%) and sucralfate in 5 (10.2%) patients, which was not significantly different. Ranitidine and sucralfate do not seem to significantly prevent GH or reduce 1-month mortality.

  16. Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Foroogh Namjoyan

    2016-01-01

    Full Text Available The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001. The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood.

  17. 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.

  18. Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells.

    Science.gov (United States)

    Sawires, Happy; Botrous, Osama

    2012-07-01

    Breath-holding spells (BHS) are apparently frightening events occurring in otherwise healthy children.The aim of this study was to evaluate the efficacy of piracetam in the treatment of breath-holding spells. Forty patients with BHS (who were classified into two groups)were involved in a double-blinded placebo-controlled prospective study. Piracetam was given to group A while group B received placebo. Patients were followed monthly for a total period of 4 months. The numbers of attacks/month before and monthly after treatment were documented, and the overall number of attacks/month after treatment was calculated in both groups. The median number of attacks/month before treatment in the two groups was 5.5 and 5,respectively, while after the first month of treatment, it was 2 and 5, respectively. The median overall number of attacks/month after treatment in both groups was 1 and 5, respectively.There was a significant decline of number of attacks after piracetam treatment compared to placebo (p valuepiracetam throughout the study period. In conclusion, piracetam is a safe and effective drug for the treatment of breath-holding spells in children.

  19. 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.

  20. Antiobesity Effect of Caraway Extract on Overweight and Obese Women: A Randomized, Triple-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mahnaz Kazemipoor

    2013-01-01

    Full Text Available Caraway (Carum carvi L., a potent medicinal plant, is traditionally used for treating obesity. This study investigates the weight-lowering effects of caraway extract (CE on physically active, overweight and obese women through a randomized, triple-blind, placebo-controlled clinical trial. Seventy overweight and obese, healthy, aerobic-trained, adult females were randomly assigned to two groups (n=35 per group. Participants received either 30 mL/day of CE or placebo without changing their diet or physical activity. Subjects were examined at baseline and after 90 days for changes in body composition, anthropometric indices, and clinical and paraclinical variables. The treatment group, compared with placebo, showed a significant reduction of weight, body mass index, body fat percentage, and waist-to-hip ratio. No changes were observed in lipid profile, urine-specific gravity, and blood pressure of subjects. The results suggest that a dietary CE with no restriction in food intake, when combined with exercise, is of value in the management of obesity in women wishing to lower their weight, BMI, body fat percentage, and body size, with no clinical side effects. In conclusion, results of this study suggest a possible phytotherapeutic approach for caraway extract in the management of obesity. This trial is registered with NCT01833377.

  1. Randomised placebo-controlled trials and HIV-infected pregnant women in developing countries. Ethical imperialism or unethical exploitation?

    Science.gov (United States)

    de Zulueta, P

    2001-08-01

    The maternal-fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki--the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against the controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow 'local conditions' to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta-ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects.

  2. 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.

  3. 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.

  4. Erdosteine reduces the exercise-induced oxidative stress in patients with severe COPD: Results of a placebo-controlled trial.

    Science.gov (United States)

    Dal Negro, Roberto W; Visconti, Maria

    2016-12-01

    Erdosteine (ER), a multimechanism, mucoactive agent with anti-oxidant and anti-inflammatory properties, has been shown to improve lung function, decrease plasma reactive oxygen species (ROS), and 8-isoprostane levels in patients with chronic obstructive pulmonary disease (COPD). To assess vs. placebo the effect of ER on the exercise-induced oxidative stress by measuring and comparing the release of pro-inflammatory mediators in severe COPD patients. The double blind, placebo controlled study was carried out in 24 severe (GOLD Class III) COPD patients, aged >40 yr, randomized to receive either oral ER (600 mg/day, 8 males, mean age 70.5 yr) or placebo (9 males, mean age 70.8 yr) for 10 days. All patients performed a 6-min walking test (6MWT) before and after both treatments. Mean ROS plasma levels increased significantly, but equally, in each group following the baseline 6MWT (p = ns). At the end of both treatments, a significant difference in mean plasma ROS increase from baseline became clear between the ER (+14.6% ± 2.7) and the placebo group (+24.4% ± 3.8) after the second 6MWT (p release of inflammatory mediators due to the exercise-induced oxidative stress in severe COPD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Clinical effect of intratympanic dexamethasone injection in acute unilateral tinnitus: A prospective, placebo-controlled, multicenter study.

    Science.gov (United States)

    Lee, Hyun-Jin; Kim, Min-Beom; Yoo, Shin-Young; Park, Shi Nae; Nam, Eui-Cheol; Moon, In Seok; Lee, Ho-Ki

    2018-01-01

    The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection (ITDI) in acute tinnitus of presumed cochlear origin. A prospective, randomized, placebo-controlled, double-blinded, multicenter study. Between August 2013 and December 2015, 54 patients with unilateral tinnitus were enrolled at four different centers. Patients were assigned either to an ITDI (n = 27) or an intratympanic normal saline injection (ITNI; n = 27) group through block randomization. Intratympanic injections were administered four times over 2 weeks. At 4 weeks after initial injection, we analyzed the improvement rates of tinnitus using the tinnitus handicap Inventory (THI) and visual analogue scale (VAS) for loudness, awareness, and annoyance. We defined improvement as the reduction of more than 7 points or of more than 20% in the final THI score compared to the initial THI score. The initial mean hearing thresholds and VAS and THI scores of the two groups did not differ significantly. At 4 weeks after initial injection, the mean VAS and THI scores of both groups had significantly reduced. However, the improvement rate did not differ significantly between the groups (ITDI, 51.9%; ITNI, 59.3%). The results indicate that ITDI might not be more effective than ITNI for the treatment of acute unilateral tinnitus. Therefore, ITDI should not be considered as the main treatment for patients presenting with acute tinnitus as the primary symptom. 1b. Laryngoscope, 128:184-188, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  6. A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy.

