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Sample records for placebo controlled phase

  1. Therapy of CF-Patients with Amitriptyline and Placebo - a Randomised, Double-Blind, Placebo-Controlled Phase IIb Multicenter, Cohort-Study

    National Research Council Canada - National Science Library

    Nährlich, Lutz; Mainz, Jochen G; Adams, Constantin; Engel, Corinna; Herrmann, Gloria; Icheva, Vanya; Lauer, Josefine; Deppisch, Caroline; Wirth, Andreas; Unger, Katy; Graepler-Mainka, Ute; Hector, Andreas; Heyder, Susanne; Stern, Martin; Döring, Gerd; Gulbins, Erich; Riethmüller, Joachim

    2013-01-01

    ... and infection susceptibility to pulmonary P. aeruginosa in these mice. To test for a beneficial effect of amitriptyline in vivo, we performed a phase IIb randomised, double-blind, placebo-controlled study...

  2. 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.

  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...... using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability...... worsening were -26 and -66 % as measured using the EDSS (HR 0.742, p = 0.13) and MSFC (p = 0.208), respectively. Adverse events occurred in 75, 82, and 70 % of laquinimod, IFNβ-1a, and placebo patients, respectively. Once-daily oral laquinimod 0.6 mg resulted in statistically nonsignificant reductions...

  4. Luteal Phase Support in the Intrauterine Insemination (IUI Cycles: A Randomized Double Blind, Placebo Controlled Study.

    Directory of Open Access Journals (Sweden)

    Batool Hossein Rashidi

    2014-12-01

    Full Text Available To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG, in sub fertile couples.This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg and hMG (75 IU in preparation for the IUI cycle. Study group (n = 127 received luteal phase support in the form of vaginal progesterone (400 mg twice a day, and control group (n = 126 received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups.The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3. The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45.It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation.

  5. 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.

  6. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    Directory of Open Access Journals (Sweden)

    Dietlind L. Wahner-Roedler

    2011-01-01

    Full Text Available Most patients with fibromyalgia use complementary and alternative medicine (CAM. Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ and the Center for Epidemiologic Studies Depression Scale (CES-D at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02 and by 18% in the placebo group (P < .001. The difference in change in scores between the groups was not significant (P = .16. With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004 and in the placebo group by 15% (P = .05. The change in scores was similar in the groups (P = .83. Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated.

  7. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor

    Science.gov (United States)

    Kavanaugh, Arthur; Mease, Philip J; Gomez-Reino, Juan J; Adebajo, Adewale O; Wollenhaupt, Jürgen; Gladman, Dafna D; Lespessailles, Eric; Hall, Stephen; Hochfeld, Marla; Hu, ChiaChi; Hough, Douglas; Stevens, Randall M; Schett, Georg

    2014-01-01

    Objectives Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. Methods In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. Results At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. Conclusions Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. Clinical trial registration number NCT

  8. Therapy of CF-Patients with Amitriptyline and Placebo - a Randomised, Double-Blind, Placebo-Controlled Phase IIb Multicenter, Cohort-Study

    Directory of Open Access Journals (Sweden)

    Lutz Nährlich

    2013-04-01

    Full Text Available Background/Aims: Several recent studies revealed an accumulation of ceramide in bronchial, tracheal and intestinal epithelial cells of mice and patients with cystic fibrosis (CF. Normalization of ceramide concentrations in lungs of CF mice employing the functional acid sphingomyelinase inhibitor amitriptyline also normalized mucociliary clearance, chronic inflammation and infection susceptibility to pulmonary P. aeruginosa in these mice. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed a phase IIb randomised, double-blind, placebo-controlled study. Twenty-one CF patients were treated with 25 mg/d amitriptyline twice daily for 28 days. The placebo consisted of 19 patients and was also treated twice per day. The primary endpoint was the change in lung function in the intention-to-treat (ITT population. Secondary endpoints were ceramide levels in epithelial cells and safety. Results: After treatment, forced expiratory volume in 1 sec predicted (FEV1 increased 6.3±11.5% (p=0.08 in the ITT population (36 of 40 CF patients and 8.5±10% (p=0.013 in the per protocol (PP population (29 of 40 patients. Ceramide levels decreased in nasal epithelial cells after amitriptyline treatment. Amitriptyline had no severe and only mild and mostly transient adverse effects, i.e. xerostomia and tiredness. Conclusion: Amitriptyline is safe in CF-patients, increases FEV1 and reduces ceramide in lung cells of CF patients.

  9. Vernakalant hydrochloride for rapid conversion of atrial fibrillation - A phase 3, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Roy, D.; Pratt, C.M.; Torp-Pedersen, C.;

    2008-01-01

    Background - The present study assessed the efficacy and safety of vernakalant hydrochloride ( RSD1235), a novel compound, for the conversion of atrial fibrillation ( AF). Methods and Results - Patients were randomized in a 2: 1 ratio to receive vernakalant or placebo and were stratified by AF du...

  10. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

    Science.gov (United States)

    Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

    2015-01-01

    Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS. PMID:25595151

  11. A Phase 3 Placebo-Controlled, Double Blind, Multi-Site Trial of the alpha-2-adrenergic Agonist, Lofexidine, for Opioid Withdrawal

    Science.gov (United States)

    Yu, Elmer; Miotto, Karen; Akerele, Evaristo; Montgomery, Ann; Elkashef, Ahmed; Walsh, Robert; Montoya, Ivan; Fischman, Marian W.; Collins, Joseph; McSherry, Frances; Boardman, Kathy; Davies, David K.; O’Brien, Charles P.; Ling, Walter; Kleber, Herbert; Herman, Barbara H.

    2008-01-01

    Context Lofexidine is an alpha-2-A noradrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. Objective To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally-defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. Design An inpatient, Phase 3, placebo-controlled, double blind, randomized multi-site trial with three phases: (1) Opioid Agonist Stabilization Phase (days 1–3), (2) Detoxification/Medication or Placebo Phase (days 4–8), and (3) Post Detoxification/Medication Phase (days 9–11). Subjects Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. Main Outcome Measure Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (2nd opioid detoxification treatment day). Results Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (Least squares means 19.5 ± 2.1 versus 30.9 ± 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Trial Registration trial registry name A Phase 3 Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal, registration number NCT00032942, URL for the registry http://clinicaltrials.gov/ct/show/NCT00032942?order=4. PMID:18508207

  12. Efficacy and safety of bilastine in Japanese patients with perennial allergic rhinitis: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study

    OpenAIRE

    Kimihiro Okubo; Minoru Gotoh; Mikiya Asako; Yasuyuki Nomura; Michinori Togawa; Akihiro Saito; Takayuki Honda; Yoshihiro Ohashi

    2017-01-01

    Background: Bilastine, a novel non-sedating second-generation H1 antihistamine, has been approved in most European countries since 2010. This study aimed to evaluate the superiority of bilastine over placebo in Japanese patients with perennial allergic rhinitis (PAR). Methods: This randomized, double-blind, placebo-controlled, parallel-group, phase III study (trial registration number JapicCTI-142600) evaluated the effect of a 2-week treatment period with bilastine (20 mg once daily), fexo...

  13. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial.

    Science.gov (United States)

    Steinhoff, Mark C; Katz, Joanne; Englund, Janet A; Khatry, Subarna K; Shrestha, Laxman; Kuypers, Jane; Stewart, Laveta; Mullany, Luke C; Chu, Helen Y; LeClerq, Steven C; Kozuki, Naoko; McNeal, Monica; Reedy, Adriana M; Tielsch, James M

    2017-09-01

    Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17-25 weeks vs 26-34 weeks). Women were eligible if they were married, 15-40 years of age, 17-34 weeks' gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0-180 days postpartum, the incidence of low birthweight (Bill & Melinda Gates Foundation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The efficacy and safety of a nicotine conjugate vaccine (NicVAX®) or placebo co-administered with varenicline (Champix®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial

    National Research Council Canada - National Science Library

    Hoogsteder, Philippe H J; Kotz, Daniel; van Spiegel, Paul I; Viechtbauer, Wolfgang; Brauer, Ruth; Kessler, Paul D; Kalnik, Matthew W; Fahim, Raafat E F; van Schayck, Onno C P

    2012-01-01

    ... its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine...

  15. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Knudsen, Lene Meldgaard; Mylin, Anne Kærsgaard

    2009-01-01

    The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  16. A pollen extract (Cernilton) in patients with inflammatory chronic prostatitis-chronic pelvic pain syndrome: a multicentre, randomised, prospective, double-blind, placebo-controlled phase 3 study.

    Science.gov (United States)

    Wagenlehner, Florian M E; Schneider, Henning; Ludwig, Martin; Schnitker, Jörg; Brähler, Elmar; Weidner, Wolfgang

    2009-09-01

    National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.

  17. 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

    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/m(2) 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...... in the skin of the vitamin K3-treated area compared to the placebo area. CONCLUSION: The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash....

  18. A Randomized, Double-Blind, Single-Dose, Placebo-Controlled, Multicenter, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    Science.gov (United States)

    Rosenberg, Russell P.; Hull, Steven G.; Lankford, D. Alan; Mayleben, David W.; Seiden, David J.; Furey, Sandy A.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objectives: To evaluate the effects of single doses of gabapentin 250 and 500 mg on polysomnographic (PSG) and participant-reported sleep measures in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 500 mg (n = 125), 250 mg (n = 125), or placebo (n = 127) 30 min prior to bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, post-sleep questionnaire, and the Karolinska Sleep Diary (KSD). Next-day residual effects (Digit Symbol Substitution Test [DSST] and Stanford Sleepiness Scale [SSS]) and tolerability were assessed. Results: Demographics were comparable among groups. Among PSG endpoints, wake after sleep onset (primary endpoint) (135.7 [placebo], 100.7 [250 mg], and 73.2 [500 mg] min) was significantly lower and total sleep time (TST) (311.4, 356.5, and 378.7 min) significantly greater in both gabapentin groups versus placebo. Latency to persistent sleep was not significantly different among groups. Percent slow wave sleep (12.6%, 15.4%, and 17.0%, respectively) was significantly greater and percent stage 1 (15.1%, 11.8%, and 10.8%, respectively) significantly lower relative to placebo. Gabapentin was associated with significantly higher values of KSD Sleep Quality Index and reported TST versus placebo; no other reported outcomes were significant. Neither gabapentin dose produced evidence of next-day residual effects as measured by DSST and SSS. Adverse events were infrequent (Rosenberg RP, Hull SG, Lankford DA, Mayleben DW, Seiden DJ, Furey SA, Jayawardena S, Roth T. A randomized, double-blind, single-dose, placebo-controlled, multicenter, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med 2014;10(10):1093-1100. PMID:25317090

  19. Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis

    OpenAIRE

    Miller, Aaron E.; O’Connor, Paul; Wolinsky, Jerry S.; Confavreux, Christian; Kappos, Ludwig; Olsson, Tomas P.; Truffinet, Philippe; Wang, Lin; D’Castro, Laura; Comi, Giancarlo; Freedman, Mark S; ,

    2012-01-01

    Background: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified s...

  20. Topical treatment of CIN 2+ by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study.

    Science.gov (United States)

    Van Pachterbeke, C; Bucella, D; Rozenberg, S; Manigart, Y; Gilles, C; Larsimont, D; Vanden Houte, K; Reynders, M; Snoeck, R; Bossens, M

    2009-10-01

    Randomized controlled trial evaluating a topical treatment for cervical intraepithelial neoplasia 2 and 3 (CIN 2+) using cidofovir. Fifty-three women with a biopsy-proven CIN 2+ were randomly assigned, 6 weeks before their planned conisation, either 3 applications of 3 ml 2% cidofovir in Intrasite gel in a cervical cap or a placebo (the same volume of Intrasite alone). A cervical sample for high-risk types of human papillomaviruses (HPV) (Hybrid Capture 2 or HC2) was taken before treatment and before conisation. The cone was submitted for pathological examination, and subsequently, along with the initial biopsy, to in situ hybridization (ISH) for high-risk HPV. Forty-eight patients were treated and followed according to the protocol, (23 cidofovir, and 25 placebo). Fourteen of the 23 cones were free of any CIN (60.8%) in the cidofovir group. Only 5 of 25 cones were free of any CIN (20%) in the placebo group (ptreatment with cidofovir, at this point, cannot replace conisation, but it is a promising candidate for topical chemotherapy of CIN 2+ lesions; a larger prospective randomized study is needed to confirm our results.

  1. Efficacy of mirtazapine for the treatment of fibromyalgia without concomitant depression: a randomized, double-blind, placebo-controlled phase IIa study in Japan.

    Science.gov (United States)

    Miki, Kenji; Murakami, Masato; Oka, Hiroshi; Onozawa, Kaname; Yoshida, Sadahiro; Osada, Kenichi

    2016-09-01

    To evaluate the efficacy and safety of mirtazapine in Japanese patients with fibromyalgia (FM), a parallel-group, randomized, double-blind, placebo-controlled phase IIa study was conducted at 57 sites between November 2012 and February 2014. Patients aged 20 to 64 years who met the American College of Rheumatology 1990 diagnostic FM criteria and had stably high pain scores during a placebo run-in period were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to receive mirtazapine orally (15 mg/d for 1 week and then 30 mg/d) or matching placebo for 12 weeks. The primary endpoint was change in mean numerical rating scale (NRS) pain score from baseline to endpoint (week 12 or early discontinuation). Of the 430 patients randomized (n = 215 each group), 422 (n = 211 each group) were analyzed for the primary endpoint. At the study endpoint, mirtazapine caused a significantly greater reduction in the mean NRS pain score compared with placebo (difference, 0.44; 95% confidence interval, -0.72 to -0.17; P = 0.0018). The reduction by mirtazapine remained significantly greater compared with placebo from week 6 onward. More patients treated with mirtazapine had their NRS pain score reduced by ≥30% from baseline (45.5% vs 30.8%). Mirtazapine also improved pain-related quality of life assessed by the Japanese version of the Fibromyalgia Impact Questionnaire and the Short-Form 36 Questionnaire. Adverse events were more common with mirtazapine than placebo (68.8% vs 56.7%), including somnolence (32.1% vs 7.4%), weight gain (17.7% vs 0.9%), and increased appetite (11.6% vs 3.3%). In conclusion, mirtazapine was an effective and safe treatment for Japanese patients with FM.

  2. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Kim, Sung-Bae; Dent, Rebecca; Im, Seock-Ah; Espié, Marc; Blau, Sibel; Tan, Antoinette R; Isakoff, Steven J; Oliveira, Mafalda; Saura, Cristina; Wongchenko, Matthew J; Kapp, Amy V; Chan, Wai Y; Singel, Stina M; Maslyar, Daniel J; Baselga, José

    2017-10-01

    The oral AKT inhibitor ipatasertib is being investigated in cancers with a high prevalence of PI3K/AKT pathway activation, including triple-negative breast cancer. The LOTUS trial investigated the addition of ipatasertib to paclitaxel as first-line therapy for triple-negative breast cancer. In this randomised, placebo-controlled, double-blind, phase 2 trial, women aged 18 years or older with measurable, inoperable, locally advanced or metastatic triple-negative breast cancer previously untreated with systemic therapy were recruited from 44 hospitals in South Korea, the USA, France, Spain, Taiwan, Singapore, Italy, and Belgium. Enrolled patients were randomly assigned (1:1) to receive intravenous paclitaxel 80 mg/m(2) (days 1, 8, 15) with either ipatasertib 400 mg or placebo once per day (days 1-21) every 28 days until disease progression or unacceptable toxicity. Randomisation was by stratified permuted blocks (block size of four) using an interactive web-response system with three stratification criteria: previous (neo)adjuvant therapy, chemotherapy-free interval, and tumour PTEN status. The co-primary endpoints were progression-free survival in the intention-to-treat population and progression-free survival in the PTEN-low (by immunohistochemistry) population. This ongoing trial is registered with ClinicalTrials.gov (NCT02162719). Between Sept 2, 2014, and Feb 4, 2016, 166 patients were assessed for eligibility and 124 patients were enrolled and randomly assigned to paclitaxel plus ipatasertib (n=62) or paclitaxel plus placebo (n=62). Median follow-up was 10·4 months (IQR 6·5-14·1) in the ipatasertib group and 10·2 months (6·0-13·6) in the placebo group. Median progression-free survival in the intention-to-treat population was 6·2 months (95% CI 3·8-9·0) with ipatasertib versus 4·9 months (3·6-5·4) with placebo (stratified hazard ratio [HR] 0·60, 95% CI 0·37-0·98; p=0·037) and in the 48 patients with PTEN-low tumours, median progression

  3. Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study.

    Science.gov (United States)

    O'Donnell, Colin P; Allott, Kelly A; Murphy, Brendan P; Yuen, Hok Pan; Proffitt, Tina-Marie; Papas, Alicia; Moral, Jennifer; Pham, Tee; O'Regan, Michaela K; Phassouliotis, Christina; Simpson, Raelene; McGorry, Patrick D

    2016-12-01

    Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder. 121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009. Patients taking low-dose antipsychotic medication were randomly assigned to receive once-daily taurine 4 g or placebo for 12 weeks. The coprimary outcomes were change in symptomatology (measured by the Brief Psychiatric Rating Scale [BPRS] total score) and change in cognition (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery composite score) at 12 weeks. Secondary outcomes included tolerability and safety and additional clinical and functioning measures. 86 participants (n = 47 taurine; n = 39 placebo) were included in the final analysis. Taurine significantly improved symptomatology measured by the BPRS total score (95% CI, 1.8-8.5; P = .004) and psychotic subscale (95% CI, 0.1-1.5; P = .026) compared to placebo. Additionally, improvements were observed in the Calgary Depression Scale for Schizophrenia (95% CI, 0.1-3.0; P = .047) and Global Assessment of Functioning (95% CI, 0.3-8.8; P = .04) scores. There was no group difference in composite cognitive score (95% CI, -1.7 to 1.0; P = .582). A significant group difference was found on one safety and tolerability item (psychic item 2, asthenia/lassitude/increased fatigability) of the Udvalg for Kliniske Undersogelser, with the taurine group showing a

  4. A randomized, double blind, placebo-controlled, multicenter phase II trial of Allisartan Isoproxil in essential hypertensive population at low-medium risk.

    Science.gov (United States)

    Li, Ying; Li, Xiao-hui; Huang, Zhi-jun; Yang, Guo-ping; Zhang, Guo-gang; Zhao, Shui-ping; Guo, Ying; Lu, Shi-juan; Ma, Jian-lin; Meng, Fan-bo; Chen, Ping; Yuan, Hong

    2015-01-01

    Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk. A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (Psafety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study. Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk. http://www.chictr.org/cn/ ChiCTR-TRC-10000886.

  5. A randomized, double blind, placebo-controlled, multicenter phase II trial of Allisartan Isoproxil in essential hypertensive population at low-medium risk.

    Directory of Open Access Journals (Sweden)

    Ying Li

    Full Text Available Angiotensin II receptor blockers (ARBs is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R, in essential hypertensive patients at low-medium risk.A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P0.05. No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study.Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk.http://www.chictr.org/cn/ ChiCTR-TRC-10000886.

  6. Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

    Directory of Open Access Journals (Sweden)

    Maneeton Narong

    2012-09-01

    Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

  7. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans E.; Meldgaard Knudsen, Lene; Mylin, Anne K.;

    2009-01-01

    The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conlusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...... toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p

  8. A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007.

    Directory of Open Access Journals (Sweden)

    Ian McGowan

    Full Text Available OBJECTIVE: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal, adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. METHODS: Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein, microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. RESULTS: Sixty-five participants (45 men and 20 women were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability was 87% (reduced glycerin formulation of tenofovir 1% gel, 93% (hydroxyethyl cellulose placebo gel, and 63% (nonoxynol-9 gel. Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. CONCLUSIONS: The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. TRIAL REGISTRATION: ClinicalTrials.gov NCT01232803.

  9. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial.

    Science.gov (United States)

    Rastelli, Antonella L; Taylor, Marie E; Gao, Feng; Armamento-Villareal, Reina; Jamalabadi-Majidi, Shohreh; Napoli, Nicola; Ellis, Matthew J

    2011-08-01

    A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20-29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10-19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baseline musculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.

  10. Immunogenicity and safety of a tetravalent dengue vaccine in healthy adults in India: A randomized, observer-blind, placebo-controlled phase II trial.

    Science.gov (United States)

    Dubey, Anand Prakash; Agarkhedkar, Sharad; Chhatwal, Jugesh; Narayan, Arun; Ganguly, Satyabrata; Wartel, T Anh; Bouckenooghe, Alain; Menezes, Josemund

    2016-01-01

    Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo-controlled, Phase II study, adults aged 18-45 years were randomized 2:1 to receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration. Immunogenicity was assessed using a 50% plaque reduction neutralization test (PRNT50) at baseline and 28 days after each study injection. 189 participants were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%. Seropositivity rates for each serotype increased after each CYD-TDV injection with a more pronounced increase after the first injection. In the CYD-TDV group, geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third injection compared with baseline but remained similar to baseline in the placebo group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to 24.6-fold higher after the third injection compared with baseline in those who were dengue seropositive and dengue seronegative, respectively. Pain was the most commonly reported solicited injection site reaction after the first injection in both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently after subsequent injections. No serious adverse events were vaccine-related, no immediate unsolicited adverse events, and no virologically-confirmed cases of dengue, were reported during the study. The immunogenicity and safety of CYD-TDV was satisfactory in both dengue seropositive and seronegative Indian adults.

  11. Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked, multicenter, placebo-controlled phase II study.

    Science.gov (United States)

    Kinoshita, Shigeru; Awamura, Saki; Oshiden, Kazuhide; Nakamichi, Norihiro; Suzuki, Hiroyuki; Yokoi, Norihiko

    2012-12-01

    To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye. A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study. A total of 308 patients with dry eye. After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks. The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score. Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups. Rebamipide was effective in

  12. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

    Science.gov (United States)

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-01-01

    Summary Background Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of

  13. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

    Science.gov (United States)

    Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

    2013-12-02

    Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All

  14. Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies.

    Science.gov (United States)

    Goel, Gautam; King, Tim; Daveson, A James; Andrews, Jane M; Krishnarajah, Janakan; Krause, Richard; Brown, Gregor J E; Fogel, Ronald; Barish, Charles F; Epstein, Roger; Kinney, Timothy P; Miner, Philip B; Tye-Din, Jason A; Girardin, Adam; Taavela, Juha; Popp, Alina; Sidney, John; Mäki, Markku; Goldstein, Kaela E; Griffin, Patrick H; Wang, Suyue; Dzuris, John L; Williams, Leslie J; Sette, Alessandro; Xavier, Ramnik J; Sollid, Ludvig M; Jabri, Bana; Anderson, Robert P

    2017-07-01

    A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet. We did two randomised, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and the USA, in HLA-DQ2·5-positive patients aged 18-70 years who had coeliac disease and were on a gluten-free diet. In the screening period for ascending dose cohorts, participants were randomly assigned (1:1) by central randomisation with a simple block method to a double-blind crossover, placebo-controlled oral gluten challenge. Participants with a negative interferon γ release assay to Nexvax2 peptides after the screening oral gluten challenge were discontinued before dosing. For the biopsy cohorts, the screening period included an endoscopy, and participants with duodenal histology who had a Marsh score of greater than 1 were discontinued before dosing. Participants were subsequently randomly assigned to either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts (1:1) by central randomisation with a simple block method. In the three-dose study, participants received either Nexvax2 60 μg, 90 μg, or 150 μg weekly, or placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2 at the maximum tolerated dose (MTD) or placebo. In the 16-dose study, participants received Nexvax2 150 μg or 300 μg or placebo twice weekly over 53 days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD or placebo. In the 4-week post

  15. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration.

    Science.gov (United States)

    Brooker, Sonja; Martin, Susan; Pearson, Ann; Bagchi, Debasis; Earl, Judith; Gothard, Lone; Hall, Emma; Porter, Lucy; Yarnold, John

    2006-04-01

    Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n = 44) or placebo (n = 22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm(2)) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. At 12 months post-randomisation, > or =50% reduction in surface area (cm(2)) of breast induration was recorded in 13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. The study failed to show efficacy of orally-administered GSPE in patients with breast induration following radiotherapy for breast cancer.

  16. Lovastatin as an Adjuvant to Lithium for Treating Manic Phase of Bipolar Disorder: A 4-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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    Ahmad Ghanizadeh

    2014-01-01

    Full Text Available Objectives. Many patients with bipolar disorder suffer from metabolic disorder. Lovastatin is effective for treating major depression. This double-blind randomized placebo controlled clinical trial investigates whether lovastatin is a useful adjuvant to lithium for treating mania. Methods. Fifty-four patients with bipolar disorder-manic phase were randomly allocated into lovastatin or placebo group. The clinical symptoms were assessed at baseline, week 2, and week 4 using Young Mania Rating Scale. Adverse effects were checked. Results. Forty-six out of 54 patients completed this trial. The mania score in the lovastatin group decreased from 40.6 (11.1 at baseline to 12.9 (8.7 and 4.1 (5.4 at weeks 2 and 4, respectively. The score in the placebo group decreased from 41.0 (11.2 at baseline to 12.8 (8.07 and 5.8 (4.6 at weeks 2 and 4, respectively. However, there was no significant difference between groups at week 2 and week 4. The adverse effects rates were comparable between the two groups. No serious adverse effect was found. Tremor and nausea were the most common adverse effects. Conclusions. Lovastatin neither exacerbated nor decreased the symptoms of mania in patients with bipolar disorder. Current results support that the combination of lovastatin with lithium is tolerated well in bipolar disorder. The trial was registered with the Iranian Clinical Trials Registry (IRCT201302203930N18.