    Science.gov (United States)

    Goemans, Nathalie; Mercuri, Eugenio; Belousova, Elena; Komaki, Hirofumi; Dubrovsky, Alberto; McDonald, Craig M; Kraus, John E; Lourbakos, Afrodite; Lin, Zhengning; Campion, Giles; Wang, Susanne X; Campbell, Craig

    2018-01-01

    This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and 10-meter walk/run velocity) gave consistent findings. Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity. The increased standard deviation alone, due to less stringent inclusion/exclusion criteria, reduced the statistical power from pre-specified 90% to actual 53%. Therefore, a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300-400 meters and ability to rise from floor. A statistically significant improvement in 6MWD of 35.4 meters (P = 0.039) in favor of drisapersen was observed in this subpopulation. Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Oral misoprostol with mifepristone versus misoprostol alone for inducing labor in intrauterine fetal death: A randomized placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Yazhini Arjunan

    2017-01-01

    Full Text Available Context: Intrauterine fetal death (IUFD causes emotional distress and could result in intrauterine infection. In view of these complications, medical induction is recommended, if it is safe. Aim: The aim of this study was to compare the efficacy and safety of a combination of mifepristone and misoprostol with oral misoprostol alone for induction of labor in IUFD. Settings and Design: This is a randomized placebo-controlled trial conducted at a tertiary care teaching hospital in southern India. Patients and Methods: We recruited 72 women with IUFD in a singleton pregnancy after 28 weeks with intact membranes. Thirty-six women received oral placebo followed by misoprostol. In other group, 36 women received 200 mg oral mifepristone followed by misoprostol (both groups received 50 μg orally 4th hourly up to 5 doses. The interval between mifepristone/placebo and the first dose of misoprostol was 24 h. Results: Successful delivery occurred within 72 h in 31 of 36 (86% women who received mifepristone before misoprostol and in 28 of 36 (78% women who received only misoprostol (P = 0.541. Median (interquartile range induction to delivery interval was 3.5 (2–5 and 4 (3–5 h in the combination group and misoprostol group, respectively (P = 0.465. Conclusions: Addition of mifepristone to misoprostol appears to be marginally more effective than misoprostol alone for induction of labor in intermediate and late IUFD, although the differences were not statistically significant.

  8. 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).

  9. Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Necek Magdalena

    2008-05-01

    Full Text Available Abstract Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713

  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. Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Modabbernia, Amirhossein; Ashrafi, Mandana; Hassanzadeh, Elmira; Forghani, Saeedeh; Akhondzadeh, Shahin

    2013-01-01

    Autism is associated with activation of the inflammatory response system. This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autism In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C. Significant time × treatment interaction was observed for Irritability (F (1.658, 63.021) = 13.580, P autism. (Registration, www.irct.ir ; IRCT138711091556N2).

  13. Vitamin C as an adjuvant for treating major depressive disorder and suicidal behavior, a randomized placebo-controlled clinical trial.

    Science.gov (United States)

    Sahraian, Ali; Ghanizadeh, Ahmad; Kazemeini, Fereshteh

    2015-03-14

    There are some animal studies suggesting the possible role of vitamin C for treating depression. However, the efficacy of vitamin C for treating adult patients with major depressive disorder (MDD) has never been examined. This 8-week randomized double-blind placebo-controlled clinical trial included adult patients with major depressive disorder according to DSM-IV diagnostic criteria. Twenty-one patients in the treatment group received citalopram plus vitamin C and the 22 patients in the control group received citalopram plus placebo. The Hamilton Depression Rating Scale was used to measure depressive symptoms at baseline, week 2, week 4, and week 8. We also checked for the presence of adverse effects. While depression symptoms decreased in both groups during this trial, there was no statistically significant difference between the 2 groups (P = .5). The rate of remission, partial response, and complete response was not different between the two groups. The rate of adverse effects were not different between the two groups. Adding vitamin C to citalopram did not increase the efficacy of citalopram in MDD patients. Vitamin C plus citalopram is as effective as placebo plus citalopram for treating adult patients with suicidal behavior. No serious adverse effect for this combination was identified during this trial. This trial was registered at http://www.irct.ir . The registration number of this trial was: IRCT201312263930N31 . Date registered: 5 July 2014.

  14. Varenicline for opioid withdrawal in patients with chronic pain: a randomized, single-blinded, placebo controlled pilot trial.