  17. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials.

    Science.gov (United States)

    Reich, Kristian; Papp, Kim A; Blauvelt, Andrew; Tyring, Stephen K; Sinclair, Rodney; Thaçi, Diamant; Nograles, Kristine; Mehta, Anish; Cichanowitz, Nicole; Li, Qing; Liu, Kenneth; La Rosa, Carmen; Green, Stuart; Kimball, Alexa B

    2017-07-15

    Tildrakizumab is a high-affinity, humanised, IgG1 κ antibody targeting interleukin 23 p19 that represents an evolving treatment strategy in chronic plaque psoriasis. Previous research suggested clinical improvement with inhibition of interleukin 23 p19. We did two phase 3 trials to investigate whether tildrakizumab is superior to placebo and etanercept in the treatment of chronic plaque psoriasis. We did two three-part, parallel group, double-blind, randomised controlled studies, reSURFACE 1 (at 118 sites in Australia, Canada, Japan, the UK, and the USA) and reSURFACE 2 (at 132 sites in Europe, Israel, and the USA). Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis (body surface area involvement ≥10%, Physician's Global Assessment [PGA] score ≥3, and Psoriasis Area and Severity Index [PASI] score ≥12) were randomised (via interactive voice and web response system) to tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo in reSURFACE 1 (2:2:1), or to tildrakizumab 200 mg, tildrakizumab 100 mg, placebo, or etanercept 50 mg (2:2:1:2). Randomisation was done by region and stratified for bodyweight (≤90 kg or >90 kg) and previous exposure to biologics therapy for psoriasis. Investigators, participants, and study personnel were blinded to group allocation and remained blinded until completion of the studies. Assigned medication was identical in appearance and packaging. Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 (weeks 12 and 16 for participants re-randomised from placebo to tildrakizumab; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2). The co-primary endpoints were the proportion of patients achieving PASI 75 and PGA response (score of 0 or 1 with ≥2 grade score reduction from baseline) at week 12. Safety was assessed in the all-participants-as-treated population, and efficacy in the full-analysis set. These trials are

  18. Lanreotide Autogel 90 mg and lymphorrhea prevention after axillary node dissection in breast cancer: a phase III double blind, randomized, placebo-controlled trial.

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    Gauthier, T; Garuchet-Bigot, A; Marin, B; Mollard, J; Loum, O; Fermeaux, V; Jammet, I; Kanoun, D; Maubon, A; Aubard, Y

    2012-10-01

    The aim of this study was to assess the efficacy of Lanreotide Autogel 90 mg PR to prevent lymphorrhea after axillary dissection in breast cancer. A Phase III double-blind, randomized, placebo-controlled trial was performed between April 1st, 2008, and December 31st, 2010. The primary endpoint was the lymphorrhea volume (ml) in the axillary drain during the first four postoperative days. The secondary end points were the number of days until axillary drain removal, hospital stay duration (days), lymphorrhea volume (ml) up to days 15, 30 and 180, number of cases with seroma aspiration and number of seroma aspirations, evaluation of wound, arm pain and mobility on days 15, 30 and 180. A total of 148 patients were recruited for the study. Altogether 145 patients were randomized and analysed on an intention-to-treat basis. On the day before surgery 73 patients received the placebo and 72 patients received lanreotide. At four postoperative days, there was a tendency towards a reduction of the lymphorrhea volume in the lanreotide group (median 292 ml, range 1-965 ml) as compared to the placebo group (median 337 ml, range 0-1230 ml), although it was not statistically significant (p = 0.18). There was no significant difference for the secondary end points. In the group with axillary dissection performed alone (n = 24), the lymphorrhea volume was shown to be significantly reduced in the lanreotide group, (p = 0.035) as compared to the placebo group. Our study did not identify any overall significant reduction of lymphorrhea on lanreotide. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Safety and efficacy of MIM D3 ophthalmic solutions in a randomized placebo controlled Phase 2 clinical trial in patients with dry eye

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    Meerovitch K

    2013-06-01

    Full Text Available Karen Meerovitch,1 Gail Torkildsen,2 John Lonsdale,3 Heidi Goldfarb,4 Teresa Lama,1 Garth Cumberlidge,1 George W Ousler III5 1Mimetogen Pharmaceuticals Inc, Montreal, QC, Canada; 2Andover Eye Associates, Andover, MA, USA; 3Central Maine Eye Care, Lewiston, ME, USA; 4SDC, Tempe, AZ, USA; 5Ora Inc, Andover, MA, USA Purpose: To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye. Design: A prospective, two-center, randomized, double-masked, placebo-controlled Phase 2 study. Methods: A total of 150 dry eye patients were randomized 1:1:1 to study medication (1% MIM-D3, 5% MIM-D3, or placebo and dosed twice daily (BID for 28 days. Key eligibility criteria included exacerbation in corneal staining and ocular discomfort in the Controlled Adverse Environment (CAESM on two visits, separated by 1 week of BID dosing with artificial tears. Safety and efficacy were evaluated at baseline, throughout treatment, and for 2 weeks post-treatment. The pre-specified primary outcome measures were fluorescein corneal staining post-CAE at day 28 and diary worst symptom scores over 28 days. Secondary outcomes included the pre-, post-, and the change from pre- to post-CAE fluorescein and lissamine green staining in both corneal and conjunctival regions, as well as individual diary symptoms. Results: The prespecified primary endpoints were not met. Compared with placebo, fluorescein corneal staining at day 28 was significantly improved (P < 0.05 in the 1% MIM-D3 group for the assessment of change from pre-CAE to post-CAE. In addition, following CAE exposure, patients in the 1% MIM-D3 group showed significant improvements versus placebo (P < 0.05 in inferior fluorescein and lissamine green staining after 14 and 28 days. Compared with placebo, patients in the 5% MIM-D3 group reported significantly lower daily diary scores for ocular dryness (P < 0.05. In a subgroup defined by higher symptom scores during

  20. Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study

    NARCIS (Netherlands)

    Vries, M. de; Rijckevorsel, D.C.M. van; Vissers, K.C.P.; Wilder-Smith, O.H.G.; Goor, H. van

    2017-01-01

    BACKGROUND & AIMS: Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and

  1. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial.

    Science.gov (United States)

    Knoller, Nachshon; Levi, Leon; Shoshan, Igal; Reichenthal, Eli; Razon, Nissim; Rappaport, Zvi H; Biegon, Anat

    2002-03-01

    To establish the safety of intravenous dexanabinol in severe head injury. Prospective, randomized, double-blind, placebo- (vehicle) controlled, multicenter, escalating dose study of a single administration of drug (48 or 150 mg) or vehicle (1 or 3 mL). All Israeli neurosurgical intensive care units (a total of six units). Sixty-seven patients, aged 16-65 yrs, Glasgow Coma Scale score of 4-8, injured within 6 hrs of treatment. Intracranial pressure, cerebral perfusion pressure, blood pressure, and heart rate were measured continuously in the intensive care unit. Adverse medical events were recorded and clinical outcome was assessed by the Glasgow outcome scale throughout a 6-month follow-up period. A highly significant reduction in the percentage of time with intracranial pressure >25, cerebral perfusion pressure <50, and systolic blood pressure <90 mm Hg was observed in the drug-treated group. The nature and incidence of adverse medical events were similar in the two groups. The percentage of patients achieving good neurologic outcome on the Glasgow outcome scale was 21% and 14% higher in the drug-treated group at 3 and 6 months, respectively. Statistical analysis of these differences by a logistic model using dose, entry Glasgow coma scale score, and computed tomograph as covariates yielded p values for the effect of treatment of .03 and .14 at 3 and 6 months, respectively. Dexanabinol was safe and well tolerated in severe head injury. The treated patients achieved significantly better intracranial pressure/cerebral perfusion pressure control without jeopardizing blood pressure. A trend toward faster and better neurologic outcome was also observed.

  2. Placebo-Controlled Trials, Ethics of

    NARCIS (Netherlands)

    van der Graaf, R; Rid, Annette

    2015-01-01

    There are often good scientific and ethical reasons for using placebo controls in clinical trials. At the same time placebo use is controversial, especially when an established effective treatment is being withheld from the control group. This article gives an overview of the key ethical positions

  3. Placebo-Controlled Trials, Ethics of

    NARCIS (Netherlands)

    van der Graaf, R; Rid, Annette

    2015-01-01

    There are often good scientific and ethical reasons for using placebo controls in clinical trials. At the same time placebo use is controversial, especially when an established effective treatment is being withheld from the control group. This article gives an overview of the key ethical positions i

  4. Phase I randomized dose-ascending placebo-controlled trials of ferroquine - a candidate anti-malarial drug - in adults with asymptomatic Plasmodium falciparum infection

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    Ospina Salazar Carmen L

    2011-03-01

    Full Text Available Abstract Background The development and spread of drug resistant Plasmodium falciparum strains is a major concern and novel anti-malarial drugs are, therefore, needed. Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P. falciparum laboratory strains. Methods Adult young male aged 18 to 45 years, asymptomatic carriers of P. falciparum, were included in two-dose escalation, double-blind, randomized, placebo-controlled Phase I trials, a single dose study and a multiple dose study aiming to evaluate oral doses of ferroquine from 400 to 1,600 mg. Results Overall, 54/66 patients (40 and 26 treated in the single and multiple dose studies, respectively experienced at least one adverse event, 15 were under placebo. Adverse events were mainly gastrointestinal symptoms such as abdominal pain (16, diarrhoea (5, nausea (13, and vomiting (9, but also headache (11, and dizziness (5. A few patients had slightly elevated liver parameters (10/66 including two patients under placebo. Moderate changes in QTc and morphological changes in T waves were observed in the course of the study. However, no adverse cardiac effects with clinical relevance were observed. Conclusions These phase I trials showed that clinically, ferroquine was generally well-tolerated up to 1,600 mg as single dose and up to 800 mg as repeated dose in asymptomatic young male with P. falciparum infection. Further clinical development of ferroquine, either alone or in combination with another anti-malarial, is highly warranted and currently underway.

  5. RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.

    Science.gov (United States)

    England, Timothy J; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M

    2017-05-01

    Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (P=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P=0.04); RIC augmented plasma HSP27 (heat shock protein 27; Pacute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015. © 2017 American Heart Association, Inc.

  6. Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.

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    Eiichiro Nagata

    Full Text Available Bromocriptine mesylate (BRC, a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS Here we report a first in human trial in ALS.A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7. The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint and upon completion or discontinuation of the study (2nd endpoint of the dosing.Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%, eating and drinking (P = 2.2%, ALSFRS-R total (P = 17.6%, grip strength (P = 19.8% compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%, ALSAQ40-communication (P = 11.9%, eating and drinking (P = 13.6%, and neck forward-bent test (P = 15.4% of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.UMIN Clinical Trials UMIN000008527.

  7. Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial.

    Science.gov (United States)

    Low, Jenny G; Sung, Cynthia; Wijaya, Limin; Wei, Yuan; Rathore, Abhay P S; Watanabe, Satoru; Tan, Boon Hian; Toh, Liying; Chua, Lian Tee; Hou, Yan'an; Chow, Angelia; Howe, Shiqin; Chan, Wing Ki; Tan, Kah Hin; Chung, Jasmine S; Cherng, Benjamin P; Lye, David C; Tambayah, Paul A; Ng, Lee Ching; Connolly, John; Hibberd, Martin L; Leo, Yee Sin; Cheung, Yin Bun; Ooi, Eng Eong; Vasudevan, Subhash G

    2014-08-01

    Dengue infection is the most common mosquito-borne viral disease worldwide, but no suitable antiviral drugs are available. We tested the α-glucosidase inhibitor celgosivir as a treatment for acute dengue fever. To establish eligibility for inclusion in a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial, individuals aged 21-65 years who had had a fever (≥38°C) for less than 48 h, met at least two criteria indicating probable dengue infection, and had a positive result on a dengue point-of-care test kit or PCR assay were referred for screening at a centre in Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we randomly assigned patients who met full inclusion criteria after screening (1:1; random permuted block length four) to celgosivir (initial 400 mg loading dose within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine doses) or matched placebo. Patients and the entire study team were masked to group assignment. The primary endpoints were mean virological log reduction (VLR) from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a temperature above 37°C from 0 h to 96 h. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01619969. We screened 69 patients and randomly assigned 50 (24 to celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (-1·86, SD 1·07) than in the placebo group (-1·64, 0·75), but the difference was non-significant (-0·22, 90% CI -0·65 to 0·22; one-sided p=0·203). The mean AUC was also higher in the celgosivir group (54·92, SD 31·04) than in the placebo group (40·72, 18·69), but again the difference was non-significant (14·20, 90% CI 2·16-26·25; one-sided p=0·973). We noted similar incidences of adverse events between groups. Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with

  8. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.

    Science.gov (United States)

    Garcia, Esther; Robert, Marta; Peris, Francesc; Nakamura, Hiroshi; Sato, Noriko; Terazawa, Yoshikatsu

    2009-01-01

    Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of

  9. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

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    de Visser Marianne

    2009-11-01

    Full Text Available Abstract Background High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-Tooth type 1A patients and whether this treatment is safe. Methods Patients below age 25 years were randomly assigned to receive placebo or ascorbic acid (one gram twice daily in a double-blind fashion during one year. The primary outcome measure was the change over time in motor nerve conduction velocity of the median nerve. Secondary outcome measures included changes in minimal F response latencies, compound muscle action potential amplitude, muscle strength, sensory function, Charcot-Marie-Tooth neuropathy score, and disability. Results There were no significant differences between the six placebo-treated (median age 16 years, range 13 to 24 and the five ascorbic acid-treated (19, 14 to 24 patients in change in motor nerve conduction velocity of the median nerve (mean difference ascorbic acid as opposed to placebo treatment of 1.3 m/s, confidence interval -0.3 to 3.0 m/s, P = 0.11 or in change of any of the secondary outcome measures over time. One patient in the ascorbic acid group developed a skin rash, which led to discontinuation of the study medication. Conclusion Oral high dose ascorbic acid for one year did not improve myelination of the median nerve in young Charcot-Marie-Tooth type 1A patients. Treatment was relatively safe. Trial registration Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635.

  10. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    McDonald, Craig M; Campbell, Craig; Torricelli, Ricardo Erazo; Finkel, Richard S; Flanigan, Kevin M; Goemans, Nathalie; Heydemann, Peter; Kaminska, Anna; Kirschner, Janbernd; Muntoni, Francesco; Osorio, Andrés Nascimento; Schara, Ulrike; Sejersen, Thomas; Shieh, Perry B; Sweeney, H Lee; Topaloglu, Haluk; Tulinius, Már; Vilchez, Juan J; Voit, Thomas; Wong, Brenda; Elfring, Gary; Kroger, Hans; Luo, Xiaohui; McIntosh, Joseph; Ong, Tuyen; Riebling, Peter; Souza, Marcio; Spiegel, Robert J; Peltz, Stuart W; Mercuri, Eugenio

    2017-07-17

    Duchenne muscular dystrophy (DMD) is a severe, progressive, and rare neuromuscular, X-linked recessive disease. Dystrophin deficiency is the underlying cause of disease; therefore, mutation-specific therapies aimed at restoring dystrophin protein production are being explored. We aimed to assess the efficacy and safety of ataluren in ambulatory boys with nonsense mutation DMD. We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 54 sites in 18 countries located in North America, Europe, the Asia-Pacific region, and Latin America. Boys aged 7-16 years with nonsense mutation DMD and a baseline 6-minute walk distance (6MWD) of 150 m or more and 80% or less of the predicted normal value for age and height were randomly assigned (1:1), via permuted block randomisation (block size of four) using an interactive voice-response or web-response system, to receive ataluren orally three times daily (40 mg/kg per day) or matching placebo. Randomisation was stratified by age (PTC Therapeutics employees, and all other study personnel were masked to group allocation until after database lock. The primary endpoint was change in 6MWD from baseline to week 48. We additionally did a prespecified subgroup analysis of the primary endpoint, based on baseline 6MWD, which is reflective of anticipated rates of disease progression over 1 year. The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01826487. Between March 26, 2013, and Aug 26, 2014, we randomly assigned 230 patients to receive ataluren (n=115) or placebo (n=115); 228 patients comprised the intention-to-treat population. The least-squares mean change in 6MWD from baseline to week 48 was -47·7 m (SE 9·3) for ataluren-treated patients and -60·7 m (9·3) for placebo-treated patients (difference 13·0 m [SE 10·4], 95% CI -7·4 to 33·4; p=0·213). The least-squares mean change for ataluren versus placebo in the prespecified subgroups was -7

  11. Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset.

    Science.gov (United States)

    Nagtegaal, J E; Kerkhof, G A; Smits, M G; Swart, A C; Van Der Meer, Y G

    1998-06-01

    In a double-blind placebo-controlled cross-over study, 30 patients with Delayed Sleep Phase Syndrome (DSPS) were included, of whom 25 finished the study. Melatonin 5 mg was administered during two weeks in a double-blind setting and two weeks in an open setting successively or interrupted by two week of placebo. The study's impact was assessed by measurements of the 24-h curves of endogenous melatonin production and rectal temperature (n = 14), polysomnography (n = 22), actigraphy (n = 13), sleep log (n = 22), and subjective sleep quality (n = 25). Mean dim light melatonin onset (DLMO) (+/- SD), before treatment, occurred at 23.17 hours (+/- 138 min). Melatonin was administered five hours before the individual DLMO. After treatment, the onset of the nocturnal melatonin profile was significantly advanced by approximately 1.5 hour. Body temperature trough did not advance significantly. During melatonin use, actigraphy showed a significant advance of sleep onset and polysomnography, a significant decreased sleep latency. Sleep architecture was not influenced. During melatonin treatment patients felt significantly more refreshed in the morning. These results show that analysis of DLMO of patients suffering from DSPS is important both for diagnosis and therapy. These results are discussed in terms of the biochemistry of the pineal.

  12. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial.

    Science.gov (United States)

    Haffizulla, Jason; Hartman, Aaron; Hoppers, Melanie; Resnick, Harvey; Samudrala, Steve; Ginocchio, Christine; Bardin, Matthew; Rossignol, Jean-François

    2014-07-01

    Influenza is an important cause of morbidity and mortality worldwide. Treatment options are scarce, and new drugs with novel mechanisms of action are needed. We aimed to assess the efficacy and safety of nitazoxanide, a thiazolide anti-infective, for treatment of acute uncomplicated influenza. We did a double-blind, randomised, placebo-controlled, phase 2b/3 trial in 74 primary care clinics in the USA between Dec 27, 2010, and April 30, 2011. We enrolled participants aged 12-65 years with fever, at least one respiratory symptom, and one constitutional symptom of influenza within 48 h of symptom onset. We randomly assigned participants to receive either nitazoxanide 600 mg, nitazoxanide 300 mg, or placebo twice daily for 5 days, (ratio 1:1:1) and followed them up for 28 days. Randomisation lists were computer generated and done in blocks of three. Sponsor, investigators, study monitors, patients, and laboratory personnel were all masked to treatment allocation in the study. The primary endpoint was the time from first dose to alleviation of symptoms. The primary analysis was by intention-to-treat for participants with influenza infection confirmed by RT-PCR or culture at baseline. This trial is registered with ClinicalTrials.gov, number NCT01227421. Of 650 participants screened, 624 (96%) were enrolled. Of these, 212 were randomly assigned to receive placebo twice a day, 201 to receive nitazoxanide 300 mg twice a day, and 211 to receive nitazoxanide 600 mg a day. The median duration of symptoms for participants receiving placebo was 116·7 h (95% CI 108·1-122·1) compared with 95·5 h (84·0-108·0; p=0·0084) for those receiving 600 mg nitazoxanide and 109·1 h (96·1-129·5, p=0·52) for those receiving 300 mg nitazoxanide. Adverse events were similar between the three groups, the most common being headache reported by 24 (11%) of 212 patients enrolled in placebo group, 12 (6%) of 201 patients in the low-dose group, and 17 (8%) of 211 patients in the high

  13. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.

    Directory of Open Access Journals (Sweden)

    Pablo Tebas

    Full Text Available BACKGROUND: Neurokinin-1 receptor (NK1R antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. METHODS: We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml and randomized within each stratum to receive aprepitant at 125 mg QD(Low, or 250 mg QD(High, or placebo(PL for 14 days, and followed for 42 days. RESULTS: Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low, 250 (High, and PL groups. 63% were male; 37% white; mean (SD age 43 (9.3 years. Geometric mean baseline viral load (copies/ml for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20, -0.05(-0.21,+0.10, and +0.04(-0.08,+0.16, respectively. The number of subjects with AEs was 4(44.4%, 5(62.5%, and 1(10% for Low, High, and PL. No Grade 4 AEs occurred. CONCLUSIONS: Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00428519.

  14. WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study.

    Directory of Open Access Journals (Sweden)

    Afif Ben Salah

    Full Text Available BACKGROUND: Cutaneous leishmaniasis (cl is a disfiguring disease that confronts clinicians with a quandary: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France. METHODS: A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50 followed by complete re-epithelialization by D100, and no relapse through D180. RESULTS: Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%. In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94% met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71% [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity. CONCLUSION: Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00703924.

  15. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Novak, Petr; Schmidt, Reinhold; Kontsekova, Eva; Zilka, Norbert; Kovacech, Branislav; Skrabana, Rostislav; Vince-Kazmerova, Zuzana; Katina, Stanislav; Fialova, Lubica; Prcina, Michal; Parrak, Vojtech; Dal-Bianco, Peter; Brunner, Martin; Staffen, Wolfgang; Rainer, Michael; Ondrus, Matej; Ropele, Stefan; Smisek, Miroslav; Sivak, Roman; Winblad, Bengt; Novak, Michal

    2017-02-01

    Neurofibrillary pathology composed of tau protein is a main correlate of cognitive impairment in patients with Alzheimer's disease. Immunotherapy targeting pathological tau proteins is therefore a promising strategy for disease-modifying treatment of Alzheimer's disease. We have developed an active vaccine, AADvac1, against pathological tau proteins and assessed it in a phase 1 trial. We did a first-in-man, phase 1, 12 week, randomised, double-blind, placebo-controlled study of AADvac1 with a 12 week open-label extension in patients aged 50-85 years with mild-to-moderate Alzheimer's disease at four centres in Austria. We randomly assigned patients with a computer-generated sequence in a 4:1 ratio overall to receive AADvac1 or placebo. They received three subcutaneous doses of AADvac1 or placebo from masked vaccine kits at monthly intervals, and then entered the open-label phase, in which all patients were allocated to AADvac1 treatment and received another three doses at monthly intervals. Patients, carers, and all involved with the trial were masked to treatment allocation. The primary endpoint was all-cause treatment-emergent adverse events, with separate analyses for injection site reactions and other adverse events. We include all patients who received at least one dose of AADvac1 in the safety assessment. Patients who had a positive IgG titre against the tau peptide component of AADvac1 at least once during the study were classified as responders. The first-in-man study is registered with EU Clinical Trials Register, number EudraCT 2012-003916-29, and ClinicalTrials.gov, number NCT01850238; the follow-up study, which is ongoing, is registered with EU Clinical Trials Register, number EudraCT 2013-004499-36, and ClinicalTrials.gov, number NCT02031198. This study was done between June 9, 2013, and March 26, 2015. 30 patients were randomly assigned in the double-blind phase: 24 patients to the AADvac1 group and six to the placebo group. A total of 30 patients

  16. Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical).

    Science.gov (United States)

    Kopelman, Peter; Groot, Gerrit de H; Rissanen, Aila; Rossner, Stephan; Toubro, Soren; Palmer, Richard; Hallam, Rob; Bryson, Andrew; Hickling, Roger I

    2010-01-01

    The objective of this multicenter, randomized, double-blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2-week run-in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA(1c)) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.

  17. Randomized, Double-Blind, Placebo-Controlled, Phase III Chemoprevention Trial of Selenium Supplementation in Patients With Resected Stage I Non–Small-Cell Lung Cancer: ECOG 5597

    Science.gov (United States)

    Karp, Daniel D.; Lee, Sandra J.; Keller, Steven M.; Wright, Gail Shaw; Aisner, Seena; Belinsky, Steven Alan; Johnson, David H.; Johnston, Michael R.; Goodman, Gary; Clamon, Gerald; Okawara, Gordon; Marks, Randolph; Frechette, Eric; McCaskill-Stevens, Worta; Lippman, Scott M.; Ruckdeschel, John; Khuri, Fadlo R.

    2013-01-01

    Purpose Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non–small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients and Methods Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. Results The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. Conclusion Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC. PMID:24002495

  18. Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597.