    Science.gov (United States)

    Hooten, W Michael; Warner, David O

    2015-03-01

    The objectives of this randomized, single-blinded, placebo-controlled pilot trial were to investigate the effects of varenicline on opioid withdrawal among chronic pain patients undergoing opioid detoxification in an interdisciplinary pain program and the feasibility of varenicline use in this population. Twenty-one patients were recruited (varenicline=10, placebo=11), and 7 patients in the varenicline and 11 in the placebo group completed the study. Opioid withdrawal was quantified using the Clinical Opiate Withdrawal Scale, and varenicline-related adverse effects were assessed. Opioid withdrawal scores tended to decrease over the course of opioid tapering in those receiving varenicline and increase in those receiving placebo. Varenicline was well-tolerated in this population, with no adverse drug effects (including nausea) observed and no effect on improvements in pain severity and depression. This randomized pilot study provides preliminary data for future trials of varenicline in opioid-dependent adults with chronic pain undergoing medically directed opioid detoxification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. A randomized placebo-controlled trial of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

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

    2013-08-01

    A double-blind, randomized, placebo-controlled study was designed to assess the efficacy and safety of electroencephalographic (EEG) neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD). The study started in August 2008 and ended in July 2012 and was conducted at Karakter Child and Adolescent Psychiatry University Centre in Nijmegen, The Netherlands. Forty-one children (aged 8-15 years) with a DSM-IV-TR diagnosis of ADHD were randomly assigned to treatment with either EEG neurofeedback (n = 22) or placebo neurofeedback (n = 19) for 30 sessions, given as 2 sessions per week. The children were stratified by age, electrophysiologic state of arousal, and medication use. Everyone involved in the study, except the neurofeedback therapist and the principal investigator, was blinded to treatment assignment. The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV, scored at baseline, during treatment, and at study end. Clinical improvement as measured by the Clinical Global Impressions-Improvement scale (CGI-I) was a secondary outcome. While total ADHD symptoms improved over time in both groups (F1,39 = 26.56, P neurofeedback was not superior to placebo neurofeedback in improving ADHD symptoms in children with ADHD. ClinicalTrials.gov identifier: NCT00723684. © Copyright 2013 Physicians Postgraduate Press, Inc.

  16. 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.

  17. Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Weintraub, Michael I; Wolfe, Gil I; Barohn, Richard A; Cole, Steven P; Parry, Gareth J; Hayat, Ghazala; Cohen, Jeffrey A; Page, Jeffrey C; Bromberg, Mark B; Schwartz, Sherwyn L

    2003-05-01

    To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN). Randomized, placebo-control, parallel study. Forty-eight centers in 27 states. Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device. Nerve conduction and/or quantified sensory testing were performed serially. Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (ANCOVA), and chi-square analysis were performed. There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, -12%; for sham, -3%; P<.05, ANCOVA), numbness and tingling (magnet, -10%; sham, +1%; P<.05, ANCOVA), and exercise-induced foot pain (magnet, -12%; sham, -4%; P<.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, -32%; sham, -14%; P<.01, ANOVA) and foot pain (magnet, -41%; sham, -21%; P<.01, ANOVA). Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.

  18. N-acetyl cysteine for depressive symptoms in bipolar disorder--a double-blind randomized placebo-controlled trial.

    Science.gov (United States)

    Berk, Michael; Copolov, David L; Dean, Olivia; Lu, Kristy; Jeavons, Sue; Schapkaitz, Ian; Anderson-Hunt, Murray; Bush, Ashley I

    2008-09-15

    Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorder are complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder. A randomized, double-blind, multicenter, placebo-controlled study of individuals (n = 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning. NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: -8.05 [-13.16, -2.95], p = .002) and most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p = .968) and no significant between-group differences in adverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts. NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder.

  19. A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state.

    Directory of Open Access Journals (Sweden)

    Ashwin Patkar

    Full Text Available OBJECTIVE: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD. METHODS: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE, while also meeting 2 or 3 (but not more nor less DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. RESULTS: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038. Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036. Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. CONCLUSIONS: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. TRIAL REGISTRATION: Clinicaltrials.gov NCT00490542.

  20. 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.

  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. Safety of ingestion of yellow tartrazine by double-blind placebo controlled challenge in 26 atopic adults.

    Science.gov (United States)

    Pestana, S; Moreira, M; Olej, B

    2010-01-01

    Yellow dye tartrazine is a potential cause of exacerbations of asthma, allergic rhinitis and urticaria in atopic patients. The Brazilian Sanitary Surveillance Agency (ANVISA) published a consultation about the possibility of issuing a label warning addressing these potential effects of food and drugs containing tartrazine. The present study aims to evaluate tartrazine dye safety in atopic subjects suffering from allergic rhinitis, asthma, urticaria or sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). Atopic patients with allergic rhinitis, asthma, urticaria or pseudo-allergic reactions to non-steroidal anti-inflammatory drugs were studied (n=26). The gold standard, double-blind placebo controlled, crossed-over challenge was used There were no statistical differences between placebo and drug in cutaneous, respiratory or cardiovascular aspects. In a group of atopic subjects with allergic rhinitis, asthma, urticaria or pseudo-allergic reactions to non-steroidal anti-inflammatory drugs, the administration of 35 mg of the tartrazine dye did not precipitate any kind of significant cutaneous, respiratory or cardiovascular reactions when compared to placebo. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  3. 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.

  4. The safety, effectiveness and cost-effectiveness of cytisine in achieving six-month continuous smoking abstinence in tuberculosis patients - protocol for a double-blind, placebo-controlled randomised trial.

    Science.gov (United States)

    Dogar, Omara; Barua, Deepa; Boeckmann, Melanie; Elsey, Helen; Fatima, Razia; Gabe, Rhian; Huque, Rumana; Keding, Ada; Khan, Amina; Kotz, Daniel; Kralikova, Eva; Newell, James N; Nohavova, Iveta; Parrott, Steve; Readshaw, Anne; Renwick, Lottie; Sheikh, Aziz; Siddiqi, Kamran

    2018-04-20

    Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. Behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit, in general populations. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost-effectiveness of cytisine - a low-cost plant-derived nicotine substitute - for smoking cessation in TB patients compared with placebo, over and above brief behavioural support. Two-arm, parallel, double-blind, placebo-controlled, multi-centre (30 sites in Bangladesh and Pakistan), individually randomised trial. TB treatment centres integrated into public health care systems in Bangladesh and Pakistan. Newly diagnosed (in the last four weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n= 2,388). The primary outcome measure is biochemically verified continuous abstinence from smoking at six months post-randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events. This is the first smoking cessation trial of cytisine in low- and middle-income countries evaluating both cessation and tuberculosis (TB) outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke. This article is protected by copyright. All rights reserved.

  5. Effect of vitamin D, calcium and multiple micronutrient supplementation on vitamin D and bone status in Bangladeshi premenopausal garment factory workers with hypovitaminosis D: a double-blinded, randomised, placebo-controlled 1-year intervention.

    Science.gov (United States)

    Islam, Md Zahirul; Shamim, Abu Ahmed; Viljakainen, Heli T; Akhtaruzzaman, Mohammad; Jehan, Atia H; Khan, Habib Ullah; Al-Arif, Ferdaus Ahmad; Lamberg-Allardt, Christel

    2010-07-01

    Due to little outdoor activity and low dietary intake of vitamin D (VD), Bangladeshi low-income women are at risk for osteoporosis at an early age. The present study assessed the effect of VD, Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers. This placebo-controlled 1-year intervention randomly assigned 200 apparently healthy subjects (aged 16-36 years) to four groups: VD group, daily 10 microg VD; VD and Ca (VD-Ca) group, daily 10 microg VD+600 mg Ca; multiple micronutrient and Ca (MMN-Ca) group, 10 microg VD and other micronutrients+600 mg Ca; a placebo group. Serum 25-hydroxyvitamin D (S-25OHD), intact parathyroid hormone (S-iPTH), Ca, phosphate and alkaline phosphatase were measured. Bone mineral density and bone mineral content were measured by dual-energy X-ray absorptiometry. All measurements were made at baseline and at 12 months. Significantly (P S-25OHD concentrations were observed in the supplemented groups than in the placebo group after the intervention. Supplementation had an effect (P S-iPTH in the VD-Ca and MMN-Ca groups compared with the placebo group. Bone mineral augmentation increased at the femur in the supplemented groups. Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects. MMN-Ca may have analogous positive health implications with additional non-skeletal benefits.

  6. A Multicenter, Randomized, Open-Labeled, Parallel Group Trial of Sildenafil in Alcohol-Associated Erectile Dysfunction: The Impact on Psychosocial Outcomes

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    Alexander Grinshpoon

    2009-09-01

    Full Text Available To examine the effect of sildenafil on erectile dysfunction (ED and psychosocial outcomes in alcohol-dependent (AD men, 108 men with these diagnoses were randomly assigned to either take sildenafil (50 mg as add-on to standard treatment for AD, or the same treatment without sildenafil, for 12 weeks. Only 50 patients in sildenafil group and 51 in control group twice completed the International Index of Erectile Function (IIEF and a battery of self-report questionnaires. IIEF scores and psychosocial functioning, self-esteem and support from friends improved only for sildenafil-treated patients (P < 0.001. The high effect sizes suggest that the observed benefits are unlikely to be a placebo effect, although their unspecific nature could not be ruled out. In men with ED associated with AD, sildenafil improves both ED and psychosocial outcomes. Further placebo-controlled clinical trial is warranted.

  7. Tocolysis for repeat external cephalic version in breech presentation at term: a randomised, double-blinded, placebo-controlled trial.

    Science.gov (United States)

    Impey, Lawrence; Pandit, Meghana

    2005-05-01

    External cephalic version (ECV) reduces the incidence of breech presentation at term and caesarean section for non-cephalic births. Tocolytics may improve success rates, but are time consuming, may cause side effects and have not been proven to alter caesarean section rates. The aim of this trial was to determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. To determine whether tocolysis should be used if ECV is being re-attempted after a failed attempt. Randomised, double-blinded, placebo-controlled trial. UK teaching hospital. One hundred and twenty-four women with a breech presentation at term who had undergone an unsuccessful attempt at ECV. Relative risks with 95% confidence intervals for categorical variables and a t test for continuous variables. Analysis was by intention to treat. Incidence of cephalic presentation at delivery. Secondary outcomes were caesarean section and measures of neonatal and maternal morbidity. The use of tocolysis for a repeat attempt at ECV significantly increases the incidence of cephalic presentation at delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62). Maternal and neonatal morbidity remain unchanged. The use of tocolysis increases the success rate of repeat ECV and reduces the incidence of caesarean section. A policy of only using tocolysis where an initial attempt has failed leads to a relatively high success rate with minimum usage of tocolysis.