    Science.gov (United States)

    Karp, Daniel D; Lee, Sandra J; Keller, Steven M; Wright, Gail Shaw; Aisner, Seena; Belinsky, Steven Alan; Johnson, David H; Johnston, Michael R; Goodman, Gary; Clamon, Gerald; Okawara, Gordon; Marks, Randolph; Frechette, Eric; McCaskill-Stevens, Worta; Lippman, Scott M; Ruckdeschel, John; Khuri, Fadlo R

    2013-11-20

    Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 μg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

  19. Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial.

    Science.gov (United States)

    Kerem, Eitan; Konstan, Michael W; De Boeck, Kris; Accurso, Frank J; Sermet-Gaudelus, Isabelle; Wilschanski, Michael; Elborn, J Stuart; Melotti, Paola; Bronsveld, Inez; Fajac, Isabelle; Malfroot, Anne; Rosenbluth, Daniel B; Walker, Patricia A; McColley, Susanna A; Knoop, Christiane; Quattrucci, Serena; Rietschel, Ernst; Zeitlin, Pamela L; Barth, Jay; Elfring, Gary L; Welch, Ellen M; Branstrom, Arthur; Spiegel, Robert J; Peltz, Stuart W; Ajayi, Temitayo; Rowe, Steven M

    2014-07-01

    Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis in 10% of patients. This trial was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis. This randomised, double-blind, placebo-controlled, phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe. Eligible patients with nonsense-mutation cystic fibrosis (aged ≥ 6 years; abnormal nasal potential difference; sweat chloride >40 mmol/L; forced expiratory volume in 1 s [FEV1] ≥ 40% and ≤ 90%) were randomly assigned by interactive response technology to receive oral ataluren (10 mg/kg in morning, 10 mg/kg midday, and 20 mg/kg in evening) or matching placebo for 48 weeks. Randomisation used a block size of four, stratified by age, chronic inhaled antibiotic use, and percent-predicted FEV1. The primary endpoint was relative change in percent-predicted FEV1 from baseline to week 48, analysed in all patients with a post-baseline spirometry measurement. This study is registered with ClinicalTrials.gov, number NCT00803205. Between Sept 8, 2009, and Nov 30, 2010, 238 patients were randomly assigned, of whom 116 in each treatment group had a valid post-baseline spirometry measurement. Relative change from baseline in percent-predicted FEV1 did not differ significantly between ataluren and placebo at week 48 (-2.5% vs -5.5%; difference 3.0% [95% CI -0.8 to 6.3]; p=0.12). The number of pulmonary exacerbations did not differ significantly between treatment groups (rate ratio 0.77 [95% CI 0.57-1.05]; p=0.0992). However, post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5.7% difference (95% CI 1.5-10.1) in relative change from baseline in percent-predicted FEV1 between the ataluren and placebo groups at week 48 (-0.7% [-4.0 to 2.1] vs -6.4% [-9.8 to -3.7]; nominal p=0.0082), and fewer pulmonary

  20. 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

  1. Double blind placebo controlled exposure to molds

    DEFF Research Database (Denmark)

    Meyer, H W; Jensen, K A; Nielsen, K F

    2005-01-01

    with a positive histamine release test to Penicillium chrysogenum were exposed double- blinded to either placebo, approximately 600,000 spores/m3 air of P. chrysogenum or approximately 350,000 spores/m3 of Trichoderma harzianum for 6 min on three separate days. A statistically significant rise in symptoms from...... mucous membranes appeared from the 9-graded symptom scale after exposure to T. harzianum or placebo. Dichotomizing the data, whether the participants experienced at least a two-step rise on the symptom scale or not, gave borderline increase in mucous membrane symptoms after exposure to P. chrysogenum...... to placebo in eight sensitive school employees. However, a statistical type II error cannot be excluded because of the small sample size. PRACTICAL IMPLICATIONS: In this double blind, placebo controlled study of mold exposure changes in symptoms, objective measurements and blood samples were small and mostly...

  2. The efficacy and safety of a nicotine conjugate vaccine (NicVAX® or placebo co-administered with varenicline (Champix® for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Hoogsteder Philippe HJ

    2012-12-01

    Full Text Available Abstract Background A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix® and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design Two centers will include a total of 600 smokers who are motivated to quit smoking. At week −2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain

  3. First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy.

    Directory of Open Access Journals (Sweden)

    Peter A Anton

    Full Text Available Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.HIV-1 seronegative, sexually-abstinent men and women (N = 36 were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25% with placebo gel (1∶1∶1. Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.All 36 subjects enrolled completed the 7-14 week trial (100% retention including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm. There were 81 Grade 1 adverse events (AEs and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1(BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV

  4. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...... or placebo; and after a 12-month open phase of GH therapy. In the placebo group, insulin sensitivity and fat mass increased and lipid oxidation decreased, whereas glucose oxidation increased (p...

  5. Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis

    Directory of Open Access Journals (Sweden)

    Palacios Santiago

    2010-06-01

    Full Text Available Abstract Background We report the safety findings from a 3-year phase 3 study (NCT00205777 of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE reporting and routine physical, gynecologic, and breast examination. Results Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. Trial Registration Trial registration number: NCT00205777; Trial registration date: September 16, 2005

  6. A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: North Central Cancer Treatment group study N04CA.

    Science.gov (United States)

    Loprinzi, Charles L; Balcueva, Ernie P; Liu, Heshan; Sloan, Jeff A; Kottschade, Lisa A; Stella, Philip J; Carlson, Mark D; Moore, Dennis F; Zon, Robin T; Levitt, Ralph; Jaslowski, Anthony J

    2011-01-01

    Vaginal dryness is a common problem for which effective and safe nonestrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness, the current trial was conducted. A double-blind, placebo-controlled, randomized trial design was used to compare pilocarpine, at target doses of 5 mg twice daily and 5 mg four times daily, with a placebo. Vaginal dryness was recorded by patient-completed questionnaires at baseline and weekly for 6 weeks after study initiation. The primary endpoint for this study was the area under the curve summary statistic composed of the longitudinal responses obtained at baseline and through the 6 weeks of treatment to a numerical analogue scale asking patients to rate their perceived amount of vaginal dryness. The primary analysis was carried out by a single t test using a two-side alternative to compare the collective pilocarpine treatment arms with the collective placebo arms. A total of 201 patients enrolled in this trial. The primary analysis, comparing vaginal dryness symptoms in the collective pilocarpine arms against the placebo arm, did not reveal any benefit for the pilocarpine treatment. This finding was confirmed by other secondary analyses. Toxicity evaluation revealed more nausea, sweating, rigors, and urinary frequency with the pilocarpine arms compared with the placebo arm.

  7. Pilot study of aprepitant for prevention of post-ERCP pancreatitis in high risk patients: a phase II randomized, double-blind placebo controlled trial

    Science.gov (United States)

    Shah, Tilak; Liddle, Rodger A.; Branch, M. Stanley; Jowell, Paul; Obando, Jorge; Poleski, Martin H.

    2013-01-01

    Objectives Animal studies have demonstrated a role for substance P binding to neurokinin-1 receptor in the pathogenesis of acute pancreatitis. Our aim was to assess the efficacy of a neurokinin-1 receptor antagonist (aprepitant) at preventing post-ERCP pancreatitis in high risk patients. Methods Randomized, double-blind, placebo controlled trial at a single academic medical center. Patients at high risk for post-ERCP pancreatitis received either placebo or oral aprepitant administered 4 hours prior to ERCP, 80 mg 24 hours after the first dose, and then 80 mg 24 hours after the second dose. Fisher's exact test was used to compare incidence of post-ERCP pancreatitis in the two groups. Results 34 patients received aprepitant and 39 patients received placebo. Baseline characteristics were similar between the two groups. Incidence of acute pancreatitis was 7 in the aprepitant group and 7 in the placebo group. Hospitalization within 7 days post-procedure for abdominal pain that did not meet criteria for acute pancreatitis occurred in 6 and 9 patients in the aprepitant and placebo groups respectively (p=0.77). Conclusions Aprepitant did not lower incidence of post-ERCP pancreatitis in this preliminary human study. Larger studies potentially using the recently available intravenous formulation are necessary to conclusively clarify the efficacy of aprepitant in this setting. PMID:22964958

  8. Silodosin for men with chronic prostatitis/chronic pelvic pain syndrome: results of a phase II multicenter, double-blind, placebo controlled study.

    Science.gov (United States)

    Nickel, J Curtis; O'Leary, Michael P; Lepor, Herbert; Caramelli, Kim E; Thomas, Heather; Hill, Lawrence A; Hoel, Gary E

    2011-07-01

    We evaluated the efficacy and safety of 2 doses of silodosin vs placebo in men with moderate to severe abacterial chronic prostatitis/chronic pelvic pain syndrome who had not been treated previously with α-blockers for chronic prostatitis/chronic pelvic pain syndrome. In this multicenter, randomized, double-blind, phase II study, men 18 years old or older with chronic prostatitis/chronic pelvic pain syndrome, a total National Institutes of Health Chronic Prostatitis Symptom Index score of 15 or greater and a National Institutes of Health Chronic Prostatitis Symptom Index pain score of 8 or greater received 4 or 8 mg silodosin, or placebo once daily for 12 weeks. The primary efficacy end point was change from baseline to week 12 in National Institutes of Health Chronic Prostatitis Symptom Index total score. Of 151 patients (mean age 48 years) 52 received 4 mg silodosin, 45 received 8 mg silodosin and 54 received placebo. Silodosin 4 mg was associated with a significant decrease in total National Institutes of Health Chronic Prostatitis Symptom Index score (mean ± SD change -12.1 ± 9.3) vs placebo (-8.5 ± 7.2, p = 0.0224), including a decrease in urinary symptom (-2.2 ± 2.7, placebo -1.3 ± 3.0, p = 0.0102) and quality of life (-4.1 ± 3.1, placebo -2.7 ± 2.5, p = 0.0099) subscores. The 4 mg dose of silodosin also significantly increased Medical Outcomes Study Short Form 12 physical component scores (4.2 ± 8.1, placebo 1.7 ± 9.0, p = 0.0492). During global response assessment 56% of patients receiving 4 mg silodosin vs 29% receiving placebo reported moderate or marked improvement (p = 0.0069). Increasing the dose of silodosin to 8 mg resulted in no incremental treatment effects. Silodosin 4 mg relieved symptoms and improved quality of life in men with chronic prostatitis/chronic pelvic pain syndrome but its efficacy requires confirmation in additional studies. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier

  9. Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial.

    Science.gov (United States)

    Kaku, K; Enya, K; Nakaya, R; Ohira, T; Matsuno, R

    2015-07-01

    To assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise. This phase III, double-blind, placebo-controlled, multicentre study included 192 patients randomized to once-daily treatment with fasiglifam 25 mg (n = 63) or 50 mg (n = 62) or placebo (n = 67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24. At week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  10. Efficacy and safety of ceftriaxone for amyotrophic lateral sclerosis: results of a multi-stage, randomised, double-blind, placebo-controlled, phase 3 study

    Science.gov (United States)

    Cudkowicz, Merit E; Titus, Sarah; Kearney, Marianne; Yu, Hong; Sherman, Alexander; Schoenfeld, David; Hayden, Douglas; Shui, Amy; Brooks, Benjamin; Conwit, Robin; Felsenstein, Donna; Greenblatt, David J.; Keroack, Myles; Kissel, John T; Miller, Robert; Rosenfeld, Jeffrey; Rothstein, Jeffrey; Simpson, Ericka; Tolkoff-Rubin, Nina; Zinman, Lorne; Shefner, Jeremy M.

    2014-01-01

    Background Glutamate excitotoxicity may contribute to the pathophysiology of amyotrophic lateral sclerosis (ALS). Studies in ALS animal models show decreased excitatory amino acid transporter 2 (EAAT2) overexpression delays onset and prolongs survival, and that ceftriaxone increases EAAT2 activity in rodent brains. Phase 1, 2, and 3 clinical studies of ceftriaxone for ALS were combined into a three-stage, nonstop study. Methods 514 participants were randomised to ceftriaxone (n=341) or placebo (n=173); 66 participants were enrolled in stages 1 (pharmacokinetics) and 2 (safety) to determine cerebrospinal fluid and blood pharmacokinetics and safety of two dosages: 2 grams and 4 grams/day of ceftriaxone. All participants continued into stage 3 (efficacy) in blinded fashion with participants who began treatment on the discontinued dose analysed in the same group as those on the dose that that was continued. In stage 3, 44 participants previously assigned to 2 or 4 g ceftriaxone in stage 2 received 4 g ceftriaxone; 21 participants assigned to placebo in stage 2 continued on placebo. 448 new participants were randomized in stage 3 to 4 g ceftriaxone or placebo (2:1). Participants, family members and all site staff were blinded to treatment assignment. Computerized randomisation sequence using permuted blocks of 3 was stratified by riluzole use and blocked by site. Participants received 2g ceftriaxone or placebo BID via a central venous catheter (CVC) administered in the home setting by a trained caregiver. To minimize biliary side effects, participants assigned to ceftriaxone also received 300 mg ursodiol BID in a blinded manner; those assigned to placebo received matched placebo capsules BID. The co-primary efficacy outcomes were survival and functional decline, using the slope of scores on the ALS Functional Rating Scale-Revised (ALSFRS-R). The first participant entered the trial on September 4, 2006 (stage 1); the first stage-3 participant entered on June 4, 2009. The

  11. Placebo reactions in double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; van der Heide, S.; Bijleveld, C. M. A.; Kukler, J.; Duiverman, E. J.; Dubois, A. E. J.

    Background: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented. Objective: To analyse the occurrence and

  12. Placebo reactions in double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; van der Heide, S.; Bijleveld, C. M. A.; Kukler, J.; Duiverman, E. J.; Dubois, A. E. J.

    2007-01-01

    Background: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented. Objective: To analyse the occurrence and

  13. A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults.

    Directory of Open Access Journals (Sweden)

    Michael C Keefer

    Full Text Available BACKGROUND: We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35 vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN and env (Ad35-ENV, both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults. METHODS: Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively within one of four dosage groups: Ad35-GRIN/ENV 2×10(9 (A, 2×10(10 (B, 2×10(11 (C, or Ad35-GRIN 1×10(10 (D viral particles. RESULTS: No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A-D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC per 10(6 PBMC to any antigen was 78-139 across Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination. CONCLUSION/SIGNIFICANCE: Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second

  14. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study

    Science.gov (United States)

    Ravandi, Farhad; Ritchie, Ellen K.; Sayar, Hamid; Lancet, Jeffrey E.; Craig, Michael D.; Vey, Norbert; Strickland, Stephen A.; Schiller, Gary J.; Jabbour, Elias; Erba, Harry P.; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M.; Cortes, Jorge; Roboz, Gail J.; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L.; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R.; Fox, Judith A.; Ward, Renee; Smith, Jennifer A.; Acton, Gary; Mehta, Cyrus; Stuart, Robert K.; Kantarjian, Hagop M.

    2016-01-01

    Summary Background Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML. Methods VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m2 IV days 1,4) plus cytarabine (1 g/m2 IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801). Findings Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6·1 months with pla/cyt (hazard ratio 0·87; unstratified log-rank p=0·061; stratified p=0·0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6·7 and 5·3 months; p=0·0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30·1% vs 16·3%, p<0·0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7·9% vs 6·6%; 60-day, 19·7% vs 19·4%). Treatment-related deaths occurred at any time in 18 patients (5·1%) with vos/cyt and 8 (2·3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Interpretation Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML

  15. A phase 2, randomized, placebo-controlled, dose-ranging study of the calcium-sensing receptor antagonist MK-5442 in the treatment of postmenopausal women with osteoporosis.

    Science.gov (United States)

    Halse, Johan; Greenspan, Susan; Cosman, Felicia; Ellis, Graham; Santora, Arthur; Leung, Albert; Heyden, Norman; Samanta, Suvajit; Doleckyj, Steven; Rosenberg, Elizabeth; Denker, Andrew E

    2014-11-01

    MK-5442 is an orally bioavailable calcium-sensing receptor antagonist that is hypothesized to stimulate bone formation by stimulating endogenous secretion of a pulse of PTH. Earlier clinical and preclinical studies demonstrated increased bone mineral density (BMD) after treatment. Our objective was to identify a dose of MK-5442 that produces osteoanabolic effects without excessive hypercalcemia. This was a randomized, double-blind, placebo-controlled, parallel-group trial of private or institutional practice. In total, 383 postmenopausal women with osteoporosis were administered daily oral MK-5442 (2.5, 5, 7.5, 10, or 15 mg) or placebo. Serum PTH and calcium, bone turnover markers, areal BMD, and safety were evaluated. A dose-dependent transient increase in PTH occurred after an MK-5442 dose and lasted more than 3.5 hours. Compared with placebo, significant increases in bone formation markers (serum procollagen 1 N-terminal peptide and bone-specific alkaline phosphatase) were observed by 6 months, whereas bone resorption markers (serum C-telopeptide of type 1 collagen, urine N-telopeptides of type 1 collagen) initially decreased but were also significantly increased by 6 months. Despite the biochemical marker changes suggestive of an anabolic response, there were no statistically significant differences between any dose of MK-5442 and placebo in percent change from baseline at month 6 in any of the BMD endpoints. The frequency of hypercalcemia (trough serum calcium ≥ 10.8 mg/dL) was greater with higher MK-5442 doses. In postmenopausal women with low bone mass, treatment with MK-5442 resulted in transient pulses of PTH. Bone formation markers increased quickly and bone resorption markers decreased temporarily, suggestive of an anabolic window. However, there were no increases in BMD versus placebo.

  16. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Hartemann, Agnès; Bensimon, Gilbert; Payan, Christine A; Jacqueminet, Sophie; Bourron, Olivier; Nicolas, Nathalie; Fonfrede, Michèle; Rosenzwajg, Michelle; Bernard, Claude; Klatzmann, David

    2013-12-01

    An improper balance of regulatory/effector T (Treg/Teff) cells is central to the development of autoimmune diseases, including type 1 diabetes. We previously showed that low-dose interleukin 2 (IL2) induced Treg cell expansion and activation and clinical improvement in patients with hepatitis-C-virus-induced vasculitis. We aimed to establish which low doses of IL2 would be safe and induce Treg cells in patients with type 1 diabetes, considering that: (1) type 1 diabetes might be linked to alteration of the IL2/IL2R activation pathway; (2) activation of pathogenic Teff cells by IL2 could exacerbate disease; and (3) the safety of low-dose IL2 is not known in type 1 diabetes. This was a single-centre phase 1/2 study. 24 adult patients (18-55 years) with established insulin-dependent type 1 diabetes and at least one diabetes-related autoantibody were enrolled and randomly assigned (in a 1:1:1:1 ratio, by computer-generated randomisation list, with block size four) to placebo or IL2 at 0.33 MIU/day, 1 MIU/day, or 3 MIU/day for a 5-day course and were followed up for 60 days. All investigators and participants were masked to assignment. The primary outcome was change in Treg cells, measured by flow cytometry, and expressed as a percentage of CD4+ T cells, from day 1 to day 60. This trial is registered with ClinicalTrials.gov, number NCT01353833. Six patients were assigned to each group between June 1, 2011, and Feb 3, 2012. IL2 was well tolerated at all doses, with no serious adverse events. However, there was a dose-response association for non-serious adverse events during the treatment phase (days 1-6); one patient in the placebo group, three patients in the 0.33 MIU group, five patients in the 1 MIU group, and six patients in the 3 MIU group had non-serious adverse events. The most common adverse events in the treatment phase were injection-site reaction (no patients with placebo vs three patients with 0.33 MIU and 1 MIU vs two patients with 3 MIU) and influenza

  17. A randomized, double-blind, placebo-controlled phase 2 study of α4β2 agonist ABT-894 in adults with ADHD.

    Science.gov (United States)

    Bain, Earle E; Robieson, Weining; Pritchett, Yili; Garimella, Tushar; Abi-Saab, Walid; Apostol, George; McGough, James J; Saltarelli, Mario D

    2013-02-01

    Dysregulation of the neuronal nicotinic acetylcholine receptor (NNR) system has been implicated in attention-deficit/hyperactivity disorder (ADHD), and nicotinic agonists improve attention across preclinical species and humans. Hence, a randomized, double-blind, placebo-controlled, crossover study was designed to determine the safety and efficacy of a novel α4β2 NNR agonist (ABT-894 (3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane)) in adults with ADHD. Participants (N=243) were randomized to one of four dose regimens of ABT-894 (1, 2, and 4 mg once daily (QD)) or 4 mg twice daily (BID) or the active comparator atomoxetine (40 mg BID) vs placebo for 28 days. Following a 2-week washout period, participants crossed over to the alternative treatment condition (active or placebo) for an additional 28 days. Primary efficacy was based on an investigator-rated Conners' Adult ADHD Rating Scale (CAARS:Inv) Total score at the end of each 4-week treatment period. Additional secondary outcome measures were assessed. A total of 238 patients were assessed for safety end points, 236 patients were included in the intent-to-treat data set, and 196 were included in the completers data set, which was the prespecified, primary data set for efficacy. Both the 4 mg BID ABT-894 and atomoxetine groups demonstrated significant improvement on the primary outcome compared with placebo. Several secondary outcome measures were also significantly improved with 4 mg BID ABT-894. Overall, ABT-894 was well tolerated at all dose levels. These results provide initial proof of concept for the use of α4β2 agonists in the treatment of adults with ADHD. Further investigation of ABT-894, including higher doses, is therefore warranted.

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

    Science.gov (United States)

    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

    Background. Urinary tract infections (UTIs) are common among women and frequently recur. Depletion of vaginal lactobacilli is associated with UTI risk, which suggests that repletion may be beneficial. We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) for prevention of recurrent UTI in premenopausal women. Methods. One hundred young women with a history of recurrent UTI received antimicrobials for acute UTI and then were randomized to receive either Lactin-V or placebo daily for 5 d, then once weekly for 10 weeks. Participants were followed up at 1 week and 10 weeks after intervention and for UTIs; urine samples for culture and vaginal swabs for real-time quantitative 16S ribosomal RNA gene polymerase chain reaction for L. crispatus were collected. Results. Recurrent UTI occurred in 7/48 15% of women receiving Lactin-V compared with 13/48 27% of women receiving placebo (relative risk [RR], .5; 95% confidence interval, .2–1.2). High-level vaginal colonization with L. crispatus (≥106 16S RNA gene copies per swab) throughout follow-up was associated with a significant reduction in recurrent UTI only for Lactin-V (RR for Lactin-V, .07; RR for placebo, 1.1; P < .01). Conclusions. Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI. Larger efficacy trials of this novel preventive method for recurrent UTI are warranted. Clinical Trials Registration. NCT00305227. PMID:21498386

  19. Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia

    Science.gov (United States)

    2013-01-01

    Background Trigeminal neuralgia (TN) is a rare severe unilateral facial pain condition. Current guidelines in trigeminal neuralgia management recommend sodium channel blockers – carbamazepine or oxcarbazepine – as the first-line treatment. However, the currently available drugs are often associated with poor tolerability resulting in sub-optimal pain control. CNV1014802 is a novel sodium channel blocker that is being assessed in the treatment of trigeminal neuralgia. Due to the severity of the condition, it is not ethical to conduct a traditional placebo-controlled randomized controlled trial. It is also difficult to use an active control such as carbamazepine, the current gold standard, because of its complex pharmacology and potential for drug interactions. Methods/Design The trial uses a randomized withdrawal design to assess efficacy in this rare condition. There is a 21-day open-label phase followed by a randomized 28-day placebo-controlled phase for responders. Thirty patients will be randomized. The primary outcome measure will be pain relief, but secondary measures of quality of life will be of significant importance given the effect of this condition on activities of daily living. Safety and adverse event endpoints are described. Discussion There have been very few well-controlled, randomized, placebo-controlled studies in trigeminal neuralgia, and the majority of drugs have had other primary uses. Due to the severity of the pain, minimizing the time a patient is administered placebo was a key factor in designing this study. This study will not only provide data on the efficacy of CNV1014802 in trigeminal neuralgia, but will also provide information on the effectiveness and acceptability of a novel trial design in trigeminal neuralgia. Trial registration Trial number NCT01540630 PMID:24267010

  20. Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial.

    Science.gov (United States)

    Hovingh, G Kees; Kastelein, John J P; van Deventer, Sander J H; Round, Patrick; Ford, John; Saleheen, Danish; Rader, Daniel J; Brewer, H Bryan; Barter, Philip J

    2015-08-01

    Dyslipidaemia remains a significant risk factor for cardiovascular disease and additional lipid-modifying treatments are warranted to further decrease the cardiovascular disease burden. We assessed the safety, tolerability and efficacy of a novel cholesterol esterase transfer protein (CETP) inhibitor TA-8995 in patients with mild dyslipidaemia. In this randomised, double-blind, placebo-controlled, parallel-group phase 2 trial, we recruited patients (aged 18-75 years) from 17 sites (hospitals and independent clinical research organisations) in the Netherlands and Denmark with fasting LDL cholesterol levels between 2·5 mmol/L and 4·5 mmol/L, HDL cholesterol levels between 0·8 and 1·8 mmol/L and triglyceride levels below 4·5 mmol/L after washout of lipid-lowering treatments. Patients were randomly allocated (1:1) by a computer-generated randomisation schedule to receive one of the following nine treatments: a once a day dose of 1 mg, 2·5 mg, 5 mg, or 10 mg TA-8995 or matching placebo; 10 mg TA-8995 plus 20 mg atorvastatin; 10 mg TA-8995 plus 10 mg rosuvastatin or 20 mg atorvastatin or 10 mg rosuvastatin alone. We overencapsulated statins to achieve masking. The primary outcome was percentage change in LDL cholesterol and HDL cholesterol from baseline at week 12, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01970215. Between Aug 15, 2013, and Jan 10, 2014, 364 patients were enrolled. At week 12, LDL cholesterol levels were reduced by 27·4% in patients assigned to the 1 mg dose, 32·7% in patients given the 2·5 mg dose, 45·3% in those given the 5 mg dose, and 45·3% in those given the 10 mg dose (p<0·0001). LDL cholesterol levels were reduced by 68·2% in patients given 10 mg TA-8995 plus atorvastatin, and by 63·3% in patients given rosuvastatin plus 10 mg TA-8995 (p<0·0001). A daily dose of 1 mg TA-8995 increased HDL cholesterol levels by 75·8%, 2·5 mg by 124·3%, 5 mg by 157·1%, and 10 mg dose by 179·0% (p

  1. Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial.