  8. Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

    Science.gov (United States)

    Wali, Ramesh K; Bianchi, Laura; Kupfer, Sonia; De La Cruz, Mart; Jovanovic, Borko; Weber, Christopher; Goldberg, Michael J; Rodriguez, L M; Bergan, Raymond; Rubin, David; Tull, Mary Beth; Richmond, Ellen; Parker, Beth; Khan, Seema; Roy, Hemant K

    2018-01-01

    Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. ClinicalTrials.gov NCT00828984.

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

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    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.

  10. The Efficacy of Vitamin C on Postoperative Outcomes after Posterior Lumbar Interbody Fusion: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Lee, Gun Woo; Yang, Han Seok; Yeom, Jin S; Ahn, Myun-Whan

    2017-09-01

    Vitamin C has critical features relavant to postoperative pain management and functional improvement; however, no study has yet evaluated the effectiveness of vitamin C on improving the surgical outcomes for spine pathologies. Thus, this study aimed to explore the impact of vitamin C on postoperative outcomes after single-level posterior lumbar interbody fusion (PLIF) for lumbar spinal stenosis in prospectively randomized design. We conducted a 1-year prospective, randomized, placebo-controlled, double-blind study to evaluate the impact of vitamin C on the postoperative outcomes after PLIF surgery. A total of 123 eligible patients were randomly assigned to either group A (62 patients with vitamin C) or group B (61 patients with placebo). Patient follow-up was continued for at least 1 year after surgery. The primary outcome measure was pain intensity in the lower back using a visual analogue scale. The secondary outcome measures were: (1) the clinical outcome assessed using the Oswestry Disability Index (ODI); (2) the fusion rate assessed using dynamic radiographs and computed tomography scans; and (3) complications. Pain intensity in the lower back was significantly improved in both groups compared with preoperative pain intensity, but no significant difference was observed between the 2 groups over the follow-up period. The ODI score of group A at the third postoperative month was significantly higher than the score of group B. After the sixth postoperative month, the ODI score of group A was slightly higher than the score of group B; however, this difference was not significant. The fusion rates at 1 year after surgery and the complication rates were not significantly different between the 2 groups. Postoperative pain intensity, the primary outcome measure, was not significantly different at 1 year after surgery between the 2 groups. However, vitamin C may be associated with improving functional status after PLIF surgery, especially during the first 3

  11. Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Irani, Mohamad; Seifer, David B; Grazi, Richard V; Julka, Nitasha; Bhatt, Devika; Kalgi, Bharati; Irani, Sara; Tal, Oded; Lambert-Messerlian, Geralyn; Tal, Reshef

    2015-11-01

    There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis. The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. This was a prospective, randomized, placebo-controlled trial. The study was conducted at an academic-affiliated medical center. Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks. Serum TGF-β1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment. The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P PCOS significantly decreases the bioavailability of TGF-β1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-β drugs.

  12. Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial.

    Science.gov (United States)

    Lieverse, Ritsaert; Van Someren, Eus J W; Nielen, Marjan M A; Uitdehaag, Bernard M J; Smit, Jan H; Hoogendijk, Witte J G

    2011-01-01

    Major depressive disorder (MDD) in elderly individuals is prevalent and debilitating. It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus, the biological clock of the brain. Circadian rhythm disturbances are common in the elderly. Suprachiasmatic nucleus stimulation using bright light treatment (BLT) may, therefore, improve mood, sleep, and hormonal rhythms in elderly patients with MDD. To determine the efficacy of BLT in elderly patients with MDD. Double-blind, placebo-controlled randomized clinical trial. Home-based treatment in patients recruited from outpatient clinics and from case-finding using general practitioners' offices in the Amsterdam region. Eighty-nine outpatients 60 years or older who had MDD underwent assessment at baseline (T0), after 3 weeks of treatment (T1), and 3 weeks after the end of treatment (T2). Intervention Three weeks of 1-hour early-morning BLT (pale blue, approximately 7500 lux) vs placebo (dim red light, approximately 50 lux). Mean improvement in Hamilton Scale for Depression scores at T1 and T2 using parameters of sleep and cortisol and melatonin levels. Intention-to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT more than placebo from T0 to T1 (7%; 95% confidence interval, 4%-23%; P = .03) and from T0 to T2 (21%; 7%-31%; P = .001). At T1 relative to T0, get-up time after final awakening in the BLT group advanced by 7% (P hour urinary free cortisol level was 37% lower (P = .003) compared with the placebo group. The evening salivary cortisol level had decreased by 34% in the BLT group compared with an increase of 7% in the placebo group (P = .02). In elderly patients with MDD, BLT improved mood, enhanced sleep efficiency, and increased the upslope melatonin level gradient. In addition, BLT produced continuing improvement in mood and an attenuation of cortisol hyperexcretion after discontinuation of treatment. clinicaltrials

  13. Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

    Science.gov (United States)

    Tarumi, Yoko; Wilson, Mitchell P; Szafran, Olga; Spooner, G Richard

    2013-01-01

    The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. To assess the efficacy of docusate in hospice patients. This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  14. Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial.

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    A James Daveson

    Full Text Available BACKGROUND AND AIMS: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten. METHODS: In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge. RESULTS: Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes. CONCLUSIONS: Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology. TRIAL REGISTRATION: ClinicalTrials.gov NCT00671138.

  15. Efficacy of N-Acetylcysteine Augmentation on Obsessive Compulsive Disorder: A Multicenter Randomized Double Blind Placebo Controlled Clinical Trial

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    Ahmad Ghanizadeh

    2017-04-01

    Full Text Available Objective: Glutamate is considered a target for treating obsessive-compulsive disorder (OCD. The efficacy and safety of the nutritional supplement of N-Acetylcysteine (NAC as an adjuvant to serotonin reuptake inhibitor (SSRI for treating children and adolescents with OCD has never been examined.Methods: This was a 10-week randomized double-blind placebo-controlled clinical trial with 34 OCD outpatients. The patients received citalopram plus NAC or placebo. Yale-Brown Obsessive-Compulsive Scale (YBOCS and Pediatric Quality of Life Inventory (PedsQL™ were used. Adverse effects were monitored.Results: YBOCS score was not different between the two groups at baseline, but the score was different between the two groups at the end of this trial (P<0.02. The YBOCS score of NAC group significantly decreased from 21.0(8.2 to 11.3(5.7 during this study. However, no statistically significant decrease of YBOCS was found in the placebo group. The Cohen’s d effect size was 0.83.The mean change of score of resistance/control to obsessions in the NAC and placebo groups was 1.8(2.3 and 0.8(2.1, respectively (P = 0.2. However, the mean score of change for resistance/control to compulsion in the NAC and placebo groups was 2.3(1.8 and 0.9(2.3, respectively. Cohen’s d effect size was 0.42.The score of three domains of quality of life significantly decreased in N-Acetylcysteine group during this trial. However, no statistically significant decrease was detected in the placebo group. No serious adverse effect was found in the two groups.Conclusion: This trial suggests that NAC adds to the effect of citalopram in improving resistance/control to compulsions in OCD children and adolescents. In addition, it is well tolerated.

  16. Visual improvements in vaginal mucosa correlate with symptoms of VVA: data from a double-blind, placebo-controlled trial.

    Science.gov (United States)

    Simon, James A; Archer, David F; Kagan, Risa; Bernick, Brian; Graham, Shelli; Constantine, Ginger D; Mirkin, Sebastian

    2017-09-01

    To evaluate the response of the vaginal mucosa with TX-004HR and its correlation with vulvar and vaginal atrophy (VVA) symptoms, and whether visual examination is a useful measure for assessing VVA. REJOICE was a 12-week, phase 3, multicenter, randomized, double-blind, placebo-controlled study of a vaginal, muco-adhesive, 17β-estradiol softgel capsule (TX-004HR 4, 10, and 25 μg) in postmenopausal women with VVA and moderate-to-severe dyspareunia. Treatments were self-administered vaginally once per day for 2 weeks, then twice per week for 10 weeks. The vagina was visually examined at baseline and at weeks 2, 6, 8, and 12; changes were evaluated using a 4-item scale for vaginal color, vaginal epithelial integrity, vaginal epithelial surface thickness, and vaginal secretions. Significant improvements were observed with all three TX-004HR doses versus placebo in vaginal color (least square mean score changes of -0.96 to -1.06 for TX-004HR doses vs -0.60 for placebo at week 12), epithelial integrity (-0.97 to -1.07 vs -0.60), epithelial surface thickness (-0.94 to -1.03 vs -0.61), and secretions (-1.01 to -1.06 vs -0.64) (P vaginal dryness (P vaginal mucosa of postmenopausal women with VVA and moderate-to-severe dyspareunia were observed with TX-004HR versus placebo, and vaginal mucosa assessment scores correlated with vaginal symptoms of dyspareunia and dryness. Visual vaginal assessment by healthcare professionals is a useful measure for diagnosing VVA and assessing response to treatment.

  17. 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

  18. Randomized, double-blinded, placebo-controlled trial comparing two multimodal opioid-minimizing pain management regimens following transsphenoidal surgery.

    Science.gov (United States)

    Shepherd, Deborah M; Jahnke, Heidi; White, William L; Little, Andrew S

    2018-02-01

    OBJECTIVE Pain control is an important clinical consideration and quality-of-care metric. No studies have examined postoperative pain control following transsphenoidal surgery for pituitary lesions. The study goals were to 1) report postoperative pain scores following transsphenoidal surgery, 2) determine if multimodal opioid-minimizing pain regimens yielded satisfactory postoperative pain control, and 3) determine if intravenous (IV) ibuprofen improved postoperative pain scores and reduced opioid use compared with placebo. METHODS This study was a single-center, randomized, double-blinded, placebo-controlled intervention trial involving adult patients with planned transsphenoidal surgery for pituitary tumors randomized into 2 groups. Group 1 patients were treated with scheduled IV ibuprofen, scheduled oral acetaminophen, and rescue opioids. Group 2 patients were treated with IV placebo, scheduled oral acetaminophen, and rescue opioids. The primary end point was patient pain scores (visual analog scale [VAS], rated 0-10) for 48 hours after surgery. The secondary end point was opioid use as estimated by oral morphine equivalents (OMEs). RESULTS Of 136 patients screened, 62 were enrolled (28 in Group 1, 34 in Group 2). The study was terminated early because the primary and secondary end points were reached. Baseline characteristics between groups were well matched except for age (Group 1, 59.3 ± 14.4 years; Group 2, 49.8 ± 16.2 years; p = 0.02). Mean VAS pain scores were significantly different, with a 43% reduction in Group 1 (1.7 ± 2.2) compared with Group 2 (3.0 ± 2.8; p transsphenoidal surgery. IV ibuprofen resulted in significantly improved pain scores and significantly decreased opioid use compared with placebo. Postoperative multimodal pain management, including a nonsteroidal antiinflammatory medication, should be considered after surgery to improve patient comfort and to limit opioid use. Clinical trial registration no.: NCT02351700 (clinicaltrials