    Science.gov (United States)

    Huttner, Angela; Hatz, Christoph; van den Dobbelsteen, Germie; Abbanat, Darren; Hornacek, Alena; Frölich, Rahel; Dreyer, Anita M; Martin, Patricia; Davies, Todd; Fae, Kellen; van den Nieuwenhof, Ingrid; Thoelen, Stefan; de Vallière, Serge; Kuhn, Anette; Bernasconi, Enos; Viereck, Volker; Kavvadias, Tilemachos; Kling, Kerstin; Ryu, Gloria; Hülder, Tanja; Gröger, Sabine; Scheiner, David; Alaimo, Cristina; Harbarth, Stephan; Poolman, Jan; Fonck, Veronica Gambillara

    2017-05-01

    Escherichia coli infections are increasing worldwide in community and hospital settings. The E coli O-antigen is a promising vaccine target. We aimed to assess the safety and immunogenicity of a bioconjugate vaccine containing the O-antigens of four E coli serotypes (ExPEC4V). In this multicentre phase 1b, first-in-human, single-blind, placebo-controlled trial, we randomly assigned (1:1) healthy adult women with a history of recurrent urinary tract infection (UTI) to receive a single injection of either intramuscular ExPEC4V or placebo. The primary outcome was the incidence of adverse events among vaccine and placebo recipients throughout the study. Secondary outcomes included immunogenicity and antibody functionality, and the incidence of UTIs caused by E coli vaccine serotypes in each group. This study is registered with ClinicalTrials.gov, number NCT02289794. Between Jan 20, 2014, and Aug 27, 2014, 93 women received target-dose ExPEC4V and 95 received placebo. The vaccine was well tolerated: no vaccine-related serious adverse events occurred. Overall, 56 (60%) target-dose vaccines and 47 (49%) placebo recipients experienced at least one adverse event that was possibly, probably, or certainly related to injection. Vaccination induced significant IgG responses for all serotypes: at day 30 compared with baseline, O1A titres were 4·6 times higher, O2 titres were 9·4 times higher, O6A titres were 4·9 times higher, and O25B titres were 5·9 times higher (overall pcoli was noted in the vaccine compared with the placebo group (0·149 mean episodes vs 0·146 mean episodes; p=0·522). In post-hoc exploratory analyses of UTIs with higher bacterial counts (≥10(5) colony-forming units per mL), the number of vaccine serotype UTIs did not differ significantly between groups (0·046 mean episodes in the vaccine group vs 0·110 mean episodes in the placebo group; p=0·074). However, significantly fewer UTIs caused by E coli of any serotype were noted in the vaccine group

  2. Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane's efficacy and safety in the treatment of CIN: implications for cervical cancer prevention.

    Science.gov (United States)

    Ashrafian, Levon; Sukhikh, Gennady; Kiselev, Vsevolod; Paltsev, Mikhail; Drukh, Vadim; Kuznetsov, Igor; Muyzhnek, Ekaterina; Apolikhina, Inna; Andrianova, Evgeniya

    2015-01-01

    The article presents the results of a clinical trial on the efficacy and safety of a novel pharmaceutical composition in the form of vaginal suppositories containing diindolylmethane in the course of cervical intraepithelial neoplasia (CIN) I-II conservative treatment. It offers an attractive drug therapy for more personalized prevention of cervical cancer. A total of 78 women of reproductive age were included. This was a multicenter, randomized, placebo-controlled, double-blind, parallel-group trial with efficacy determined by histological evaluation of cervical biopsies. The efficacy of active drug treatment (100 and 200 mg/day) in both treatment groups was significantly higher in comparison with the placebo group, according to the primary efficacy end point (proportion of patients with complete CIN regression after 90-180 days of the study drug treatment). The efficacies were 100.0 % (confidence interval (CI) 95 %: 82.35-100.00 %), 90.5 % (CI 95 %: 69.62-98.83 %), and 61.1 % (CI 95 %: 35.75-82.70 %), for the high dose, low does, and placebo, respectively. Adverse events in the placebo group were reported in 22 % of patients (CI 95 %: 7.5-43.7 %); in the first treatment group (100 mg/day), adverse events were reported in 40.0 % of patients (CI 95 %: 21.1-61.3 %); in the second treatment group (200 mg/day), adverse events were reported in 42.0 % of patients (CI 95 %: 22.1-63.4 %). The differences in side effects between treatment groups treated with the active drug and placebo were statistically significant. No serious adverse events were reported in any of the groups. Thus, the use of diindolylmethane in the form of intravaginal suppositories can be effective in patients with CIN I-II and is not accompanied by clinically significant side effects. This approach could be a better option for young women with CIN I-II as it takes in attention their reproductive plans. ID: ChiCTR-INR-15007497 (2 December 2015).

  3. Efficacy and safety of bilastine in Japanese patients with chronic spontaneous urticaria: A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II/III study.

    Science.gov (United States)

    Hide, Michihiro; Yagami, Akiko; Togawa, Michinori; Saito, Akihiro; Furue, Masutaka

    2017-04-01

    Bilastine, a novel non-sedating second-generation H1-antihistamine, has been widely used in the treatment of allergic rhinoconjunctivitis and urticaria with a recommended dose of 20 mg once daily in most European countries since 2010. We evaluated its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU). We conducted a multicenter, randomized, double-blind, placebo-controlled phase II/III study (trial registration No. JapicCTI-142574). Patients (age, 18-74 years) were randomly assigned to receive bilastine 20 mg, 10 mg or placebo once daily for 2 weeks. The primary efficacy endpoint was the change from baseline (Day -3 to 0) in total symptom score (TSS) at 2 weeks (Day 8-14), consisting of the itch and rash scores. A total of 304 patients were randomly allocated to bilastine 20 mg (101 patients), bilastine 10 mg (100 patients), and placebo (103 patients). The changes in TSS at 2 weeks were significantly decreased by bilastine 20 mg than did placebo (p < 0.001), demonstrating the superiority of bilastine 20 mg. Bilastine 10 mg also showed a significant difference from placebo (p < 0.001). The TSS changes for the bilastine showed significant improvement from Day 1, and were maintained during the treatment period. The Dermatology Life Quality Index scores were also improved in bilastine than in placebo. The bilastine treatments were safe and well tolerated. Two-week treatment with bilastine (20 or 10 mg) once daily was effective and tolerable in Japanese patients with CSU, demonstrating an early onset of action. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  4. Safety and Efficacy of Tien-Hsien Liquid Practical in Patients with Refractory Metastatic Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase IIa Trial

    Directory of Open Access Journals (Sweden)

    Wen-Hung Kuo

    2012-01-01

    Full Text Available To evaluate the safety and efficacy of Tien-Hsien Liquid Practical (THL-P, a Chinese herbal mixture, in patients with refractory metastatic breast cancer, we performed a randomized, double-blind, placebo-controlled, parallel-group, phase IIa pilot trial. Patients were randomly assigned to either receive THL-P or matching placebo and followed up every 4 weeks for 24 weeks. The primary endpoint was changes in the global health status/quality of life (GHS/QOL scale. The secondary endpoints were changes in functional and symptom scales, immunomodulating effects, and adverse events. Sixty-three patients were enrolled between June 2009 and June 2011. The intent-to-treat population included 28 patients in the THL-P group and 11 patients in the placebo group. Compared to the placebo group, the THL-P group had significant improvement from baseline to last visit in GHS/QOL (41.7 versus −33.3; P<0.05, CD3, CD4/CD8, CD19, CD16+56 positive cells (P<0.05, and higher levels of physical, role, emotional, and cognitive functioning, as well as decreased fatigue and systemic side effects. Treatment-related adverse events were mild constipation and localized itching, and no serious adverse events were reported. THL-P appears to be a safe alternative adjuvant treatment for patients with refractory metastatic breast cancer, as it effectively improves QOL and palliates cancer-related symptoms.

  5. Symptomatic treatment with lanreotide microparticles in inoperable bowel obstruction resulting from peritoneal carcinomatosis: a randomized, double-blind, placebo-controlled phase III study.

    Science.gov (United States)

    Mariani, Pascale; Blumberg, Joëlle; Landau, Alain; Lebrun-Jezekova, Daniela; Botton, Estelle; Beatrix, Olivier; Mayeur, Didier; Herve, Robert; Maisonobe, Pascal; Chauvenet, Laure

    2012-12-10

    To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P < .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P < .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.

  6. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis.

    Science.gov (United States)

    Sansone, Valeria A; Burge, James; McDermott, Michael P; Smith, Patty C; Herr, Barbara; Tawil, Rabi; Pandya, Shree; Kissel, John; Ciafaloni, Emma; Shieh, Perry; Ralph, Jeffrey W; Amato, Antony; Cannon, Steve C; Trivedi, Jaya; Barohn, Richard; Crum, Brian; Mitsumoto, Hiroshi; Pestronk, Alan; Meola, Giovanni; Conwit, Robin; Hanna, Michael G; Griggs, Robert C

    2016-04-12

    To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP. © 2016 American Academy of Neurology.

  7. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis

    Science.gov (United States)

    Burge, James; McDermott, Michael P.; Smith, Patty C.; Herr, Barbara; Tawil, Rabi; Pandya, Shree; Kissel, John; Ciafaloni, Emma; Shieh, Perry; Ralph, Jeffrey W.; Amato, Antony; Cannon, Steve C.; Trivedi, Jaya; Barohn, Richard; Crum, Brian; Mitsumoto, Hiroshi; Pestronk, Alan; Meola, Giovanni; Conwit, Robin; Hanna, Michael G.; Griggs, Robert C.

    2016-01-01

    Objective: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. Methods: Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. Results: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form–36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). Conclusions: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. Classification of evidence: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP. PMID:26865514

  8. Theophylline as an add-on to thrombolytic therapy in acute ischaemic stroke (TEA-Stroke): A randomized, double-blinded, placebo-controlled, two-centre phase II study

    DEFF Research Database (Denmark)

    Modrau, Boris; Hjort, Niels; Østergaard, Leif;

    2016-01-01

    the collateral supply in acute ischaemic brain tissue and thus facilitate reperfusion despite proximal vessel occlusion. The primary study objective is to evaluate whether theophylline is safe and efficient in acute ischaemic stroke patients as an add-on to thrombolytic therapy.MethodsThe TEA-Stroke Trial...... is a two-centre, proof of concept phase II clinical study with a randomized, double-blinded, placebo-controlled design. One hundred and twenty patients with acute ischaemic stroke and significant perfusion?diffusion mismatch, as determined by magnetic resonance imaging, are randomized 1:1 to either...... theophylline or placebo as an add-on to standard thrombolytic therapy.Study outcomeThe dual primary outcome measures include penumbra salvage (penumbral tissue not developing into infarcted tissue) and clinical improvement at the 24-h follow-up.DiscussionResults from studies of theophylline in stroke animal...

  9. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab.

    Science.gov (United States)

    Stroes, Erik; Colquhoun, David; Sullivan, David; Civeira, Fernando; Rosenson, Robert S; Watts, Gerald F; Bruckert, Eric; Cho, Leslie; Dent, Ricardo; Knusel, Beat; Xue, Allen; Scott, Rob; Wasserman, Scott M; Rocco, Michael

    2014-06-17

    This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses. Statin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients. The GAUSS-2 (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects) trial was a 12-week, double-blind study of randomized patients (2:2:1:1) to evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) both with daily oral placebo or subcutaneous placebo Q2W or QM both with daily oral ezetimibe 10 mg. Co-primary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12, and at week 12. Three hundred seven patients (age 62 ± 10 years; LDL-C 193 ± 59 mg/dl) were randomized. Evolocumab reduced LDL-C from baseline by 53% to 56%, corresponding to treatment differences versus ezetimibe of 37% to 39% (p <0.001). Muscle adverse events occurred in 12% of evolocumab-treated patients and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups. Robust efficacy combined with favorable tolerability makes evolocumab a promising therapy for addressing the largely unmet clinical need in high-risk patients with elevated cholesterol who are statin intolerant. (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2; NCT01763905). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication

    DEFF Research Database (Denmark)

    Tönnesen, K H; Albuquerque, P; Baitsch, G;

    1993-01-01

    The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized ...

  11. A phase II randomised double-blind placebo-controlled clinical trial investigating the efficacy and safety of ProstateEZE Max: a herbal medicine preparation for the management of symptoms of benign prostatic hypertrophy.

    Science.gov (United States)

    Coulson, Samantha; Rao, Amanda; Beck, Shoshannah L; Steels, Elizabeth; Gramotnev, Helen; Vitetta, Luis

    2013-06-01

    The aim of the clinical trial was to evaluate the efficacy and safety of ProstateEZE Max, an orally dosed herbal preparation containing Cucurbita pepo, Epilobium parviflorum, lycopene, Pygeum africanum and Serenoa repens in the management of symptoms of medically diagnosed benign prostate hypertrophy (BPH). This was a short-term phase II randomized double-blind placebo controlled clinical trial. The trial was conducted on 57 otherwise healthy males aged 40-80 years that presented with medically diagnosed BPH. The trial participants were assigned to receive 3 months of treatment (1 capsule per day) with either the herbal preparation (n = 32) or a matched placebo capsule (n = 25). The primary outcome measure was the international prostate specific score (IPSS) measured at baseline, 1, 2 and 3 months. The secondary outcomes were the specific questions of the IPSS and day-time and night-time urinary frequency. There was a significant reduction in IPSS total median score in the active group of 36% as compared to 8% for the placebo group, during the 3-months intervention (p < 0.05). The day-time urinary frequency in the active group also showed a significant reduction over the 3-months intervention (7.0-5.9 times per day, a reduction of 15.6% compared to no significant reduction change for the placebo group (6.2-6.3 times per day) (p < 0.03). The night-time urinary frequency was also significantly reduced in the active group (2.9-1.8, 39.3% compared to placebo (2.8-2.6 times, 7%) (p < 0.004). The herbal preparation (ProstateEZE Max) was shown to be well tolerated and have a significant positive effect on physical symptoms of BPH when taken over 3 months, a clinically significant outcome in otherwise healthy men. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. A Pooled Analysis Evaluating Renal Safety in Placebo- and Active Comparator-Controlled Phase III Trials of Multiple-Dose Injectable HPβCD-Diclofenac in Subjects with Acute Postoperative Pain.

    Science.gov (United States)

    Daniels, Stephen E; Gan, Tong J Tj; Hamilton, Douglas A; Singla, Neil; Lacouture, Peter G; Johnson, Olufunmibi; Min, Lauren H; Reyes, Christian R D; Carr, Daniel B

    2016-12-01

    OBJECTIVE : While injectable nonsteroidal anti-inflammatory drugs (NSAIDs) are a key component of postoperative multimodal analgesia, renal safety concerns may limit use in some patients. This study examined the renal safety of injectable HPβCD-diclofenac when given for ≤ 5 days following orthopedic or abdominal/pelvic surgery. METHODS : Pooled analysis of data from two randomized, placebo- and active comparator-controlled phase III trials in 608 total patients was conducted. Renal safety was assessed by examining treatment-emergent adverse events (AEs) and postoperative blood urea nitrogen (BUN) and serum creatinine shifts. RESULTS : There were three renal AEs each in the HPβCD-diclofenac (n = 318 patients) and placebo (n = 148 patients) groups, and two renal AEs in the ketorolac group (n = 142 patients). No significant difference in renal AE risk was detected for patients receiving HPβCD-diclofenac (RR: 1.40 [0.15,13.3]; P = 0.75) or ketorolac (RR: 2.08 [0.19,22.7]; P = 0.56) versus placebo. All renal AEs were mild or moderate in severity, and a single renal AE (acute renal failure in a patient receiving HPβCD-diclofenac) was treatment-related. One incidence of postoperative shift to high (> upper limit of normal) serum creatinine occurred in the HPβCD-diclofenac group (n = 2 in the ketorolac group). Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPβCD-diclofenac and placebo. CONCLUSIONS : While this analysis examined relatively brief exposure typical for parenterally administered analgesics in the postoperative setting in patients with largely normal renal function, the results suggest that HPβCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population.

  13. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial.

    Science.gov (United States)

    Dalton, James T; Barnette, Kester G; Bohl, Casey E; Hancock, Michael L; Rodriguez, Domingo; Dodson, Shontelle T; Morton, Ronald A; Steiner, Mitchell S

    2011-09-01

    BACKGROUND: Cachexia, also known as muscle wasting, is a complex metabolic condition characterized by loss of skeletal muscle and a decline in physical function. Muscle wasting is associated with cancer, sarcopenia, chronic obstructive pulmonary disease, end-stage renal disease, and other chronic conditions and results in significant morbidity and mortality. GTx-024 (enobosarm) is a nonsteroidal selective androgen receptor modulator (SARM) that has tissue-selective anabolic effects in muscle and bone, while sparing other androgenic tissue related to hair growth in women and prostate effects in men. GTx-024 has demonstrated promising pharmacologic effects in preclinical studies and favorable safety and pharmacokinetic profiles in phase I investigation. METHODS: A 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate GTx-024 in 120 healthy elderly men (>60 years of age) and postmenopausal women. The primary endpoint was total lean body mass assessed by dual energy X-ray absorptiometry, and secondary endpoints included physical function, body weight, insulin resistance, and safety. RESULTS: GTx-024 treatment resulted in dose-dependent increases in total lean body mass that were statistically significant (P < 0.001, 3 mg vs. placebo) and clinically meaningful. There were also significant improvements in physical function (P = 0.013, 3 mg vs. placebo) and insulin resistance (P = 0.013, 3 mg vs. placebo). The incidence of adverse events was similar between treatment groups. CONCLUSION: GTx-024 showed a dose-dependent improvement in total lean body mass and physical function and was well tolerated. GTx-024 may be useful in the prevention and/or treatment of muscle wasting associated with cancer and other chronic diseases.

  14. Evaluation of the Efficacy and Safety of Vonoprazan in Patients with Nonerosive Gastroesophageal Reflux Disease: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

    Directory of Open Access Journals (Sweden)

    Yoshikazu Kinoshita, MD, PhD

    2016-01-01

    Conclusions: Vonoprazan at doses of 10 mg and 20 mg are not superior to placebo with respect to proportion of days without heartburn, whereas the mean severity of heartburn is lower with vonoprazan compared with placebo in patients with NERD. ClinicalTrials.gov identifier: NCT01474369.

  15. A Phase IIIb, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of dexmedetomidine for sedation during awake fiberoptic intubation.

    Science.gov (United States)

    Bergese, Sergio D; Candiotti, Keith A; Bokesch, Paula M; Zura, Andrew; Wisemandle, Wayne; Bekker, Alex Y

    2010-01-01

    GABA-mediated sedatives have respiratory depressant properties that may be detrimental in patients with difficult airways. In this randomized, double-blind, multicenter, Phase IIIb Food and Drug Administration study, safety and efficacy of dexmedetomidine compared with placebo were evaluated as the primary sedative for awake fiberoptic intubation (AFOI). Patients were randomized to receive dexmedetomidine or saline. Patients were sedated with dexmedetomidine or rescue midazolam to achieve targeted sedation (Ramsay Sedation Scale ≥ 2) before topicalization and throughout AFOI. Primary efficacy endpoint was percentage of patients requiring rescue midazolam; secondary efficacy endpoints were total dose of rescue midazolam, percentage requiring additional rescue nonmidazolam medications, anesthesiologist's assessment of ease of subject care, and patient recall and satisfaction 24 hours postoperatively. Less rescue midazolam was required to maintain Ramsay Sedation Scale ≥2 (47.3% vs. 86.0%, P sedated with midazolam. Patients and anesthesiologists showed favorable satisfaction responses in both groups. Adverse events and patient recall were similar in both groups. Dexmedetomidine is effective as the primary sedative in patients undergoing AFOI. Some patients may require small supplemental doses of midazolam, in addition to dexmedetomidine, to achieve sufficient sedation for AFOI. Dexmedetomidine provides another AFOI option for sedation of patients with difficult airways.

  16. Recombinant T-Cell Receptor Ligand (RTL for Treatment of Multiple Sclerosis: A Double-Blind, Placebo-Controlled, Phase 1, Dose-Escalation Study

    Directory of Open Access Journals (Sweden)

    Vijayshree Yadav

    2012-01-01

    Full Text Available Background. Recombinant T-cell receptor ligand 1000 (RTL1000 is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG- 35–55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE in DR2 transgenic, C57BL/6, and SJL/J mice. Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS subjects. Methods. This was a multicenter, Phase I dose-escalation study in HLA-DR2+ MS subjects. Consecutive cohorts received RTL1000 doses of 2, 6, 20, 60, 200, and 100 mg, respectively. Subjects within each cohort randomly received a single intravenous infusion of RTL1000 or placebo at a 4 : 2 ratio. Safety monitoring included clinical, laboratory, and brain magnetic resonance imaging (MRI evaluations. Results. Thirty-four subjects completed the protocol. All subjects tolerated the 2–60 mg doses of RTL1000. Doses ≥100 mg caused hypotension and diarrhea in 3 of 4 subjects, leading to discontinuation of further enrollment. Conclusions. The maximum tolerated dose of RTL1000 in MS subjects is 60 mg, comparable to effective RTL doses in EAE. RTL1000 is a novel approach for MS treatment that may induce immunoregulation without immunosuppression and promote neural repair.

  17. Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects.

    Science.gov (United States)

    Kitamura, Masahiro; Akamatsu, Motoki; Kawanami, Masamitsu; Furuichi, Yasushi; Fujii, Takeo; Mori, Mari; Kunimatsu, Kazushi; Shimauchi, Hidetoshi; Ogata, Yorimasa; Yamamoto, Matsuo; Nakagawa, Taneaki; Sato, Shuichi; Ito, Koichi; Ogasawara, Takefumi; Izumi, Yuichi; Gomi, Kazuhiro; Yamazaki, Kazuhisa; Yoshie, Hiromasa; Fukuda, Mitsuo; Noguchi, Toshihide; Takashiba, Shogo; Kurihara, Hidemi; Nagata, Toshihiko; Hamachi, Takafumi; Maeda, Katsumasa; Yokota, Makoto; Sakagami, Ryuji; Hara, Yoshitaka; Noguchi, Kazuyuki; Furuuchi, Toshi; Sasano, Takashi; Imai, Enyu; Ohmae, Masatoshi; Koizumi, Hayuru; Watanuki, Mitsuru; Murakami, Shinya

    2016-04-01

    We investigated the efficacy, safety, and clinical significance of trafermin, a recombinant human fibroblast growth factor (rhFGF)-2, for periodontal regeneration in intrabony defects in Phase III trials. Study A, a multicenter, randomized, double-blind, placebo-controlled study, was conducted at 24 centers. Patients with periodontitis with 4-mm and 3-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 328 patients were randomly assigned (2:1) to receive 0.3% rhFGF-2 or placebo, and 323 patients received the assigned investigational drug during flap surgery. One of the co-primary endpoints, the percentage of bone fill at 36 weeks after drug administration, was significantly greater in the rhFGF-2 group at 37.131% (95% confidence interval [CI], 32.7502 to 41.5123; n = 208) than it was in the placebo group at 21.579% (95% CI, 16.3571 to 26.8011; n = 100; p < 0.001). The other endpoint, the clinical attachment level regained at 36 weeks, was not significantly different between groups. Study B, a multicenter, randomized, blinded (patients and evaluators of radiographs), and active-controlled study was conducted at 15 centers to clarify the clinical significance of rhFGF-2. Patients with 6-mm and 4-mm or deeper probing pocket depth and intrabony defects, respectively, were included. A total of 274 patients were randomly assigned (5:5:2) to receive rhFGF-2, enamel matrix derivative (EMD), or flap surgery alone. A total of 267 patients received the assigned treatment during flap surgery. The primary endpoint, the linear alveolar bone growth at 36 weeks, was 1.927 mm (95% CI, 1.6615 to 2.1920; n = 108) in the rhFGF-2 group and 1.359 mm (95% CI, 1.0683 to 1.6495; n = 109) in the EMD group, showing non-inferiority (a prespecified margin of 0.3 mm) and superiority of rhFGF-2 to EMD. Safety problems were not identified in either study. Therefore, trafermin is an effective and safe treatment for periodontal regeneration in intrabony

  18. Phase IIa, randomized placebo-controlled trial of single high dose cholecalciferol (vitamin D3) and daily Genistein (G-2535) versus double placebo in men with early stage prostate cancer undergoing prostatectomy

    Science.gov (United States)

    Jarrard, David; Konety, Badrinath; Huang, Wei; Downs, Tracy; Kolesar, Jill; Kim, Kyung Mann; Havighurst, Tom; Slaton, Joel; House, Margaret G; Parnes, Howard L; Bailey, Howard H

    2016-01-01

    Introduction and objectives: Prostate cancer (PCa) represents an important target for chemoprevention given its prolonged natural history and high prevalence. Epidemiologic and laboratory data suggest that vitamin D and genistein (soy isoflavone) may decrease PCa progression. The effect of vitamin D on prostate epithelial cell proliferation and differentiation is well documented and genistein may augment this affect through inhibition of the CYP24 enzyme, which is responsible for intracellular vitamin D metabolism. In addition, both genistein and vitamin D inhibit the intraprostatic synthesis of prostaglandin E2, an important mediator of inflammation. The objectives of this prospective multicenter trial were to compare prostate tissue calcitriol levels and down-stream related biomarkers in men with localized prostate cancer randomized to receive cholecalciferol and genistein versus placebo cholecalciferol and placebo genistein during the pre-prostatectomy period. Methods: Men undergoing radical prostatectomy were randomly assigned to one of two treatment groups: (1) cholecalciferol (vitamin D3) 200,000 IU as one dose at study entry plus genistein (G-2535), 600 mg daily or (2) placebo cholecalciferol day 1 and placebo genistein PO daily for 21-28 days prior to radical prostatectomy. Serum and tissue analyses were performed and side-effects recorded. Results: A total of 15 patients were enrolled, 8 in the placebo arm and 7 in the vitamin D3 + genistein (VD + G) arm. All patients were compliant and completed the study. No significant differences in side effect profiles were noted. Utilization of the VD + G trended toward increased calcitriol serum concentrations when compared to placebo (0.104 ± 0.2 vs. 0.0013 ± 0.08; p=0.08); however, prostate tissue levels did not increase. Calcidiol levels did not change (p=0.5). Immunohistochemistry for marker analyses using VECTRA automated quantitation revealed a increase in AR expression (p=0.04) and a trend toward increased

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

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W.; Herrmann, T. [Univ. of Technology, Dresden (Germany). Dept. of Radiotherapy and Radiooncology, Medical Faculty Carl Gustav Carus

    2007-03-15

    Purpose: To investigate the efficacy and safety of Wobe-Mugos {sup 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 {sup registered} E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. Results: Wobe-Mugos {sup 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 {sup registered} E group. Conclusion: The present study failed to demonstrate any effect of treatment with Wobe-Mugos {sup 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.)