  19. A natural seaweed derived mineral supplement (Aquamin F for knee osteoarthritis: A randomised, placebo controlled pilot study

    Directory of Open Access Journals (Sweden)

    Kuskowski Michael A

    2009-02-01

    Full Text Available Abstract Background Osteoarthritis (OA is a slowly destructive process that may be influenced by a nutritional mineral balance in the body. Methods This small, double blind, placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin on 6 minute walking distance (6 MWD, range of motion (ROM, and pain and joint mobility measured by the Western Ontario and McMaster Universities (WOMAC Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs (NSAIDs that were being used daily for pain management. Subjects (n = 29 with moderate to severe OA of the knee were randomised to receive either Aquamin (2400 mg/d or Placebo for up to 12 weeks. Results Of the 29 subjects initially randomized, only 22 subjects proceeded to treatment due to 7 subjects not meeting study selection criteria at baseline. Fourteen subjects completed the study and an ITT analysis (n = 22 of the data showed no significant differences in WOMAC scores however, the data did reveal significant improvements in passive and active extension ROM (0.83° ± 1.54 vs. -1.54° ± 2.43; difference, 5.2° ± 2.2, p = 0.028 and 6 MWD (150 ± 48 ft vs. 12.5 ± 31.5 ft; difference, 136 ± 57 ft, p = 0.03 in the Aquamin group compared to the placebo group; respectively, following a 50% reduction in NSAID use. The treatments were well tolerated and the adverse event profiles were not significantly different between the groups. Conclusion This small preliminary study suggests Aquamin may increase range of motion and walking distances in subjects with OA of the knee and may allow partial withdrawal of NSAIDs over 12 weeks of treatment. Additional research is needed to confirm these preliminary observations. Trial registration NCT00755482

  20. Effects of D-cycloserine on extinction of mesolimbic cue reactivity in alcoholism: a randomized placebo-controlled trial.

    Science.gov (United States)

    Kiefer, Falk; Kirsch, Martina; Bach, Patrick; Hoffmann, Sabine; Reinhard, Iris; Jorde, Anne; von der Goltz, Christoph; Spanagel, Rainer; Mann, Karl; Loeber, Sabine; Vollstädt-Klein, Sabine

    2015-07-01

    Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by cue-exposure-based extinction training (CET). Evidence from preclinical studies suggests that the extinction of conditioned alcohol-seeking behavior might be facilitated by drugs increasing N-methyl-D-aspartate (NMDA) receptor-associated memory consolidation. In this study, we assessed the efficacy of CET treatment supplemented with the partial NMDA-receptor agonist D-cycloserine (DCS) at reducing mesolimbic cue reactivity (CR), craving, and relapse risk in alcoholism. In a randomized, placebo-controlled, double-blind study, we recruited 76 recently detoxified abstinent alcohol-dependent patients. Thirty-two (16 DCS, 16 placebo) patients showed cue-induced ventral-striatal activation measured with functional magnetic resonance imaging (fMRI) prior to treatment and were thus included in the efficacy analyses. After inpatient detoxification, patients underwent nine sessions of CET spaced over 3 weeks, receiving either 50 mg DCS or placebo 1 h prior to each CET session. FMRI was conducted before treatment and 3 weeks after treatment onset. Following treatment with CET plus DCS, cue-induced brain activation in the ventral and dorsal striatum was decreased compared to treatment with CET plus placebo. Elevated posttreatment ventral striatal CR and increased craving (assessed using the Obsessive Compulsive Drinking Scale) were associated with increased relapse risk. DCS was shown to augment the effect of CET for alcohol-dependent subjects. The interaction between craving and ventral-striatal CR on treatment outcome suggests that CET might be especially effective in patients exhibiting both high craving and elevated CR.

  1. Treatment of comorbid migraine and temporomandibular disorders: a factorial, double-blind, randomized, placebo-controlled study.

    Science.gov (United States)

    Goncalves, Daniela A G; Camparis, Cinara M; Speciali, José G; Castanharo, Sabrina M; Ujikawa, Liliana T; Lipton, Richard B; Bigal, Marcelo E

    2013-01-01

    To investigate the effectiveness of single and concomitant treatment of migraine and temporomandibular disorders (TMD) in women with the comorbidity. Eligible female patients met International Classification of Headache Disorders, second edition (ICHD-2) criteria for migraine with or without aura and the Research Diagnostic Criteria for myofascial TMD (Grade ll or lll). After a run-in period (30 days), women with both migraine and TMD were enrolled into a four-arm, double-blind, placebo-controlled, factorial study testing the separate and joint effects of a migraine treatment (propranolol 90 mg) and a TMD treatment (stabilization splint [SS]) in four groups of patients. The four treatment groups were propranolol and SS (n = 22); propranolol placebo and SS (n = 23); propranolol and non-occlusal splint (NOS) (n = 23); and propranolol placebo and NOS (n = 21). The primary endpoint for migraine was change in headache days from baseline to the third month, and the secondary endpoint was change in days with at least moderate headache in the same period. The TMD endpoints included pain threshold and mandibular vertical range of motion. Data were analyzed using analysis of variance (ANOVA, Dunn's post-hoc test) or Kruskal-Wallis test. For the primary endpoint, in intention-to-treat (ITT) analyses (n = 94), propranolol and SS were associated with a nonsignificant reduction in the number of headache days, relative to all other groups. For per-protocol (PP) Completer analyses (n = 89), differences in the number of headache days reached significance (P headache endpoints and in disability, in both ITT and PP analyses. No significant differences among groups were seen for the TMD parameters. In women with TMD and migraine, migraine significantly improved only when both conditions were treated. The best treatment choice for TMD pain in women with migraine is yet to be defined.