  20. Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study.

    Science.gov (United States)

    Yokota, T; Ogawa, T; Takahashi, S; Okami, K; Fujii, T; Tanaka, K; Iwae, S; Ota, I; Ueda, T; Monden, N; Matsuura, K; Kojima, H; Ueda, S; Sasaki, K; Fujimoto, Y; Hasegawa, Y; Beppu, T; Nishimori, H; Hirano, S; Naka, Y; Matsushima, Y; Fujii, M; Tahara, M

    2017-05-05

    Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March

  1. The ethics of placebo-controlled trials: methodological justifications.

    Science.gov (United States)

    Millum, Joseph; Grady, Christine

    2013-11-01

    The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling.

  2. Placebo-controlled trials and the Declaration of Helsinki.

    Science.gov (United States)

    Lewis, John A; Jonsson, Bertil; Kreutz, Gottfried; Sampaio, Cristina; van Zwieten-Boot, Barbara

    2002-04-13

    A revised version of the Declaration of Helsinki, issued in October, 2000, remains a vital expression of medical ethics, and deserves unanimous support. A strict interpretation of the declaration seems to rule out clinical trials that use a placebo control group whenever licensed therapeutic methods already exist, preferring active controls. Although the efficacy of some new medicines can be satisfactorily established without the use of a placebo, for others the judicious use of placebo remains essential to establish their effectiveness.

  3. An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia

    DEFF Research Database (Denmark)

    Pauer, Lynne; Winkelmann, Andreas; Arsenault, Pierre

    2011-01-01

    To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.......To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States....

  4. Effect of the mGluR5-NAM Basimglurant on Behavior in Adolescents and Adults with Fragile X Syndrome in a Randomized, Double-Blind, Placebo-Controlled Trial: FragXis Phase 2 Results.

    Science.gov (United States)

    Youssef, Eriene A; Berry-Kravis, Elizabeth; Czech, Christian; Hagerman, Randi J; Hessl, David; Wong, Chin Y; Rabbia, Michael; Deptula, Dennis; John, Amy; Kinch, Russell; Drewitt, Philip; Lindemann, Lothar; Marcinowski, Moritz; Langland, Rachel; Horn, Carsten; Fontoura, Paulo; Santarelli, Luca; Quiroz, Jorge A

    2017-08-17

    Preclinical data suggest that inhibition of the metabotropic glutamate receptor 5 (mGluR5) receptor might hold therapeutic benefits in Fragile X syndrome (FXS). Treatment of Fmr1 knockout mice with mGluR5-negative allosteric modulators (NAMs) has been reported to correct a broad range of phenotypes related to FXS. The early short-term clinical trials with mGluR5 NAMs, including basimglurant, assessing the effects in individuals with FXS, were supportive of further exploration in larger, well-controlled trials. We evaluated basimglurant, a potent and selective mGluR5 NAM, in a 12-week, double-blind, parallel-group study of 183 adults and adolescents (aged 14-50, mean 23.4 years) with FXS. Individuals with an FMR1 full mutation were randomized to placebo or one of two doses of basimglurant. The primary efficacy endpoint was the change from baseline in behavioral symptoms using the Anxiety Depression and Mood Scale (ADAMS) total score. All treatment arms showed marked behavioral improvements from baseline to week 12 with less improvement in the basimglurant 1.5 mg arm than placebo; however, basimglurant 0.5 mg was inferior to placebo in the ADAMs total score. Treatment with basimglurant was overall well-tolerated. A higher incidence of adverse events classified as psychiatric disorders were reported in patients treated with basimglurant, including three patients with hallucinations or psychosis. In this phase 2 clinical trial, basimglurant did not demonstrate improvement over placebo. Evaluation of the overall risk-benefit in younger patient populations is an important consideration for the design of potential further investigations of efficacy with this class of medications.Neuropsychopharmacology advance online publication, 20 September 2017; doi:10.1038/npp.2017.177.

  5. Assessment of human immune responses to H7 avian influenza virus of pandemic potential: results from a placebo-controlled, randomized double-blind phase I study of live attenuated H7N3 influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Larisa Rudenko

    Full Text Available INTRODUCTION: Live attenuated influenza vaccines (LAIVs are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double-blinded randomized placebo-controlled phase I clinical trial of cold-adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults. OBJECTIVE: The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential. METHODS AND FINDINGS: Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo. The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person-to-person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two-dose immunization resulted in measurable serum and local antibody production and in generation of antigen-specific CD4⁺ and CD8⁺ memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus-specific T cells showed that the majority (86.2% of vaccine recipients developed serum and/or local antibodies responses and generated CD4⁺ and CD8⁺ memory T cells. CONCLUSIONS: The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus. TRIAL REGISTRATION: ClinicalTrials.gov NCT01511419.

  6. Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moderate-to-severe rheumatoid arthritis and inadequate response to TNF inhibitors: results of a randomised, double-blind, placebo-controlled, phase 3 study

    Science.gov (United States)

    Schiff, Michael; Combe, Bernard; Dörner, Thomas; Kremer, Joel M; Huizinga, Thomas W; Veenhuizen, Melissa; Gill, Anne; Komocsar, Wendy; Berclaz, Pierre-Yves; Ortmann, Robert; Lee, Chin

    2015-01-01

    Background Tabalumab is a human monoclonal antibody that neutralises B-cell activating factor. Objectives To evaluate tabalumab efficacy and safety in patients with rheumatoid arthritis (RA). Methods This phase 3, randomised, double-blind, placebo-controlled study evaluated 456 patients with active RA after 24-week treatment with subcutaneous tabalumab (120 mg every 4 weeks (120/Q4W) or 90 mg every 2 weeks (90/Q2W)) versus placebo, with loading doses (240 or 180 mg) at week 0. Patients were allowed background disease-modifying antirheumatic drugs and previously discontinued ≥1 tumour necrosis factor α inhibitors for lack of efficacy/intolerance. Primary end point was American College of Rheumatology 20% (ACR20) response at 24 weeks. This study was terminated early due to futility. Results Most patients had moderate-to-high baseline disease activity. There was no significant difference in week 24 ACR20 responses between 120/Q4W, 90/Q2W, and placebo (17.6%, 24.3%, 20%) per non-responder imputation analysis. Mean percent changes in CD20+ B-cell count (−10.8%, −9.6%, +10.9%) demonstrated expected pharmacodynamic effects. Treatment-emergent adverse events (AEs) were similar (59.5%, 51.7%, 52.6%), as were AE discontinuations (2.6%, 2.7%, 2.6%), serious AEs (4.6%, 4.1%, 3.9%), serious infectious events (1.3%, 0, 0) and events of interest: infections (23.5%, 25.9%, 24%), injection site reactions (13.1%, 25.8%, 11%) and allergy/hypersensitivity (3.9%, 4.1%, 3.9%) reports. Incidence of treatment-emergent antidrug antibodies was similar to placebo (3.9%, 4.8%, 3.9%). No deaths or new/unexpected safety findings were reported. Conclusions Tabalumab did not demonstrate clinical efficacy in patients with RA in this phase 3 study, despite evidence of biological activity. There were no notable differences in safety parameters between tabalumab treatment groups and placebo. Trial registration number: NCT01202773. PMID:26535134

  7. Placebo-induced decrease in fatigue: evidence for a central action on the preparatory phase of movement.

    Science.gov (United States)

    Piedimonte, Alessandro; Benedetti, Fabrizio; Carlino, Elisa

    2015-02-01

    Placebos have been found to affect a number of pathological processes and physiological functions through expectations of clinical improvement. Recently, the study of the placebo effect has moved from the clinical to the physical performance setting, wherein placebos can boost performance by increasing muscle work and by decreasing perceived exertion. However, nothing is known about the neurobiological underpinnings of this phenomenon. Here we show for the first time that a placebo, which subjects believed to be endurance-increasing caffeine, reduces fatigue by acting at the central level on the preparatory phase of movement. In fact, we recorded the readiness potential, which is the expression of the preparatory phase of movement at the level of the supplementary motor area, during repeated flexions of the index finger in a control group that did not receive any treatment and in a placebo group that received placebo caffeine. In the control group, as the number of flexions increased, both fatigue and readiness potential amplitude increased. By contrast, in the placebo group, as the number of flexions increased we found a decrease in perceived exertion along with no increase in readiness potential amplitude. This placebo-induced modulation of the readiness potential suggests that placebos reduce fatigue by acting centrally during the anticipatory phase of movement, thus emphasizing the important role of the central nervous system in the generation of fatigue.

  8. [Placebo control and clinical trial of Chinese medicine].

    Science.gov (United States)

    Wu, Jing

    2010-10-01

    World Health Organization aims to develop safe, effective and practical traditional medicine. Traditional Chinese medicine (TCM) and other complementary and alternative medicine are being recognized in the whole world nowadays. However, the definite effect of Chinese medicine is still in need of scientific research proof. Placebo control is of equal importance to active control and blank control in clinical trial of TCM. This article briefly reviewed the importance of placebo control and commented on its present situation in clinical trial of TCM. This article also brought up the preliminary proposals of placebo application in TCM clinical trial. We should emphasize scientific placebo preparation and good design of placebo-controlled trial, which are directed by International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. A good clinical trial project will avoid unnecessary wastes and provide safe and effective treatment for people.

  9. Phase III Double-Blind, Placebo-Controlled Study of Gabapentin for the Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy, NCCTG N08C3 (Alliance)

    Science.gov (United States)

    Barton, Debra L.; Thanarajasingam, Gita; Sloan, Jeff A.; Diekmann, Brent; Fuloria, Jyotsna; Kottschade, Lisa A.; Lyss, Alan P.; Jaslowski, Anthony J.; Mazurczak, Miroslaw A.; Blair, Scott C.; Terstriep, Shelby; Loprinzi, Charles L.

    2014-01-01

    BACKGROUND Despite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC). METHODS Participants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2–4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2–6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher’s exact test. RESULTS Four hundred thirty patients were enrolled in this study. Forty-seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P = .23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was <2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects. CONCLUSIONS In this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients. PMID:25043153

  10. LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases--a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial

    Directory of Open Access Journals (Sweden)

    Schimanski Carl

    2012-04-01

    Full Text Available Abstract Background 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods/Design This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg maintenance doses at 6-week (years 1&2 and 12-week (year 3 intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS time between groups. Secondary endpoints are overall survival (OS time, safety, tolerability, RFS/OS in MUC-1 positive

  11. Diclofenac epolamine plus heparin plaster versus diclofenac epolamine plaster in mild to moderate ankle sprain: a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase III trial.

    Science.gov (United States)

    Costantino, Cosimo; Kwarecki, Jacek; Samokhin, Anatoly V; Mautone, Giuseppe; Rovati, Stefano

    2011-01-01

    In general sports, ankle sprain is the most frequently reported ankle injury and can cause chronic lateral ankle pain and tenderness. Treatment with NSAIDs is preferred, and several topical NSAID formulations are now available, helping to avoid the systemic adverse events typically associated with oral preparations. To compare the efficacy and tolerability of a newly developed fixed-dose diclofenac epolamine (diclofenac hydroxyethylpyrrolidine, DHEP)/heparin plaster (Flectoparin® Tissugel) with that of a DHEP (Flector EP Tissugel®) or placebo plaster in the treatment of mild to moderate ankle sprain in adults. This was a randomized, double-blind, parallel-group, placebo-controlled, multicentre, phase III study conducted in the emergency medical centres of hospitals or private clinics in Europe. Outpatients aged 18-65 years who had suffered an acute ankle sprain (O'Donoghue grade I or II in severity, with external lateral ligament involvement) within the previous 48 hours and had peri-malleolar oedema were eligible for inclusion. A total of 430 patients were randomized to receive a DHEP/heparin 1.3%/5600 IU (n = 142), DHEP 1.3% (n = 146) or placebo (n = 142) plaster, applied once daily to the injured ankle for a total of 7 days. The primary endpoint was the mean change from baseline in pain on movement on day 3, as measured by a visual analogue scale (VAS). The DHEP/heparin plaster was associated with a significantly (p = 0.002) greater mean reduction from baseline in pain on movement after 3 days of treatment than the DHEP plaster (-24.2 vs -18.8 mm VAS), with each active treatment providing significantly (p ≤ 0.005) greater pain relief than placebo (-13.7 mm VAS). Both DHEP/heparin and DHEP were also effective in relieving other measures of pain, with DHEP/heparin recipients experiencing significantly less daily pain while leaning on the injured limb than DHEP recipients (p plaster and DHEP plaster were both well tolerated, with

  12. Antioxidant therapy for chronic hepatitis C after failure of interferon: Results of phase Ⅱ randomized, double-blind placebo controlled clinical trial

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology. RESULTS: Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part Ⅱ of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points. CONCLUSION: Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.

  13. A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence.

    Science.gov (United States)

    Ryan, Megan L; Falk, Daniel E; Fertig, Joanne B; Rendenbach-Mueller, Beatrice; Katz, David A; Tracy, Katherine A; Strain, Eric C; Dunn, Kelly E; Kampman, Kyle; Mahoney, Elizabeth; Ciraulo, Domenic A; Sickles-Colaneri, Laurie; Ait-Daoud, Nassima; Johnson, Bankole A; Ransom, Janet; Scott, Charles; Koob, George F; Litten, Raye Z

    2017-04-01

    Alcohol use disorder has been linked to dysregulation of the brain stress systems, producing a negative emotional state leading to chronic relapsing behavior. Vasopressin receptors appear to have a regulatory role in stress, anxiety, and alcohol. This study evaluated the novel compound, ABT-436, a V1b receptor antagonist, in alcohol-dependent participants in a 12-week clinical trial. Men and women (n=150) who met criteria for DSM-IV alcohol dependence were recruited across four sites. Participants received double-blind ABT-436 or placebo, and a computerized behavioral intervention. ABT-436 was titrated to 800 mg/day during weeks 2-12. Although the primary outcome, percentage of heavy drinking days, was lower in participants receiving ABT-436 compared with placebo, this difference was not statistically significant (31.3 vs 37.6, respectively; p=0.172; d=0.20). However, participants receiving ABT-436 had significantly greater percentage of days abstinent than those receiving placebo (51.2 vs 41.6, respectively; p=0.037; d=0.31). No significant differences were found between treatment groups on any other measures of drinking, alcohol craving, or alcohol-related consequences. Smokers receiving ABT-436 smoked significantly fewer cigarettes per week than those receiving placebo (p=0.046). ABT-436 was well tolerated, with diarrhea (mild-to-moderate severity) being the most common side effect. In subgroup analyses, participants with relatively higher baseline levels of stress responded better to ABT-436 than placebo on select drinking outcomes, suggesting there may be value in testing medications targeting the vasopressin receptor in high stress, alcohol-dependent patients.

  14. Desvenlafaxine 50 and 100 mg/d versus placebo for the treatment of major depressive disorder: a phase 4, randomized controlled trial.

    Science.gov (United States)

    Clayton, Anita H; Tourian, Karen A; Focht, Kristen; Hwang, Eunhee; Cheng, Ru-Fong J; Thase, Michael E

    2015-05-01

    To assess short-term efficacy and safety of desvenlafaxine 50 and 100 mg/d versus placebo for treating major depressive disorder (MDD). Assessment of sexual function was a secondary objective. Outpatients (≥ 18 years) who met criteria for MDD from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and had screening and baseline 17-item Hamilton Depression Rating Scale (HDRS17) total scores ≥ 20 were randomly assigned to placebo or desvenlafaxine 50 or 100 mg/d in an 8-week study conducted from October 2011 to August 2012. The primary efficacy end point was change from baseline in HDRS17 total score at week 8, analyzed using a mixed-effects model for repeated measures. Sexual function was assessed using the Arizona Sexual Experiences Scale (ASEX). The safety population included 909 patients (intent-to-treat population, n = 886). Significantly greater improvement in adjusted mean HDRS17 total score from baseline to week 8 was observed for desvenlafaxine 50 mg (-11.28; P = .006) and desvenlafaxine 100 mg (-11.67; P desvenlafaxine versus placebo for change from baseline in ASEX total and all item scores found P > .05, with no adjustment for multiplicity. Rates of sexual dysfunction based on ASEX were comparable among treatment groups. These results support previous findings demonstrating antidepressant efficacy, safety, and tolerability of desvenlafaxine 50 and 100 mg/d versus placebo. Sexual function was comparable between desvenlafaxine and placebo. ClinicalTrials.gov identifier: NCT01432457. © Copyright 2015 Physicians Postgraduate Press, Inc.

  15. Safety of placebo controls in pediatric hypertension trials.

    Science.gov (United States)

    Smith, P Brian; Li, Jennifer S; Murphy, M Dianne; Califf, Robert M; Benjamin, Daniel K

    2008-04-01

    Many clinical trials, including those in pediatric populations, use a placebo arm for medical conditions for which there are readily available therapeutic interventions. Several short-term efficacy trials of antihypertensive medications performed in response to Food and Drug Administration-issued written requests have used a placebo arm; whether the use of a placebo arm is safe in children with hypertension is unknown. We sought to define the rates of adverse events in 10 short-term antihypertensive trials to determine whether these trials resulted in increased risk to pediatric patients receiving placebo. We combined patient-level data from 10 antihypertensive efficacy trials performed in pediatric patients that were submitted to the Food and Drug Administration from 1998 to 2005. We determined the number and type of all of the adverse events reported during the placebo-controlled portion of the clinical trials and compared these numbers between the patients who received placebo and those who received active drug. Among the 1707 children in the 10 studies, we observed no differences in the rates of adverse events reported between the patients who received placebo and those who received active drug. Only 5 patients suffered a serious adverse event during the trials; none were thought by the investigators to be related to study drug, and only 1 occurred in a patient receiving placebo. Short-term exposure to placebo in pediatric trials of antihypertensive medications appears to be safe.

  16. Placebo-controlled dose-ranging phase 2 study of subcutaneously administered LHRH antagonist cetrorelix in patients with symptomatic benign prostatic hyperplasia.

    Science.gov (United States)

    Debruyne, Frans; Gres, Arkadij A; Arustamov, Dmitrii L

    2008-07-01

    Pilot studies with daily dosing suggested the use of the luteinizing hormone-releasing hormone antagonist cetrorelix (CET) for the treatment of symptoms from benign prostatic hyperplasia (BPH). To assess efficacy and safety of three dosing schemes of CET in patients with symptomatic BPH. After a run-in period with 4 weekly injections of placebo, 140 patients with an international prostate symptoms score (IPSS) > or =13 and a peak urinary flow rate (PFR) 5-13ml/s were randomly allocated to 4 treatment groups; patients with residual urine volume of >350ml were excluded. Patients received either CET at dosages of 5mg/wkx4, 10mg/2 wkx2 or 10mg/wkx4 or placebo. IPSS, PFR and mean uroflow, residual urinary volume, prostate volume, plasma testosterone, quality of life, and sexual function were evaluated over a total of 20 wk after randomization. Of 140 randomized patients, one patient did not complete treatment, 5 others dropped out off-treatment, before week 12 evaluation of the primary end point. In all CET groups a rapid improvement in mean IPSS was obtained, with a peak effect of -5.4 to -5.9 (placebo: -2.8). After all dosages of CET given, changes from baseline and differences to placebo were statistically significant up to week 20. Similarly, secondary parameters showed a significant, rapid, and persistent improvement for all CET dosages. All dosage regimens were well tolerated. The study evaluated a single treatment course only; further studies with repeated treatment courses will be required to establish a dose regimen for long-term disease management. At all dosage regimens tested, CET was safe and effective in patients with symptomatic BPH, with a trend towards a more rapid onset of effect for the CET 10mg/wkx4 regimen. Response persisted up to the end of follow-up, 16 wk after the last dose.

  17. A randomized placebo-controlled phase Ia malaria vaccine trial of two virosome-formulated synthetic peptides in healthy adult volunteers.

    Directory of Open Access Journals (Sweden)

    Blaise Genton

    Full Text Available BACKGROUND AND OBJECTIVES: Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides. The specific objective was to demonstrate the safety and immunogenicity of two virosome-formulated P. falciparum protein derived synthetic peptide antigens given in two different doses alone or in combination. METHODOLOGY/PRINCIPAL FINDINGS: The design was a single blind, randomized, placebo controlled, dose-escalating study involving 46 healthy Caucasian volunteers aged 18-45 years. Five groups of 8 subjects received virosomal formulations containing 10 microg or 50 microg of AMA 49-CPE, an apical membrane antigen-1 (AMA-1 derived synthetic phospatidylethanolamine (PE-peptide conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP derived synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 6 subjects received unmodified virosomes. Virosomal formulations of the antigens (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, respectively or unmodified virosomes were injected i. m. on days 0, 60 and 180. In terms of safety, no serious or severe adverse events (AEs related to the vaccine were observed. 11/46 study participants reported 16 vaccine related local AEs. Of these 16 events, all being pain, 4 occurred after the 1(st, 7 after the 2(nd and 5 after the 3(rd vaccination. 6 systemic AEs probably related to the study vaccine were reported after the 1(st injection, 10 after the 2(nd and 6 after the 3(rd. Generally, no difference in the distribution of the systemic AEs between either the doses applied (10 respectively 50 microg or the synthetic antigen vaccines (PEV301 and PEV302 used for immunization was found. In terms of immunogenicity, both PEV301 and PEV302

  18. Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue: a safety assessment: a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial.

    Science.gov (United States)

    Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María; Martínez-Sánchez, Patricia; Rodríguez-Frutos, Berta; Ruiz-Ares, Gerardo; Lara, Manuel Lara; Gimeno, Blanca Fuentes

    2014-01-01

    Few studies have evaluated the possible beneficial effect of the administration of stem cells in the early stages of stroke. Intravenous administration of allogeneic mesenchymal stem cells (MSCs) from adipose tissue in patients with acute stroke could be a safe therapy for promoting neurovascular unit repair, consequently supporting better functional recovery. We aim to assess the safety and efficacy of MSC administration and evaluate its potential as a treatment for cerebral protection and repair. A Phase IIa, prospective, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Twenty patients presenting acute ischemic stroke will be randomized in a 1:1 proportion to treatment with allogeneic MSCs from adipose tissue or to placebo (or vehicle) administered as a single intravenous dose within the first 2 weeks after the onset of stroke symptoms. The patients will be followed up for 2 years. Primary outcomes for safety analysis: adverse events (AEs) and serious AEs; neurologic and systemic complications, and tumor development. Secondary outcomes for efficacy analysis: modified Rankin Scale; NIHSS; infarct size; and biochemical markers of brain repair (vascular endothelial growth factor, brain-derived neurotrophic factor, and matrix metalloproteinases 9). To our knowledge, this is the first, phase II, pilot clinical trial to investigate the safety and efficacy of intravenous administration of allogeneic MSCs from adipose tissue within the first 2 weeks of stroke. In addition, its results will help us define the best criteria for a future phase III study. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI-refractory, differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Brose Marcia S

    2011-08-01

    Full Text Available Abstract Background The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI-refractory DTC. Methods/design DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles, whereas safety will be evaluated every 28 days (1 cycle for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS; patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate

  20. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia.

    Science.gov (United States)

    Papanicolaou, D A; Ather, S N; Zhu, H; Zhou, Y; Lutkiewicz, J; Scott, B B; Chandler, J

    2013-01-01

    Sarcopenia, the age-related loss of muscle mass [defined as appendicular LBM/Height2 (aLBM/ht2) below peak value by>1SD], strength and function, is a major contributing factor to frailty in the elderly. MK-0773 is a selective androgen receptor modulator designed to improve muscle function while minimizing effects on other tissues. The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass (LBM) in sarcopenic frail elderly women treated with MK-0773 relative to placebo. This was a randomized, double-blind, parallel-arm, placebo-controlled, multicenter, 6-month study. Participants were randomized in a 1:1 ratio to receive either MK-0773 50mg b.i.d. or placebo; all participants received Vitamin D and protein supplementation. General community. 170 Women aged ≥65 with sarcopenia and moderate physical dysfunction. Dual energy X-ray absorptiometry, muscle strength and power, physical performance measures. Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo (p<0.001). Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6, but the mean difference between the two groups was not significant (p=0.269). Both groups showed significant improvement from baseline at Month 6 in physical performance measures, but there were no statistically significant differences between participants receiving MK-0773 and placebo. A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo, which resolved after discontinuation of study therapy. MK-0773 was generally well-tolerated with no evidence of androgenization. The MK-0773-induced increase in LBM did not translate to improvement in strength or function vs. placebo. The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation.

  1. Famotidine as a radioprotector for rectal mucosa in prostate cancer patients treated with radiotherapy. Phase I/II randomized placebo-controlled trial

    Energy Technology Data Exchange (ETDEWEB)

    Razzaghdoust, A. [Shahid Beheshti University of Medical Sciences, Department of Radiology, Faculty of Paramedical Sciences, Tehran (Iran, Islamic Republic of); Mozdarani, H. [Tarbiat Modares University, Department of Medical Genetics, Faculty of Medical Sciences, Tehran (Iran, Islamic Republic of); Mofid, B. [Shohada-e- Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Department of Radiotherapy, Tehran (Iran, Islamic Republic of)

    2014-08-15

    Acute bowel toxicity significantly affects the quality of life of patients treated with pelvic radiotherapy. This study was performed to assess whether pretreatment with famotidine can reduce acute radiation toxicities in patients undergoing radiotherapy for prostate cancer. Between April 2012 and February 2013, 36 patients undergoing radiotherapy for prostate cancer were enrolled to receive either placebo or famotidine. The patients received external-beam radiotherapy up to 70 Gy at daily fractions of 1.8-2 Gy (5 days/week). Oral famotidine 40 mg (80 mg/day) or placebo was administered twice daily (4 and 3 h prior to each radiotherapy fraction). Bowel and bladder acute toxicities were evaluated weekly during radiotherapy and once thereafter according to RTOG grading criteria. Famotidine was well tolerated. No grade III or higher acute toxicities were noted in the two groups. Grade II rectal toxicity developed significantly more often in patients receiving placebo than in patients receiving famotidine (10/18 vs. 2/16, p = 0.009). Moreover, no rectal bleeding occurred in the famotidine group, while 5 patients in the placebo group experienced rectal bleeding during treatment (p = 0.046). The duration of rectal toxicity in the radiotherapy course was also reduced in the famotidine group (15.7 vs. 25.2 days, p = 0.027). No significant difference between the two groups was observed in terms of urinary toxicity. We demonstrated for the first time that famotidine significantly reduces radiation-induced injury on rectal mucosa representing a suitable radioprotector for patients treated with radiotherapy for prostate cancer. (orig.) [German] Die akute Darmtoxizitaet in der Strahlentherapie beeinflusst massgeblich die Lebensqualitaet der Patienten. Die Studie dient zur Klaerung des Famotidineinsatzes in der Vorbehandlung von Prostatakarzinompatienten zur Reduktion der Strahlenbelastung waehrend der Strahlentherapie. Von April 2012 bis Februar 2013 wurden 36

  2. A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.

    Directory of Open Access Journals (Sweden)

    Luciana Cadore Stefani

    Full Text Available Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT and the pressure pain tolerance (PPTo. Quantitative sensory testing (QST was used to measure the heat pain threshold (HPT and the heat pain tolerance (HPTo. Sedation was assessed with a visual analogue scale and bispectral analysis.Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg and the highest (0.25 mg/kg melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R(2  = 0.492 for HPT, R(2  = 0.538 for PPT, R(2  = 0.558 for HPTo and R(2  = 0.584 for PPTo.The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec: (U1111

  3. Effect of a prostaglandin - given rectally for prevention of radiation-induced acute proctitis - on late rectal toxicity. Results of phase III randomized, placebo-controlled, double-blind study

    Energy Technology Data Exchange (ETDEWEB)

    Kertesz, Tereza; Herrmann, Markus K.A.; Christiansen, Hans; Hermann, Robert M.; Hess, Clemens F.; Hille, Andrea [Dept. of Radiotherapy and Radiooncology, Univ. of Goettingen (Germany); Zapf, Antonia [Dept. of Medical Statistics, Univ. of Goettingen (Germany); Pradier, Olivier [Dept. of Radiotherapy and Radiooncology, Univ. of Brest (France); Schmidberger, Heinz [Dept. of Radiotherapy and Radiooncology, Univ. of Mainz (Germany)

    2009-09-15

    Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

  4. A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers.

    Directory of Open Access Journals (Sweden)

    Vincenzo Libri

    Full Text Available BACKGROUND: SRT2104 has been developed as a selective small molecule activator of SIRT1, a NAD(+-dependent deacetylase involved in the regulation of energy homeostasis and the modulation of various metabolic pathways, including glucose metabolism, oxidative stress and lipid metabolism. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. We report the first clinical trial of SRT2104 in elderly volunteers. METHODS: Oral doses of 0.5 or 2.0 g SRT2104 or matching placebo were administered once daily for 28 days. Pharmacokinetic samples were collected through 24 hours post-dose on days 1 and 28. Multiple pharmacodynamic endpoints were explored with oral glucose tolerance tests (OGTT, serum lipid profiles, magnetic resonance imaging (MRI for assessment of whole body visceral and subcutaneous fat, maximal aerobic capacity test and muscle 31P magnetic resonance spectroscopy (MRS for estimation of mitochondrial oxidative capacity. RESULTS: SRT2104 was generally safe and well tolerated. Pharmacokinetic exposure increased less than dose-proportionally. Mean Tmax was 2-4 hours with elimination half-life of 15-20 hours. Serum cholesterol, LDL levels and triglycerides decreased with treatment. No significant changes in OGTT responses were observed. 31P MRS showed trends for more rapid calculated adenosine diphosphate (ADP and phosphocreatine (PCr recoveries after exercise, consistent with increased mitochondrial oxidative phosphorylation. CONCLUSIONS: SRT2104 can be safely administered in elderly individuals and has biological effects in humans that are consistent with SIRT1 activation. The results of this study support further development of SRT2104 and may be useful in dose selection for future clinical trials in patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00964340.

  5. Adjuvant therapy with high dose vitamin D following primary treatment of melanoma at high risk of recurrence: a placebo controlled randomised phase II trial (ANZMTG 02.09 Mel-D).

    Science.gov (United States)

    Saw, Robyn P M; Armstrong, Bruce K; Mason, Rebecca S; Morton, Rachael L; Shannon, Kerwin F; Spillane, Andrew J; Stretch, Jonathan R; Thompson, John F

    2014-10-24

    Patients with primary cutaneous melanomas that are ulcerated and >2 mm in thickness, >4 mm in thickness and those with nodal micrometastases at diagnosis, have few options for adjuvant treatment. Recent studies have suggested a role for vitamin D to delay melanoma recurrence and improve overall prognosis. This is a pilot placebo-controlled randomised phase II trial to assess the feasibility, safety and toxicity of an oral loading dose of Vitamin D (500,000 IU) followed by an oral dose of 50,000 IU of Vitamin D monthly for 2 years in patients who have been treated for cutaneous melanoma by wide excision of the primary. Patients aged 18-79 years who have completed primary surgical treatment and have Stage IIb, IIc, IIIa (N1a, N2a) or IIIb (N1a, N2a) disease are eligible for randomisation 2:1 to active treatment or placebo. The primary endpoints are sufficiency of dose, adherence to study medication and safety of the drug. The secondary endpoints are participation and progression free survival. The study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number X09-0138. Effective, non-toxic adjuvant therapy for high risk primary melanoma is not currently available. Favorable outcomes of this phase II study will form the basis for a multi-centre phase III study to assess whether the addition of oral high-dose vitamin D therapy in patients who have completed primary treatment for melanoma and are at high risk of recurrence will: 1. prolong time to recurrence within 5 years 2. improve overall survival at 5 years and 3. be both safe and tolerable. 62 patients have been randomised since the study commenced in December 2010. Target accrual for the study has been met with 75 patients randomised between December 2010 and August 2014.The Mel-D trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG 02.09) TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN

  6. The efficacy and safety of S-flurbiprofen plaster in the treatment of knee osteoarthritis: a phase II, randomized, double-blind, placebo-controlled, dose-finding study

    Directory of Open Access Journals (Sweden)

    Yataba I

    2017-04-01

    not different across all four groups, and no severe AEs were observed. Conclusion: Clinically relevant pain relief was observed in all groups including placebo. Especially 40 mg showed remarkable pain relief in not only primary endpoint but also all the other endpoint with significant differences over placebo. The safety profile of SFPP 40 mg was not different from that of placebo. Therefore, 40 mg was determined as the optimal tested dose. Keywords: nonsteroidal anti-inflammatory drugs, patch, double-blind, visual analog scale, topical, optimal dose, randomized controlled trial

  7. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial

    NARCIS (Netherlands)

    Bois, A. du; Kristensen, G.; Ray-Coquard, I.; Reuss, A.; Pignata, S.; Colombo, N.; Denison, U.; Vergote, I.; Campo, J.M. Del; Ottevanger, P.B.; Heubner, M.; Minarik, T.; Sevin, E.; Gregorio, N. de; Bidzinski, M.; Pfisterer, J.; Malander, S.; Hilpert, F.; Mirza, M.R.; Scambia, G.; Meier, W.; Nicoletto, M.O.; Bjorge, L.; Lortholary, A.; Sailer, M.O.; Merger, M.; Harter, P.

    2016-01-01

    BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combin

  8. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

    NARCIS (Netherlands)

    Verhamme, C.; de Haan, R.J.; Vermeulen, M.; Baas, F.; de Visser, M.; van Schaik, I.N.

    2009-01-01

    ABSTRACT: BACKGROUND: High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-

  9. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

    Science.gov (United States)

    Simpson, Eric L; Bieber, Thomas; Guttman-Yassky, Emma; Beck, Lisa A; Blauvelt, Andrew; Cork, Michael J; Silverberg, Jonathan I; Deleuran, Mette; Kataoka, Yoko; Lacour, Jean-Philippe; Kingo, Külli; Worm, Margitta; Poulin, Yves; Wollenberg, Andreas; Soo, Yuhwen; Graham, Neil M H; Pirozzi, Gianluca; Akinlade, Bolanle; Staudinger, Heribert; Mastey, Vera; Eckert, Laurent; Gadkari, Abhijit; Stahl, Neil; Yancopoulos, George D; Ardeleanu, Marius

    2016-12-15

    Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. Methods In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. Results We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (Pphase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).

  10. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.

    Science.gov (United States)

    Erpenbeck, Veit J; Vets, Eva; Gheyle, Lien; Osuntokun, Wande; Larbig, Michael; Neelakantham, Srikanth; Sandham, David; Dubois, Gerald; Elbast, Walid; Goldsmith, Paul; Weiss, Markus

    2016-07-01

    We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1-3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2 , ∼20 hours). Steady state was achieved in 4 days with fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose-dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once-daily oral therapy for allergic diseases.

  11. Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial

    OpenAIRE

    Longo-Muñoz, F.; Argiles, G.; Tabernero, J.; Cervantes, A.; Gravalos, C.; Pericay, C.; Gil-Calle, S.; Mizuguchi, H; Carrato-Mena, A.; Limón, M. L.; Garcia-Carbonero, R.

    2016-01-01

    Purpose TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48...

  12. The Pharmacodynamic Impact of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, on Circulating Levels of Inflammatory Biomarkers in Patients with Psoriatic Arthritis: Substudy Results from a Phase III, Randomized, Placebo-Controlled Trial (PALACE 1

    Directory of Open Access Journals (Sweden)

    Peter H. Schafer

    2015-01-01

    Full Text Available Apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated effectiveness (versus placebo for treatment of active psoriatic arthritis in the psoriatic arthritis long-term assessment of clinical efficacy (PALACE phase III clinical trial program. Pharmacodynamic effects of apremilast on plasma biomarkers associated with inflammation were evaluated in a PALACE 1 substudy. Of 504 patients randomized in PALACE 1, 150 (placebo: n=51; apremilast 20 mg BID: n=51; apremilast 30 mg BID: n=48 provided peripheral blood plasma samples for analysis in a multiplexed cytometric bead array assay measuring 47 proteins associated with systemic inflammatory immune responses. Association between biomarker levels and achievement of 20% improvement from baseline in modified American College of Rheumatology (ACR20 response criteria was assessed by logistic regression. At Week 24, IL-8, TNF-α, IL-6, MIP-1β, MCP-1, and ferritin were significantly reduced from baseline with apremilast 20 mg BID or 30 mg BID versus placebo. ACR20 response correlated with change in TNF-α level with both apremilast doses. At Week 40, IL-17, IL-23, IL-6, and ferritin were significantly decreased and IL-10 and IL-1 receptor antagonists significantly increased with apremilast 30 mg BID versus placebo. In patients with active psoriatic arthritis, apremilast reduced circulating levels of Th1 and Th17 proinflammatory mediators and increased anti-inflammatory mediators.

  13. CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial.

    Science.gov (United States)

    Dubertret, L; Sterry, W; Bos, J D; Chimenti, S; Shumack, S; Larsen, C G; Shear, N H; Papp, K A

    2006-07-01

    Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1.0 mg kg-1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. Patients with moderate-to-severe plaque psoriasis [involvement of >or=10% of total body surface area and Psoriasis Area and Severity Index (PASI)>or=12.0 at screening] were randomized in a 2:1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving >or=75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29.5% for efalizumab compared with 2.7% for placebo among high-need patients (Pgeneral moderate-to-severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate-to-severe plaque psoriasis, including high-need patients.

  14. Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study.

    Science.gov (United States)

    Collaku, Agron; Yue, Yong; Reed, Kenneth

    2017-01-01

    Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID) in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0=not present to 10=unbearable) recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of this preliminary result in a larger, adequately powered study is needed.

  15. Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study

    Science.gov (United States)

    Collaku, Agron; Yue, Yong; Reed, Kenneth

    2017-01-01

    Background/objective Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. Methods This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID) in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0=not present to 10=unbearable) recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. Results A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Conclusion Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of this preliminary result in a larger, adequately powered study is needed. PMID:28356767

  16. 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...

  17. Testing Public Anxiety Treatments against a Credible Placebo Control

    Science.gov (United States)

    Duff, Desiree C.; Levine, Timothy R.; Beatty, Michael J.; Woolbright, Jessica; Park, Hee Sun

    2007-01-01

    Research investigating public speaking anxiety treatments is subject to demand effects. This study tests the relative effectiveness of systematic desensitization (SD) and multiple treatment method (MT) containing visualization therapy against no-treatment and credible placebo controls. Data (N = 238) were collected at six points in a public…

  18. Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial.

    Science.gov (United States)

    Longo-Muñoz, F; Argiles, G; Tabernero, J; Cervantes, A; Gravalos, C; Pericay, C; Gil-Calle, S; Mizuguchi, H; Carrato-Mena, A; Limón, M L; Garcia-Carbonero, R

    2017-02-01

    TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup. Primary and key secondary endpoints were evaluated in a post hoc analysis of the RECOURSE Spanish subgroup, using univariate and multivariate analyses. Safety and tolerability were reported with descriptive statistics. The RECOURSE Spanish subgroup included 112 patients (mean age 61 years, 62 % male). Median OS was 6.8 months in the TAS-102 group (n = 80) versus 4.6 months in the placebo group (n = 32) [HR = 0.47; 95 % confidence interval (CI): 0.28-0.78; P = 0.0032). Median PFS was 2.0 months in the TAS-102 group and 1.7 months in the placebo group (HR = 0.47; 95 % CI: 0.30-0.74; P = 0.001). Eighty (100 %) TAS-102 versus 31 (96.9 %) placebo patients had adverse events (AEs). The most common drug-related ≥Grade 3 AE was neutropenia (40 % TAS-102 versus 0 % placebo). There was 1 (1.3 %) case of febrile neutropenia in the TAS-102 group versus none in the placebo group. In the RECOURSE Spanish subgroup, TAS-102 was associated with significantly improved OS and PFS versus placebo, consistent with the overall RECOURSE population. No new safety signals were identified. CLINICALTRIALS. NCT01607957.

  19. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study

    Science.gov (United States)

    Giugliano, Robert P; Desai, Nihar R; Kohli, Payal; Rogers, William J; Somaratne, Ransi; Huang, Fannie; Liu, Thomas; Mohanavelu, Satishkumar; Hoffman, Elaine B; McDonald, Shannon T; Abrahamsen, Timothy E; Wasserman, Scott M; Scott, Robert; Sabatine, Marc S

    2013-01-01

    Summary Background LDL cholesterol (LDL-C) is a well established risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation. We therefore assessed the efficacy, safety, and tolerability of AMG 145, a human monoclonal IgG2 antibody against PCSK9, in stable patients with hypercholesterolemia on a statin. Methods In a phase 2, dose-ranging study done in 78 centres in the USA, Canada, Denmark, Hungary, and Czech Republic, patients (aged 18–80 years) with LDL-C greater than 2.2 mmol/L on a stable dose of statin (with or without ezetimibe), were randomly assigned equally, through an interactive voice response system, to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or matching placebo every 2 weeks; or subcutaneous injections of AMG 145 280 mg, 350 mg, or 420 mg, or matching placebo every 4 weeks. Everyone was masked to treatment assignment within the every 2 weeks and every 4 weeks schedules. The primary endpoint was the percentage change in LDL-C concentration from baseline after 12 weeks. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01380730. Findings 631 patients with hypercholesterolaemia were randomly assigned to AMG 145 70 mg (n=79), 105 mg (n=79), or 140 mg (n=78), or matching placebo (n=78) every 2 weeks; or AMG 145 280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79) every 4 weeks. At the end of the dosing interval at week 12, the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every 2 weeks (ranging from 41.8% to 66.1%; p<0.0001 for each dose vs placebo) and AMG 145 every 4 weeks (ranging from 41.8% to 50.3%; p<0.0001). No treatment-related serious adverse events occurred. The frequencies of treatment-related adverse events were similar in the AMG 145 and placebo groups (39 [8%] of 474 vs 11 [7%] of 155); none of these events were severe or life

  20. Patient-Reported Outcomes and the Association With Clinical Response in Patients With Active Psoriatic Arthritis Treated With Golimumab: Findings Through 2 Years of a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kavanaugh, Arthur; McInnes, Iain B; Krueger, Gerald G; Gladman, Dafna; Beutler, Anna; Gathany, Tim; Mack, Michael; Tandon, Neeta; Han, Chenglong; Mease, Philip

    2013-01-01

    Objective To evaluate the effect of golimumab on physical function, health-related quality of life (HRQOL), and productivity in psoriatic arthritis (PsA). Methods GO-REVEAL was a multicenter, randomized, placebo-controlled study. Adult patients with active PsA (n = 405) received golimumab (50 or 100 mg) or placebo every 4 weeks, with early escape at week 16 (placebo → 50 mg, 50 → 100 mg) or placebo crossover to golimumab 50 mg at week 24. Patient-reported outcomes included physical function (Health Assessment Questionnaire [HAQ] disability index [DI] score), HRQOL (36-item Short Form health survey [SF-36] mental component summary [MCS] and physical component summary [PCS] scores), and productivity (home/school/work). Clinical response was assessed using the 28-joint Disease Activity Score using the C-reactive protein level (DAS28-CRP) and the Psoriasis Area and Severity Index (PASI) score for arthritis and skin symptoms, respectively. Results At week 24, golimumab-treated patients had significant mean improvements in HAQ DI (0.36), SF-36 (PCS 7.83, MCS 3.84), and productivity (2.24) scores compared with placebo (−0.01, 0.67, −0.60, and 0.08, respectively; P <0.001 for all). Also, greater proportions of golimumab- than placebo-treated patients had clinically meaningful improvements in HAQ DI (≥0.30) and SF-36 PCS and MCS (≥5) scores at week 24 (P <0.05). Also at week 24, improvements in DAS28-CRP scores were significantly but moderately correlated with improvements in HAQ DI, SF-36 PCS, and productivity scores. Correlations between these patient-reported outcomes and improvements in PASI, enthesitis, and dactylitis scores were very weak. Improvements in HAQ DI, SF-36, and productivity scores were similar among all groups by week 52 and week 104 when including placebo → golimumab crossover patients. Conclusion Golimumab-treated patients had significant improvements in physical function, HRQOL, and productivity through week 24; these improvements

  1. Pain relief of sore throat with a new anti-inflammatory throat lozenge, ibuprofen 25 mg: A randomised, double-blind, placebo-controlled, international phase III study.

    Science.gov (United States)

    Bouroubi, Athmane; Donazzolo, Yves; Donath, Franck; Eccles, Ron; Russo, Marc; Harambillet, Nadine; Gautier, Stéphanie; Montagne, Agnès

    2017-09-04

    The aim of this study was to compare the efficacy and safety of a new oromucosal ibuprofen form, ibuprofen 25 mg lozenge, in single and repeat dosing for up to 4 days, to the matched placebo, in the treatment of acute sore throat pain in adults. In this randomised, double-blind, placebo-controlled trial, adult patients with non-streptococcal sore throat and signs of moderate-to-severe associated pain (≥5 on the objective Tonsillo-Pharyngitis Assessment 21-point scale and ≥60 mm on the subjective 0-100 mm visual analogue Sore Throat Pain Intensity Scale [STPIS]) were assigned ibuprofen 25 mg (n=194) or matching placebo (n=191) lozenge treatment. Efficacy was assessed (at the investigating centre up to 2 hours after first dosing, then on an ambulatory basis) by parameters derived from patient's scores on scales of pain relief, pain intensity, and global efficacy assessment. The primary efficacy end-point was the time-weighted TOTal PAin Relief (TOTPAR) over 2 hours after first dosing using the Sore Throat Relief Scale (STRS). Safety and local tolerability were assessed. Ibuprofen 25 mg was superior to placebo on numerous pain relief parameters; TOTPAR was significantly higher with ibuprofen 25 mg over 2 hours after first dosing (Prelief of sore throat pain and is as well tolerated as placebo. ClinicalTrials.gov, NCT01785862. © 2017 John Wiley & Sons Ltd.

  2. Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study

    OpenAIRE

    Collaku A; Yue Y.; Reed K

    2017-01-01

    Agron Collaku, Yong Yue, Kenneth Reed GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA Background/objective: Guaifenesin, an over-the-counter (OTC) expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. Methods: This multicenter, placebo-controlled, repeat-dose, parallel study randomly ass...