  2. A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

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    Ajit Rayamajhi

    Full Text Available Japanese encephalitis (JE virus (JEV is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial.We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group died during treatment and two (placebo subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2, which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.ClinicalTrials.gov NCT01856205.

  3. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

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    Biesiekierski, Jessica R; Newnham, Evan D; Irving, Peter M; Barrett, Jacqueline S; Haines, Melissa; Doecke, James D; Shepherd, Susan J; Muir, Jane G; Gibson, Peter R

    2011-03-01

    Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

  4. Evaluation of homoeopathic treatment in polycystic ovary syndrome: A single-blind, randomised, placebo-controlled pilot study

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    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.

  5. Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

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    Yousefichaijan, Parsa; Cyrus, Ali; Dorreh, Fatemeh; Rafeie, Mohammad; Sharafkhah, Mojtaba; Frohar, Faryar; Safi, Fatemeh

    2015-12-01

    Nephrolithiasis in children is associated with a high rate of complications and recurrence. Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P field.

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

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    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

  7. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial.

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    Morgan, Annette; Stevens, John

    2010-07-01

    The objective of this study was to investigate the effectiveness of Bacopa monnieri Linn. for improvement of memory performance in healthy older persons. This was a randomized, double-blind, placebo-controlled trial. The trial took place in Lismore, NSW, Australia between February and July 2005. Ninety-eight (98) healthy participants over 55 years of age were recruited from the general population. Participants were randomized to receive an extract of Bacopa monnieri called BacoMind(TM) (Natural Remedies Pvt. Ltd.), 300 mg/day, or an identical placebo. Following screening, neuropsychologic and subjective memory assessments were performed at baseline and at 12 weeks. Audioverbal and visual memory performance were measured by the Rey Auditory Verbal Learning Test (AVLT), the Rey-Osterrieth Complex Figure Test (CFT), and the Reitan Trail Making Test (TMT). Subjective memory performance was measured by the Memory Complaint Questionnaire (MAC-Q). One hundred and thirty-six (136) subjects volunteered; 103 met entry criteria, 98 commenced, and 81 completed the trial. Bacopa significantly improved verbal learning, memory acquisition, and delayed recall as measured by the AVLT: trial a4 (p = 0.000), trial a5 (p = 0.016); trial a6 (p = 0.000); trial a7 (delayed recall) (p = 0.001); total learning (p = 0.011); and retroactive interference (p = 0.048). CFT, MAC-Q, and TMT scores improved but group differences were not significant. Bacopa versus placebo caused gastrointestinal tract (GIT) side-effects. Bacopa significantly improved memory acquisition and retention in healthy older Australians. This concurs with previous findings and traditional use. Bacopa caused GIT side-effects of increased stool frequency, abdominal cramps, and nausea.

  8. Synbiotics could not reduce the scoring of childhood atopic dermatitis (SCORAD): a randomized double blind placebo-controlled trial.

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    Shafiei, Alireza; Moin, Mostafa; Pourpak, Zahra; Gharagozlou, Mohammad; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Sajedi, Vahid; soheili, Habib; Sotoodeh, Soheila; Movahedi, Masoud

    2011-03-01

    Despite preliminary evidence, the role of probiotic and synbiotic in treatment of the atopic dermatitis has shown varying results. We aimed to evaluate whether synbiotic supplementation decrease severity of atopic dermatitis (AD) in childhood. In a randomized double blind-placebo controlled trial, we evaluated the synbiotic supplementation efficiency on the treatment of atopic dermatitis. Infants aged 1-36 months with moderate to severe atopic dermatitis were randomized (n=41) and received either synbiotic (probiotic plus prebiotic) (n=20) or placebo (n=21) daily as a powder for two months. Emollient (Eucerin) and topical corticosteroid (Hydrocortisone) were permitted. Children were scored for severity of atopic dermatitis (SCORAD). Also allergen Skin Prick Tests (SPT), IgE blood level and eosinophil count were measured at first visit. Patients' SCORAD were reevaluated at the end of intervention. We followed 36 out of 41 subjects for two months (drop out rate = 9%). In the whole group, the mean Total SCORAD (at base line 40.93) decreased by 56% (p=0.00). The mean Objective SCORAD (at base line 31.29) decreased by 53% (p=0.00). There was no significant difference in the mean decrease of total SCORAD between placebo (22.3) and synbiotic groups (24.2). There was also no difference between two intervention groups in the mean decrease of total SCORAD regarding to different demographic, clinical and para clinical subgroups. This study could not confirm synbiotic as an effective treatment for childhood atopic dermatitis and further studies are needed. These findings challenge the role of synbiotics in the treatment of childhood atopic dermatitis.

  9. Effects of synbiotics on treatment of children with failure to thrive: A t