  3. Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

    2009-01-01

    The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

  4. Efficacy and safety of guaifenesin for upper back, neck, and shoulder pain: a Phase II proof-of-concept, multicenter, placebo-controlled, repeat-dose, parallel-group study

    Directory of Open Access Journals (Sweden)

    Collaku A

    2017-03-01

    Full Text Available Agron Collaku, Yong Yue, Kenneth Reed GlaxoSmithKline Consumer Healthcare, Parsippany, NJ, USA Background/objective: Guaifenesin, an over-the-counter (OTC expectorant, has exhibited muscle relaxant effects preclinically and clinically. This proof-of-principle study explored whether OTC doses of guaifenesin can provide relief from acute upper back, neck, or shoulder muscle spasm and pain. Methods: This multicenter, placebo-controlled, repeat-dose, parallel study randomly assigned adults experiencing acute pain and muscle spasm in their upper back, neck, or shoulder to guaifenesin 600 or 1200 mg or matched placebo twice daily (BID in a 2:2:1:1 ratio for 7 days. The primary end point was the change from baseline in muscle spasm relief, measured using an 11-point numeric rating scale (0= not present to 10= unbearable recorded twice daily and averaged over the 7-day treatment period. Analyses were performed using a linear mixed model that included treatment as a fixed effect and site as a random effect. Results: A total of 77 subjects were included in the 4 treatment groups. Least squares mean muscle spasm score over 7 days was 1.77 with guaifenesin 1200 mg, 1.42 with its matched placebo, 1.53 with guaifenesin 600 mg, and 1.74 with its matched placebo. Treatment with guaifenesin 1200 mg BID provided 25% greater reduction in mean muscle spasm over its matched placebo and 16% greater reduction than guaifenesin 600 mg BID. These differences were not statistically significant. Based on comparisons of absolute mean values, a consistent directional change in effect was observed, suggesting some benefit from placebo to lower-to-upper doses of guaifenesin with regard to muscle spasm, tension, pain, discomfort, and relaxation. No severe or serious adverse events were reported. Conclusion: Results suggest the potential for OTC dose of guaifenesin 1200 mg BID to provide symptomatic relief of upper back musculoskeletal pain and spasm. Confirmation of

  5. Veterinary clinical research database for homeopathy: placebo-controlled trials.

    Science.gov (United States)

    Clausen, J; Albrecht, H; Mathie, R T

    2013-04-01

    Veterinary homeopathy has led a somewhat shadowy existence since its first introduction. Only in the last three decades has the number of clinical trials increased considerably. This literature is generally not well perceived, which may be partly a consequence of the diffuse and somewhat inaccessible nature of some of the relevant research publications. The Veterinary Clinical Research Database for Homeopathy (VetCR) was launched in 2006 to provide information on existing clinical research in veterinary homeopathy and to facilitate the preparation of systematic reviews. The aim of the present report is to provide an overview of this first database on clinical research in veterinary homeopathy, with a special focus on its content of placebo controlled clinical trials and summarising what is known about placebo effects in animals. In April 2012, the VetCR database contained 302 data records. Among these, 203 controlled trials were identified: 146 randomised and 57 non-randomised. In 97 of those 203 trials, the homeopathic medical intervention was compared to placebo. A program of formal systematic reviews of peer-reviewed randomised controlled trials in veterinary homeopathy is now underway; detailed findings from the program's data extraction and appraisal approach, including the assessment of trial quality (risk of bias), will be reported in due course. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study

    Science.gov (United States)

    Landewé, R; Braun, J; Deodhar, A; Dougados, M; Maksymowych, W P; Mease, P J; Reveille, J D; Rudwaleit, M; van der Heijde, D; Stach, C; Hoepken, B; Fichtner, A; Coteur, G; de Longueville, M; Sieper, J

    2014-01-01

    Objectives To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Methods Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear. Results Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (−2.28 vs −0.40), BASDAI (−3.05 vs −1.05), and BASMI (−0.52 vs −0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported. Conclusions CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients. PMID:24013647

  7. 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.

    2015-01-01

    Background 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. Methods 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. Findings 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

  8. No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

    Science.gov (United States)

    Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

    2016-03-01

    The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

  9. Efficacy and safety of HL301 in the treatment of acute bronchitis and acute exacerbation of chronic bronchitis: a phase 2, randomized, double-blind, placebo-controlled, multicenter study.

    Science.gov (United States)

    Park, Myung Jae; Rhee, Chin Kook; Kim, Yee Hyung; Kim, Do Jin; Kim, Dong Gyu; Lee, Sang Yeub; Kim, Jae Yeol

    2017-05-01

    The efficacy and safety of Chinese herbs for symptomatic treatment of bronchitis is not well established. We evaluated the efficacy and safety of a combination product of seven herbs (HL301) for the treatment of acute bronchitis (AB) and acute exacerbation of chronic bronchitis (AECB) using a randomized, double-blind, placebo-controlled, multicenter trial design. A total of 160 patients with AB or with AECB were randomized to receive placebo or one of three doses of HL301 (0.6 g/day, 1.2 g/day, or 1.8 g/day) for a total of 7 days. The primary study endpoint was the change in bronchitis severity score (BSS) from the baseline visit (visit 2) to the end of treatment visit (visit 3). Other efficacy variables were percentage BSS systemic sign efficacy after treatment and change in individual BSS parameters after treatment. Changes in BSS from visit 2 to visit 3 in the three treatment groups (4.63 ± 2.24, 4.08 ± 1.63, and 4.15 ± 1.74 in the HL301 0.6 g/day, 1.2 g/day, and 1.8 g/day groups, respectively) were higher than that of the placebo group (2.88 ± 2.57) in the per protocol set (PPS) (P < .05), and it was also valid in the full analysis set (FAS). The number of participants whose symptoms (measured by BSS) improved at least 30% after treatment was higher in all three treatment groups compared to the placebo group in both the FAS and the PPS (P < .05, for all). Three different doses of HL301 (0.6 g/day, 1.2 g/day, and 1.8 g/day) were effective in decreasing the BSS index compared to placebo. HL301 may be effective for symptomatic treatment of both AB and AECB. Essential components of HL301 have not been delineated in the study and patients with AB and AECB were indiscriminately enrolled in the present study. Respective evaluation of the efficacy of HL301 for AB and AECB will be necessary in the future.

  10. Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group

    Science.gov (United States)

    Msellati, P.; Meda, N.; Leroy, V.; Likikouet, R.; Van de Perre, P.; Cartoux, M.; Bonard, D.; Ouangre, A.; Combe, P.; Gautier-Charpenti..., L.; Sylla-Koko, F.; Lassalle, R.; Dosso, M.; Welffens-Ekra, C.; Dabis, F.; Mandelbrot, L.

    1999-01-01

    OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Cote d'Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent. INTERVENTION: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth. MAIN OUTCOME MEASURES: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis. RESULTS: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively). CONCLUSION: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated. 


 PMID:10754950

  11. Aacap 2002 Research Forum: Placebo and Alternatives to Placebo in Randomized Controlled Trials in Pediatric Psychopharmacology

    Science.gov (United States)

    March, John; Kratochvil, Christopher; Clarke, Gregory; Beardslee, William; Derivan, Albert; Emslie, Graham; Green, Evelyn P.; Heiligenstein, John; Hinshaw, Stephen; Hoagwood, Kimberly; Jensen, Peter; Lavori, Philip; Leonard, Henrietta; McNulty, James; Michaels, M. Alex; Mossholder, Andrew; Osher, Trina; Petti, Theodore; Prentice, Ernest; Vitiello, Benedetto; Wells, Karen

    2004-01-01

    Objective: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized…

  12. Main results of the Ouabain and Adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT: a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin

    Directory of Open Access Journals (Sweden)

    Citterio Lorena

    2011-01-01

    Full Text Available Background The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP in some animal models and in humans. Methods OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect, subjects nested within sequence (random, period (fixed, and treatment (fixed. Results Among 410 analyzable patients (40.5% women; mean age, 48.4 years, the differences in the primary endpoint (rostafuroxin minus placebo ranged from -0.18 mm Hg (P = 0.90 on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04 on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03 for systolic office BP; 0.70 mm Hg (P = 0.08 for diastolic office BP; 0.36 mm Hg (P = 0.49 for 24-h systolic BP; and 0.05 mm Hg (P = 0.88 for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg and diastolic (-0.97 mm Hg office BPs decreased from week 5 to 10 (P for period effect ≤0.028, but carry-over effects were not significant (P ≥ 0.11. All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo. Conclusions In 5 concurrently running double-blind cross-over studies

  13. Trachyspermum ammi 10 % topical cream versus placebo on neuropathic pain, a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Petramfar, Peyman; Moein, Mahmoodreza; Samani, Soliman Mohammadi; Tabatabaei, Sayed Hamidreza; Zarshenas, Mohammad M

    2016-09-01

    A four-week, double-blind, randomized, placebo-controlled trial was conducted to assay the effectiveness of Ajwain 10 % (Trachyspermum ammi Sprague) topical cream on neuropathic pain. Intervention encompassed Ajwain 10 % and placebo creams. Ninety-two patients who specifically mentioned daily and nocturnal burning feet were randomly assigned to receive one of those interventions. Presence and decline in patients' numbness, tingling and allodynia were also evaluated. Major outcome measure was alteration in feet burning intensity (final week versus baseline week) regarding to a visual analog scale on a 0-10 cm scale (0 being "no pain", 10 being "worst pain"). Significant reduction in feet burning scores as well as numbness, tingling and allodynia were found in Ajwain group compared to placebo. This trial examining a cream of Ajwain essential oil versus placebo revealed the significance difference between two groups. This medicament can be a good candidate for the alleviation of feet burning, a neuropathic complication.

  14. PISA. The effect of paracetamol (acetaminophen and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690

    Directory of Open Access Journals (Sweden)

    Kappelle Jaap

    2002-03-01

    Full Text Available Abstract Background During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily and low dose (3 g daily paracetamol (acetaminophen in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. Aim The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. Design Seventy-five (3 × 25 patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

  15. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Bruchfeld, Annette; Roth, David; Martin, Paul; Nelson, David R; Pol, Stanislas; Londoño, Maria-Carlota; Monsour, Howard; Silva, Marcelo; Hwang, Peggy; Arduino, Jean-Marie; Robertson, Michael; Nguyen, Bach-Yen; Wahl, Janice; Barr, Eliav; Greaves, Wayne

    2017-08-01

    In the C-SURFER study, therapy with the all-oral elbasvir plus grazoprevir regimen for 12 weeks in patients with chronic hepatitis C virus (HCV) infection and stage 4-5 chronic kidney disease resulted in a high rate of virological cure compared with placebo. Here, we report sustained virological response (SVR), safety data, health-related quality-of-life (HRQOL), and virological resistance analyses in patients in C-SURFER who received immediate antiviral therapy or who received placebo before therapy. In this phase 3, multicentre, randomised, placebo-controlled study, we randomly assigned adults with HCV genotype 1 infection and stage 4-5 chronic kidney disease enrolled at 68 centres worldwide to either elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks (immediate treatment group) or placebo for 12 weeks followed by elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks beginning at week 16 (deferred treatment group). The primary safety and efficacy endpoints for the immediate treatment group and placebo phase of the deferred treatment group have been reported previously. Here, we report safety and efficacy data for the treatment phase of the deferred treatment group, as well as HRQOL assessed using the 36-Item Short Form Health Survey for all groups, and baseline and treatment-emergent resistance-associated substitutions (RASs). SVR at 12 weeks (SVR12) was assessed in the modified full analysis set (FAS), defined as all patients excluding those who did not receive at least one dose of study drug, who died, or who discontinued the study before the end of treatment for reasons determined to be unrelated to HCV treatment. This trial is registered with ClinicalTrials.gov, Number NCT02092350. Between March 30 and Nov 28, 2014, 235 patients were enrolled and received at least one dose of study drug. The modified FAS included 116 patients assigned to immediate treatment and 99 assigned to deferred treatment. 115 (99·1%; 95% CI 95·3-100·0) of

  16. A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III

    Directory of Open Access Journals (Sweden)

    Giuseppe Morgia

    2017-06-01

    Full Text Available Objective: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. Material and methods: From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A or treatment (Group B. Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95% and Calendula extract 80 mg (1 suppository/die for 1 month. Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT. Results: A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01, IIEF-5 (+ 3.5; p < 0.01, PEDT (-6.5; p < 0.01, peak flow (+2.8; p < 0.01 and VAS (-6.5; p < 0.01 with significant differences over placebo group (all p-value significant. Conclusions: In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of

  17. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

    DEFF Research Database (Denmark)

    Orwoll, Eric; Teglbjærg, Christence S; Langdahl, Bente Lomholt;

    2012-01-01

    Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to...

  18. Use of placebos in Phase 1 preventive HIV vaccine clinical trials.

    Science.gov (United States)

    Huang, Yunda; Karuna, Shelly T; Janes, Holly; Frahm, Nicole; Nason, Martha; Edlefsen, Paul T; Kublin, James G; Corey, Lawrence; McElrath, M Juliana; Gilbert, Peter B

    2015-02-04

    Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Improvements in productivity at paid work and within the household, and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomised placebo-controlled study

    Science.gov (United States)

    Kavanaugh, A; Gladman, D; van der Heijde, D; Purcaru, O; Mease, P

    2015-01-01

    Objectives To evaluate the effect of certolizumab pegol (CZP) on productivity outside and within the home, and on participation in family, social and leisure activities in adult patients with psoriatic arthritis (PsA). Methods RAPID-PsA (NCT01087788) is a phase 3, double-blind, placebo-controlled trial. 409 patients with active PsA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). The arthritis-specific Work Productivity Survey (WPS) assessed the impact of PsA on paid work and household productivity, and participation in social activities during the preceding month. WPS responses were compared between treatment arms using a non-parametric bootstrap-t method. Results At baseline, 56.6%, 60.1% and 61.5% of placebo, CZP 200 mg Q2W and CZP 400 mg Q4W patients were employed. By week 24, employed CZP patients reported an average of 1.0–1.8 and 3.0–3.9 fewer days of absenteeism and presenteeism, respectively, per month compared with 1.0 and 0.3 fewer days for placebo patients (p<0.05). Within the home, by week 24, CZP patients reported an average of 3.0–3.5 household work days gained per month versus 1.0 day for placebo (p<0.05). CZP patients also reported fewer days with reduced household productivity or days lost for participation in family, social and leisure activities. Improvements with CZP were seen as early as week 4 and continued to week 24. Conclusions CZP treatment significantly improved productivity at paid work and within the home, and resulted in greater participation in social activities for PsA patients. Trial registration number NCT01087788. PMID:24942382

  20. Rationale and design of LAPLACE-2: a phase 3, randomized, double-blind, placebo- and ezetimibe-controlled trial evaluating the efficacy and safety of evolocumab in subjects with hypercholesterolemia on background statin therapy.

    Science.gov (United States)

    Robinson, Jennifer G; Rogers, William J; Nedergaard, Bettina S; Fialkow, Jonathan; Neutel, Joel M; Ramstad, David; Somaratne, Ransi; Legg, Jason C; Nelson, Patric; Scott, Rob; Wasserman, Scott M; Weiss, Robert

    2014-04-01

    Low-density lipoprotein cholesterol (LDL-C) levels are significantly associated with atherosclerotic cardiovascular disease (ASCVD) risk, and studies using interventions that lower LDL-C levels have been shown to reduce the risk of ASCVD events and mortality. Statin treatment is the current first-line therapy for lowering LDL-C and reducing ASCVD risk. However, many patients are still unable to reach recommended LDL-C goals on maximally tolerated statin therapy. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL-C in phase 2 clinical trials when administered alone or in combination with a statin. The aim of this phase 3 study is to evaluate the efficacy of 12 weeks of subcutaneous evolocumab (vs placebo) administered every 2 weeks or every month in combination with a statin in patients with hypercholesterolemia and mixed dyslipidemia. This study will also provide comparative efficacy, safety, and tolerability data between evolocumab and ezetimibe when added to background atorvastatin therapy.

  1. Pregabalin for the treatment of abdominal adhesion pain: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Silverman, Ann; Samuels, Qiana; Gikas, Helen; Nawras, Ali

    2012-11-01

    Chronic pain related to postoperative abdominal adhesions is a common problem with no standard analgesic regimen currently established. In a double-blind, placebo-controlled trial, we examined the effects of pregabalin on pain modulation in patients with prior abdominal surgery and documented adhesion. The primary outcome measure was pain relief documented by a 2-point change on the Likert pain scale with a secondary pain measure of sleep interruption. A total of 18 women were randomized to receive either the drug (n = 11) or placebo (n = 7). Thirteen patients (eight pregabalin, five placebo) completed the blinded phase and 10 patients (seven pregabalin, three placebo) completed the open-label phase. Statistical analysis was performed in two settings: 1) Week 0 (as the baseline) through the end of Week 7 of the blinded fixed-dose phase; and 2) Week 7 (as the baseline) along With weeks 8 through 11 of the open-label phase. The pain score result from the blinded phase setting indicated that the amount of decrease was significantly greater in the drug group (P = 0.024), whereas the pain score result from the open-label setting indicated that the amount of decrease was significantly greater in the placebo group (P = 0.043). Only the sleep score result in the open-label setting was significantly greater in the placebo group (P = 0.024). We conclude that pregabalin significantly reduced patient-documented pain scores compared with placebo in our small cohort of patients with abdominal adhesion pain.

  2. 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.

  3. A double-blind placebo controlled trial of medroxyprogesterone acetate and cyproterone acetate with seven pedophiles.

    Science.gov (United States)

    Cooper, A J; Sandhu, S; Losztyn, S; Cernovsky, Z

    1992-12-01

    Seven of ten pedophiles in hospital completed a double-blind, placebo-controlled two-dose comparison of medroxyprogesterone acetate and cyproterone acetate. Sequential measures during the 28 week study were: patient self-reports, nurses' observations, phallometry, hormone levels and side-effects. The drugs, which performed equivalently, reduced sexual thoughts and fantasies, the frequency of early morning erections on awakening, the frequency and pleasure of masturbation, and level of sexual frustration. Penile responses were also reduced but to a lesser degree and were more variable. Serum testosterone FSH and LH all declined during drug administration, but by the end of the final placebo phase had essentially returned to (or exceeded) pre-drug values. Our experience suggests that only a minority of pedophiles are likely to accept libido-reducing drugs.

  4. Effects of dabigatran on the cellular and protein phase of coagulation in patients with coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel. Results from a prospective, randomised, double-blind, placebo-controlled study.

    Science.gov (United States)

    Franchi, Francesco; Rollini, Fabiana; Cho, Jung Rae; King, Rhodri; Phoenix, Fladia; Bhatti, Mona; DeGroat, Christopher; Tello-Montoliu, Antonio; Zenni, Martin M; Guzman, Luis A; Bass, Theodore A; Ajjan, Ramzi A; Angiolillo, Dominick J

    2016-03-01

    There is growing interest in understanding the effects of adding an oral anticoagulant in patients on dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and clopidogrel represent the most broadly utilised oral anticoagulant and P2Y12 receptor inhibitor, respectively. However, VKAs can interfere with clopidogrel metabolism via the cytochrome P450 (CYP) system which in turn may result in an increase in platelet reactivity. Dabigatran is a direct acting (anti-II) oral anticoagulant which does not interfere with CYP and has favourable safety and efficacy profiles compared with VKAs. The pharmacodynamic (PD) effects on platelet reactivity and clot kinetic of adjunctive dabigatran therapy in patients on DAPT are poorly explored. In this prospective, randomised, double-blind, placebo-controlled PD study, patients (n=30) on maintenance DAPT with aspirin and clopidogrel were randomised to either dabigatran 150 mg bid or placebo for seven days. PD testing was performed before and after treatment using four different assays exploring multiple pathways of platelet aggregation and fibrin clot kinetics: light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA), kaolin-activated thromboelastography (TEG) and turbidimetric assays. There were no differences in multiple measures of platelet reactivity investigating purinergic and non-purinergic signaling pathways assessed by LTA, MEA and TEG platelet mapping. Dabigatran significantly increased parameters related to thrombin activity and thrombus generation, and delayed fibrin clot formation, without affecting clot structure or fibrinolysis. In conclusion, in patients on DAPT with aspirin and clopidogrel, adjunctive dabigatran therapy is not associated with modulation of profiles of platelet reactivity as determined by several assays assessing multiple platelet signalling pathways. However, dabigatran significantly interferes with parameters related to thrombin activity and delays fibrin clot formation.

  5. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Berry-Kravis, Elizabeth; Des Portes, Vincent; Hagerman, Randi; Jacquemont, Sébastien; Charles, Perrine; Visootsak, Jeannie; Brinkman, Marc; Rerat, Karin; Koumaras, Barbara; Zhu, Liansheng; Barth, Gottfried Maria; Jaecklin, Thomas; Apostol, George; von Raison, Florian

    2016-01-13

    Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-C(FX)) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits.

  6. The Declaration of Helsinki and clinical trials: a focus on placebo-controlled trials in schizophrenia.

    Science.gov (United States)

    Carpenter, William T; Appelbaum, Paul S; Levine, Robert J

    2003-02-01

    The authors' goal was to consider ethical approaches to placebo-controlled clinical trials in the light of the evolving Declaration of Helsinki, with special attention to applications to research on schizophrenia. They review the Helsinki position on placebos, including the 2002 Clarification, exploring the potential negative effects of banning placebos in studies involving conditions for which at least partially effective treatments exist. The Clarification is examined as an approach to this issue that, in contrast to earlier formulations, better acknowledges the complexity of clinical research and the need for protocol-specific determinations. Placebo controls in schizophrenia studies are used to illustrate issues relevant to all clinical research on therapeutic interventions. The Helsinki Clarification provides a basis for operationalizing criteria for review of placebo use in clinical trials. Six criteria are proposed for judging the ethical acceptability of placebo controls, including the likelihood that the intervention being tested will have clinically significant advantages over existing treatments, the presence of compelling reasons for placebo use, subject selection that minimizes the possibility of serious adverse consequences, and a risk-versus-benefit analysis that favors the advantages from placebo use over the risks to subjects. The Helsinki Clarification constitutes an important advance in international approaches to placebo use, requiring protocol-by-protocol judgments on complex issues of clinical research ethics. When operationalized, it provides review boards with a useful methodology for reaching determinations on the appropriateness of placebo controls in particular studies.

  7. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study.

    Science.gov (United States)

    Harmatz, Paul; Giugliani, Roberto; Schwartz, Ida; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M Clara Sá; Wraith, J Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Yu, Zi-Fan; Wittes, Janet; Berger, Kenneth I; Newman, Mary S; Lowe, Ann M; Kakkis, Emil; Swiedler, Stuart J

    2006-04-01

    The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment. Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks. After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein. rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.

  8. Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial.

    Science.gov (United States)

    Misra, Usha Kant; Kalita, Jayantee; Yadav, Rama Kant

    2007-06-01

    The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.

  9. Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial.

    Science.gov (United States)

    Brodie, Martin J; Rosenfeld, William E; Vazquez, Blanca; Sachdeo, Rajesh; Perdomo, Carlos; Mann, Allison; Arroyo, Santiago

    2009-08-01

    To evaluate efficacy and safety of adjunctive treatment with rufinamide 1600 mg twice daily in subjects aged > or = 16 years with refractory partial seizures. This double-blind, placebo-controlled, randomized, parallel-group, multicenter trial included an 8-week baseline phase and a 13-week double-blind phase. Treatment was initiated with rufinamide 400 mg twice daily or placebo; rufinamide was titrated to 1600 mg twice daily. Percentage change in partial seizure frequency was the primary outcome measure. Secondary outcome measures included total partial seizure frequency and the percentage of subjects experiencing a >/=50% reduction in partial seizure frequency. Three hundred thirteen subjects were randomized; 156 subjects received rufinamide and 157 received placebo. Rufinamide-treated subjects experienced a 20.4% median reduction in partial seizure frequency relative to baseline, while placebo-treated subjects had an increase of 1.6% (p = 0.02). Exclusion of subjects taking carbamazepine in a post hoc analysis resulted in a reduction of 29.2% versus 0.7% in the placebo group (p = 0.05), whereas the treatment difference in subjects taking carbamazepine was not significant. Of rufinamide-treated subjects, 28.2% experienced a > or = 50% decrease in partial seizure frequency versus 18.6% of placebo-treated subjects (p = 0.04). The most common adverse events associated with rufinamide treatment were dizziness, nausea, diplopia, and ataxia; they occurred primarily during the titration phase. Adjunctive therapy with rufinamide 3200 mg/day compared with matching placebo demonstrated efficacy and was generally well tolerated in adults with partial seizures. Further study of this agent in adults with partial seizures taking a range of baseline AEDs is warranted.

  10. Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Schmitz-Winnenthal, Friedrich H; Hohmann, Nicolas; Niethammer, Andreas G; Friedrich, Tobias; Lubenau, Heinz; Springer, Marco; Breiner, Klaus M; Mikus, Gerd; Weitz, Jürgen; Ulrich, Alexis; Buechler, Markus W; Pianka, Frank; Klaiber, Ulla; Diener, Markus; Leowardi, Christine; Schimmack, Simon; Sisic, Leila; Keller, Anne-Valerie; Koc, Ruhan; Springfeld, Christoph; Knebel, Philipp; Schmidt, Thomas; Ge, Yingzi; Bucur, Mariana; Stamova, Slava; Podola, Lilli; Haefeli, Walter E; Grenacher, Lars; Beckhove, Philipp

    2015-04-01

    VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

  11. Fluoxetine for poststroke depression A randomized placebo controlled clinical trial

    Institute of Scientific and Technical Information of China (English)

    Yan Kong; Wanli Dong; Chunfeng Liu

    2007-01-01

    BACKGROUND: Studies have demonstrated that poststroke depression(PSD) may be related with the disequilibrium between noradrenaline and 5-hydroxytryptamine (5-HT) caused by cerebral injury. The injured regions involve noradrenergic and 5-hydroxytryptaminergic neurons as well as conduction pathway.The levels of noradrenaline and 5-HT would be decreased.OBJECTIVE: To observe the effect of fluoxetine on preventing against PSD and recovery of neurologic function, and analyze the relationship of fluoxetine and the 5-HT level.DESIGN: A randomized controlled clinical trial.SETTING: Department of Neurology, First Hospital Affiliated to Soochow University.PARTICIPANTS: Ninety consecutive patients, 47 female and 43 male, were recruited who admitted to hospital for recent stroke in the Department of Neurology, First Affiliated Hospital of Soochow University between September 2003 and February 2005. Subjects were aged (64±7) years, ranging from 47 to 79 years old. They all met the diagnosis criteria of various cerebrovascular diseases formulated in the 4th National Cerebrovascular Disease Conference and confirmed as stroke by skull CT or MRI; The time from onset to tentative administration was less than 7 days; The patients had clear consciousness, without obvious language disorder. They were randomized into treatment group (n =48) and placebo group (n =42).METHODS: ①All the patients were given routine treatment according to treatment guideline of cerebrovascular disease after admission. Patients in the treatment group and placebo group received 20 mg/d fluoxetine and placebo (component: vitamin C) for 8 weeks, respectively. ② Neurologic deficit was assessed according to 24-item Hamilton Rating Scale for Depression (HAMD) and Activity of Daily Living Scale (ADL) before and at 2,4 and 8 weeks after test, separately; Meanwhile, the levels of platelet 5-HT and plasma 5-HT were determined. Grading criteria of HAMD intergral depression: non-depression < 8 points

  12. Efficacy and safety of monotherapy with the novel sodium/glucose cotransporter-2 inhibitor tofogliflozin in Japanese patients with type 2 diabetes mellitus: a combined Phase 2 and 3 randomized, placebo-controlled, double-blind, parallel-group comparative study.

    Science.gov (United States)

    Kaku, Kohei; Watada, Hirotaka; Iwamoto, Yasuhiko; Utsunomiya, Kazunori; Terauchi, Yasuo; Tobe, Kazuyuki; Tanizawa, Yukio; Araki, Eiichi; Ueda, Masamichi; Suganami, Hideki; Watanabe, Daisuke

    2014-03-28

    In recent years, several oral antidiabetic drugs with new mechanisms of action have become available, expanding the number of treatment options. Sodium/glucose cotransporter-2 (SGLT2) inhibitors are a new class of oral antidiabetic drugs with an insulin-independent mechanism promoting urinary glucose excretion. We report the results of a combined Phase 2 and 3 clinical study (Japic CTI-101349) of the SGLT2 inhibitor tofogliflozin (CSG452, RG7201) in Japanese patients with type 2 diabetes mellitus. The efficacy and safety of tofogliflozin were assessed in this multicenter, placebo-controlled, randomized, double-blind parallel-group study involving 230 patients with type 2 diabetes mellitus with inadequate glycemic control on diet/exercise therapy. Between 30 October 2010 and 28 February 2012, patients at 33 centers were randomized to either placebo (n = 56) or tofogliflozin (10, 20, or 40 mg; n = 58 each) orally, once daily for 24 weeks. The primary efficacy endpoint was the change from baseline in HbA1c at week 24. Overall, 229 patients were included in the full analysis set (placebo: n = 56; tofogliflozin 10 mg: n = 57; tofogliflozin 20 and 40 mg: n = 58 each). The least squares (LS) mean change (95% confidence interval) from baseline in HbA1c at week 24 was -0.028% (-0.192 to 0.137) in the placebo group, compared with -0.797% (-0.960 to -0.634) in the tofogliflozin 10 mg group, -1.017% (-1.178 to -0.856) in the tofogliflozin 20 mg group, and -0.870% (-1.031 to -0.709) in the tofogliflozin 40 mg group (p Japanese patients with type 2 diabetes mellitus. Phase 3 studies were recently completed and support the findings of this combined Phase 2 and 3 study. This study was registered in the JAPIC clinical trials registry (ID: Japic CTI-101349).

  13. A placebo-controlled, double-blind comparison of clobazam and diazepam in the treatment of anxiety.

    Science.gov (United States)

    Jacobson, A F; Goldstein, B J; Dominguez, R A; Steinbook, R M

    1983-08-01

    In a randomized, placebo-controlled, double-blind study, the efficacy and safety of clobazam and diazepam were compared in 114 anxious outpatients. During the 4-week double-blind phase of the study, the mean daily dose was 59 mg for clobazam and 25 mg for diazepam. Results indicate statistically significant efficacy, measured by both patient and physician rating scales, for both active drugs compared to placebo. The incidence of sedation was similar for the two active treatment groups; dizziness was more frequent in the diazepam group.

  14. Early mortality of alcoholic hepatitis: A review of data from placebo-controlled clinical trials

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the early mortality of placebo-treated alcoholic hepatitis patients. METHODS: Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. RESULTS: A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infect...

  15. Antidepressant action of sulpiride. Results of a placebo-controlled double-blind trial.

    Science.gov (United States)

    Rüther, E; Degner, D; Munzel, U; Brunner, E; Lenhard, G; Biehl, J; Vögtle-Junkert, U

    1999-07-01

    The purpose of this multicenter, randomized, double-blind, placebo-controlled parallel-group comparative study was to prove the efficacy and tolerance of sulpiride (150-300 mg) against placebo in mild to moderate depressive syndrome. The primary criterion of efficacy was the course of the HAMD total score from day 1 to day 42, compared between the two treatment groups. The duration of the treatment was six weeks, preceded by a one-week placebo run-in phase. The HAMD, CGI and KUSTA scores were determined, the tolerance assessed, and the laboratory parameters and serum prolactin levels determined before, during and at the end of the trial. 177 outpatients aged from 18 to 70 years with mild to moderate depressive syndrome (ICD-10: F32.0, F32.1, F33.0, F33.1) and a score of 18-27 points on the 21-item HAMD scale were randomized, 171 of whom (sulpiride: n=83; placebo: n=88) were included in the intention-to-treat analysis. All the baseline data recorded for the two groups displayed comparable values. The decrease of the HAMD score between day 1 and day 42 yielded a difference of 2.5 points in favour of the sulpiride group. This difference is statistically significant (p = 0.0007). The evaluations of the cases treated for at least 14 days or for 42 days (per protocol) showed consistent values. The analysis of the CGI values showed similarly distinct and clinically relevant differences for sulpiride in comparison with placebo. The evaluation of the KUSTA scores yielded mostly comparable values for the two groups. Adverse events occurred with about the same type and frequency in both groups, with severe adverse events occurring only in two placebo patients. The laboratory parameters revealed no significant differences between the treatment groups, with the exception of prolactin which moderately exceeded the range of normal in 50% of the patients treated with sulpiride. This trial proved that sulpiride is effective and well-tolerated when given in a mean dose of 181 mg per

  16. The predictive value of the dexamethasone suppression test. A placebo-controlled study.

    Science.gov (United States)

    Peselow, E D; Stanley, M; Filippi, A M; Barouche, F; Goodnick, P; Fieve, R R

    1989-11-01

    We evaluated the dexamethasone suppression test (DST) as a predictor of response to drugs and placebo in 105 patients, in a large double-blind placebo-controlled out-patient trial to determine the efficacy of paroxetine HCl, a selective serotonin reuptake inhibitor, compared with that of imipramine HCl and placebo. The presence of a positive or negative DST did not predict response to either paroxetine or imipramine. However, a positive DST predicted a poorer response to placebo: only 3 out of 18 patients who showed DST non-suppression responded to placebo, as opposed to 11 out of 21 who exhibited DST suppression (P less than 0.05). A positive DST was associated with a 61% response to drugs and a 16% response to placebo. This finding suggests that the presence of a positive DST implies the need for active somatic treatment.

  17. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

  18. Impact of linaclotide treatment on work productivity and activity impairment in adults with irritable bowel syndrome with constipation: results from 2 randomized, double-blind, placebo-controlled phase 3 trials.

    Science.gov (United States)

    Buono, Jessica L; Tourkodimitris, Stavros; Sarocco, Phil; Johnston, Jeffrey M; Carson, Robyn T

    2014-08-01

    Irritable bowel syndrome with constipation (IBS-C), a chronic functional gastrointestinal disorder, has been shown to negatively affect work productivity and impair daily activity, resulting in a substantial burden for patients and employers. Linaclotide is a first-in-class guanylate cyclase-C agonist approved for the treatment of adults with IBS-C and chronic idiopathic constipation in the United States. To analyze the impact of treatment with linaclotide on work productivity and daily activity impairment in adults with IBS-C and estimate the indirect costs associated with this condition. This was a post-hoc analysis of data on IBS-C-related work time missed and work and activity impairment from 2 phase 3 clinical trials that assessed the efficacy and safety of linaclotide therapy in adults with IBS-C. The Work Productivity and Activity Impairment Questionnaire for IBS-C (WPAI:IBS-C) was self-administered at baseline and at weeks 4, 8, and 12 during the 12-week treatment periods in Trials 1 and 2 and at weeks 16, 20, and 26 during the extended treatment period in Trial 2. An analysis of covariance was conducted to assess changes from baseline to all study weeks for each WPAI:IBS-C measure. Indirect costs were calculated by converting overall work productivity losses into monetary values using the human capital cost approach. Of the 1602 patients with IBS-C who were randomized in the 2 clinical trials, 1555 (97.1%) completed a baseline and at least 1 postbaseline WPAI:IBS-C assessment and were included in the analysis cohort; 1148 (71.7%) of these patients were employed. Once-daily treatment with linaclotide significantly reduced overall work productivity loss and daily activity impairment among patients with IBS-C at all study weeks. From baseline to week 12, compared with placebo, linaclotide significantly reduced presenteeism by 5.2%, overall work productivity loss by 6.1%, and daily activity impairment by 4.7% (all P employee with IBS-C. The results of this

  19. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials

    Science.gov (United States)

    Kavanaugh, Arthur; Ritchlin, Christopher; Rahman, Proton; Puig, Lluis; Gottlieb, Alice B; Li, Shu; Wang, Yuhua; Noonan, Lenore; Brodmerkel, Carrie; Song, Michael; Mendelsohn, Alan M; McInnes, Iain B

    2014-01-01

    Objective Evaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA). Methods We conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study). Results Integrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0–24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p<0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 – wk 52, total vdH-S score mean change: 0.08). Conclusions Ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active Ps

  20. Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stéphanie J.E. Becker

    2014-09-01

     Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial. 

  1. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

  2. 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 ba

  3. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

  4. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis

    NARCIS (Netherlands)

    Bade, JJ; Nieuwenburg, A; vanderWeele, LT; Mensink, HJA

    1997-01-01

    Objective To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC). Patients and methods Twenty patients who fullfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10

  5. Influenza vaccination in children with asthma: randomized double-blind placebo- controlled trial.

    NARCIS (Netherlands)

    H.J. Bueving (Herman); R.M.D. Bernsen (Roos); J.C. de Jongste (Johan); L.W.A. van Suijlekom-Smit (Lisette); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert); M.P.M.H. Rutten-van Mölken (Maureen); S. Thomas (Siep); J.C. van der Wouden (Hans)

    2004-01-01

    textabstractThere is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination

  6. Retrospective quality control review of FDG scans in the imaging sub-study of PALETTE EORTC 62072/VEG110727: a randomized, double-blind, placebo-controlled phase III trial

    Energy Technology Data Exchange (ETDEWEB)

    Hristova, Ivalina [European Organization for Research and Treatment of Cancer Headquarters, Brussels (Belgium); Radboud University Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Boellaard, Ronald [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Vogel, Wouter [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Nuclear Medicine, Amsterdam (Netherlands); Mottaghy, Felix [Maastricht University, Department of Nuclear Medicine, Maastricht (Netherlands); Marreaud, Sandrine; Collette, Sandra [European Organization for Research and Treatment of Cancer Headquarters, Brussels (Belgium); Schoeffski, Patrick [University Hospitals Leuven, Department of General Medical Oncology, Leuven Cancer Institute, Department of Oncology, KU Leuven (Belgium); Sanfilippo, Roberta [Istituto Nazionale Tumori, Milano (Italy); Dewji, Raz [GlaxoSmithKline, Oncology R and D, Uxbridge (United Kingdom); Graaf, Winette van der [Radboud University Medical Centre, Department of Medical Oncology, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2015-05-01

    {sup 18}F-Labelled fluorodeoxyglucose (FDG) can detect early changes in tumour metabolism and may be a useful quantitative imaging biomarker (QIB) for prediction of disease stabilization, response and duration of progression-free survival (PFS). Standardization of imaging procedures is a prerequisite, especially in multicentre clinical trials. In this study we reviewed the quality of FDG scans and compliance with the imaging guideline (IG) in a phase III clinical trial. Forty-four cancer patients were enrolled in an imaging sub-study of a randomized international multicentre trial. FDG scan had to be performed at baseline and 10-14 days after treatment start. The image transmittal forms (ITFs) and Digital Imaging and Communications in Medicine (DICOM) [1] standard headers were analysed for compliance with the IG. Mean liver standardized uptake values (LSUV{sub mean}) were measured as recommended by positron emission tomography (PET) Response Criteria in Solid Tumors 1.0 (PERCIST) [2]. Of 88 scans, 81 were received (44 patients); 36 were properly anonymized; 77/81 serum glucose values submitted, all but one within the IG. In 35/44 patients both scans were of sufficient visual quality. In 22/70 ITFs the reported UT differed by >1 min from the DICOM headers (max. difference 1 h 4 min). Based on the DICOM, UT compliance for both scans was 31.4 %. LSUV{sub mean} was fairly constant for the 11 patients with UT compliance: 2.30 ± 0.33 at baseline and 2.27 ± 0.48 at follow-up (FU). Variability substantially increased for the subjects with unacceptable UT (11 patients): 2.27 ± 1.04 at baseline and 2.18 ± 0.83 at FU. The high attrition number of patients due to low compliance with the IG compromised the quantitative assessment of the predictive value for early response monitoring. This emphasizes the need for better regulated procedures in imaging departments, which may be achieved by education of involved personnel or efforts towards regulations. LSUV{sub mean} could be

  7. A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide

    Directory of Open Access Journals (Sweden)

    Wang Eunice S

    2012-11-01

    Full Text Available Abstract Background Lenalidomide treatment in myelodysplastic syndrome (MDS may lead to thrombocytopenia and dose reductions/delays. This study evaluated the safety and tolerability of the thrombopoietin mimetic romiplostim and its effects on the incidence of clinically significant thrombocytopenic events (CSTEs in lower risk MDS patients receiving lenalidomide. Methods Patients were assigned to weekly placebo (n = 12 or romiplostim 500 μg (n = 14 or 750 μg (n = 13 for four 28-day lenalidomide cycles. Results The treatment groups were generally similar with respect to baseline disease characteristics. Del(5q abnormalities were noted in 1 (8% patient in the placebo group, 3 (21% in the romiplostim 500 μg group, and two (15% in the 750 μg group. CSTEs were noted in 8 (67% patients in the placebo group, 4 (29% in the romiplostim 500 μg group, and 8 (62% in the romiplostim 750 μg group. Throughout the study, median platelet counts trended lower in placebo-treated than in romiplostim-treated patients. Thrombocytopenia-related adjustments in lenalidomide occurred in 6 (50% patients in the placebo group, 5 (36% in the romiplostim 500 μg group, and 2 (15% in the 750 μg group. Although the percentages of patients who received platelet transfusions were similar across treatment groups, there was a trend toward lower numbers of transfusions in both romiplostim groups during each treatment cycle. There were two serious treatment-related adverse events during the treatment period (cerebrovascular accident, placebo; worsening thrombocytopenia, romiplostim 500 μg. Two patients (romiplostim 500 and 750 μg, respectively had an increase in bone marrow blasts to >20% during treatment, but had no post-treatment biopsy to confirm or exclude the diagnosis of progression to AML. Conclusions These data suggest that romiplostim administered to MDS patients during lenalidomide treatment may decrease the frequency of dose

  8. 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.

  9. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder.

    Science.gov (United States)

    Septien-Velez, Lucia; Pitrosky, Bruno; Padmanabhan, Sudharshan Krishna; Germain, Jean-Michel; Tourian, Karen A

    2007-11-01

    The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.

  10. Otilonium bromide in irritable bowel syndrome: a dose-ranging randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Chmielewska-Wilkoń, Danuta; Reggiardo, Giorgio; Egan, Colin Gerard

    2014-09-14

    To examine the efficacy and safety of otilonium bromide (OB) in treatment-sensitive functional irritable bowel syndrome (IBS) clinical parameters. Ninety-three patients (44.8 ± 12.6 years, 69% female) with IBS symptoms complying with Rome II criteria participated in this double-blind, placebo-controlled, randomised, dose-ranging phase I/II study. Patients were administered OB 20 mg (n = 24), 40 mg (n = 23) and 80 mg (n = 23) tid or placebo (n = 23) in 4 parallel groups for 4 wk. Primary efficacy variables included abdominal discomfort, intestinal habits, number of daily evacuations and stool consistency. Secondary efficacy measures included return to regular intestinal habits and global discomfort. Safety was also assessed. Baseline clinical characteristics were similar among the 4 groups. Although individual parameters such as intensity and frequency of abdominal discomfort, bloating or pain were reduced by OB over the 4 wk, no significant differences were observed between groups. Similarly, no difference was observed between OB treatment or placebo for mucus in stool and incomplete or difficulty of evacuation. However, evacuation frequency was significantly reduced after 4 wk by 80 mg OB compared to placebo (-8.36% for placebo vs -41.9% for 80 mg OB, P < 0.01). While 21.7% of patients in the placebo group experienced regular intestinal habits after 4 wk, this improvement was greater for patients treated with 40 mg OB (P < 0.01 vs placebo). Furthermore, a dose-dependent reduction in frequency of diarrhoea (χ(2)-test for trend = 11.5, P < 0.001) and an increase in normal stool frequency was observed. Combining individual variables into a global discomfort index revealed significant improvement among increasing OB doses, favouring 40 mg (P = 0.013) and 80 mg OB (P = 0.001) over placebo. No difference was observed between frequency of adverse events for placebo vs OB. This dose-ranging study demonstrates that OB at 40 and 80 mg can improve individual and global

  11. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN® in 56-80-Year-Old Subjects.

    Directory of Open Access Journals (Sweden)

    Richard N Greenberg

    Full Text Available Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA was assessed in a 56-80 years old population.MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56-80 year old vaccinia-experienced subjects (N = 120. Subjects received either two injections of MVA (MM group or one injection of Placebo and one injection of MVA (PM group four weeks apart. Safety was evaluated by assessment of adverse events (AE, focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA and a plaque reduction neutralization test (PRNT before and at different time points after vaccination.Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4 were as follows: Seroconversion (SC rates (doubling of titers from baseline in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%], and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]. Geometric mean titers (GMT measured by ELISA two weeks after the final vaccination for

  12. A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects

    Science.gov (United States)

    Greenberg, Richard N.; Hay, Christine M.; Stapleton, Jack T.; Marbury, Thomas C.; Wagner, Eva; Kreitmeir, Eva; von Krempelhuber, Alfred; Young, Philip; Nichols, Richard; Meyer, Thomas P.; Weigl, Josef; Virgin, Garth; Arndtz-Wiedemann, Nathaly; Chaplin, Paul

    2016-01-01

    Background Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56–80 years old population. Methods MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Results Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after

  13. Randomized, double-blind, placebo-controled clinical trial of sublingual immunotherapy in natural rubber latex allergic patients

    Directory of Open Access Journals (Sweden)

    Audicana Maria T

    2011-08-01

    Full Text Available Abstract Background Natural rubber latex allergy is a common and unsolved health problem. Since the avoidance of exposure is very difficult, immunotherapy is strongly recommended, but before its use in patients, it is essential to prove the efficacy and safety of extracts. The aim of the present randomised, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of latex sublingual immunotherapy in adult patients undergoing permanent latex avoidance. Methods Twenty-eight adult latex-allergic patients (5 males and 23 females, with mean age of 39 years (range 24-57 were randomized to receive a commercial latex-sublingual immunotherapy or placebo during one year, followed by another year of open, active therapy. The following outcomes were measured at baseline and at the end of first and second year of follow-up: skin prick test, gloves-use score, conjunctival challenge test, total and specific IgE, basophil activation test, and adverse reactions monitoring. Results No significant difference in any of the efficacy in vivo variables was observed between active and placebo groups at the end of the placebo-controlled phase, nor when each group was compared with their baseline values at the end of the two year-study. An improvement in the average percentage of basophils activated was observed. During the induction phase, 4 reactions in the active group and 5 in the placebo group were recorded. During the maintenance phase, two patients dropped out due to pruritus and to acute dermatitis respectively. Conclusion Further studies are needed to evaluate latex-sublingual immunotherapy, since efficacy could not be demonstrated in adult patients with avoidance of the allergen. Trial registration number ACTRN12611000543987

  14. A Double-Blind Randomized Placebo-Controlled Clinical Trial of Squalamine Ointment for tinea capitis Treatment

    OpenAIRE

    2015-01-01

    International audience; Background Novel treatments against for tinea capitis are needed, and the natural aminosterol squal-amine is a potential topical antidermatophyte drug candidate. Objectives This phase II randomized double-blind placebo-controlled clinical trial aimed at testing the efficacy and safety of a three-week squalamine ointment regimen for the treatment of tinea capitis. Patients Males aged 6–15 years presenting with tinea capitis were treated with either topical squal-amine o...

  15. Influence of a Suggestive Placebo Intervention on Psychobiological Responses to Social Stress: A Randomized Controlled Trial.

    Science.gov (United States)

    Zimmermann-Viehoff, Frank; Steckhan, Nico; Meissner, Karin; Deter, Hans-Christian; Kirschbaum, Clemens

    2016-01-01

    We tested the hypothesis that a suggestive placebo intervention can reduce the subjective and neurobiological stress response to psychosocial stress. Fifty-four healthy male subjects with elevated levels of trait anxiety were randomly assigned in a 4:4:1 fashion to receive either no treatment (n = 24), a placebo pill (n = 24), or a herbal drug (n = 6) before undergoing a stress test. We repeatedly measured psychological variables as well as salivary cortisol, alpha-amylase, and heart rate variability prior to and following the stress test. The stressor increased subjective stress and anxiety, salivary cortisol, and alpha-amylase, and decreased heart rate variability (all P placebo or no treatment were found. Subjects receiving placebo showed increased wakefulness during the stress test compared with no-treatment controls (P placebo intervention increased alertness, but modulated neither subjective stress and anxiety nor the physiological response to psychosocial stress.

  16. Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial

    OpenAIRE

    Misra, Usha Kant; Kalita, Jayantee; Yadav, Rama Kant

    2007-01-01

    The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with

  17. Oral iloprost as a treatment for Raynaud's syndrome: a double blind multicentre placebo controlled study.

    Science.gov (United States)

    Belch, J J; Capell, H A; Cooke, E D; Kirby, J D; Lau, C S; Madhok, R; Murphy, E; Steinberg, M

    1995-01-01

    OBJECTIVE--To compare the efficacy, tolerance and safety of 50-150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud's syndrome. METHODS--The study was multicentre (n = 3), double blind and placebo controlled. Sixty three patients who had eight or more vasospastic attacks per week were enrolled. After a one week run-in period, all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days. Diary cards assessed the duration and severity of the vasospastic attacks. Side effects were monitored by direct questioning. A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later. RESULTS--Patient opinion tended to favour iloprost at the end of the 10 day treatment phase (p = 0.09) and this was significant at day 24 (the follow up visit) (p = 0.011). Although the duration and severity of attacks tended to decrease in the iloprost treated group, these results tended not to reach statistical significance (for severity p = 0.06 at end of treatment, p = 0.09 on day 24). CONCLUSION--Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud's syndrome associated with systemic sclerosis, but this route of administration is inconvenient. This study evaluated the use of iloprost administered orally to patients with Raynaud's syndrome. Patient documented improvement was significantly improved by iloprost. Diary card analysis showed a trend in favour of iloprost, but these results did not reach statistical significance. PMID:7538285

  18. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

    Science.gov (United States)

    Ritchlin, Christopher; Rahman, Proton; Kavanaugh, Arthur; McInnes, Iain B; Puig, Lluis; Li, Shu; Wang, Yuhua; Shen, Yaung-Kaung; Doyle, Mittie K; Mendelsohn, Alan M; Gottlieb, Alice B

    2014-01-01

    Objective Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse

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

    National Research Council Canada - National Science Library

    Huber, Matthias; Treutler, Till; Martus, Peter; Kurzidim, Antje; Kreutz, Reinhold; Beige, Joachim

    2013-01-01

    .... 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...

  20. Statin tolerability: In defence of placebo-controlled trials

    OpenAIRE

    Tobert, Jonathan A; Newman, Connie B.

    2015-01-01

    Background Statin intolerance is a barrier to effective lipid-lowering treatment. A significant number of patients stop prescribed statins, or can take only a reduced dose, because of adverse events attributed to the statin, and are then considered statin-intolerant. Methods Examination of differences between statin and placebo in withdrawal rates due to adverse events – a good measure of tolerability – in statin cardiovascular outcome trials in patients with advanced disease and complex medi...

  1. A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis.

    Science.gov (United States)

    Schwebke, Jane R; Morgan, Franklin G; Koltun, William; Nyirjesy, Paul

    2017-09-01

    A novel single oral dose granule formulation of secnidazole 2 g, a 5-nitroimidazole with a longer half-life (∼17 hours) than metronidazole (∼8 hours), is being developed to treat bacterial vaginosis. We sought to evaluate the effectiveness and safety of single-dose secnidazole 2 g compared to placebo for the treatment of women with bacterial vaginosis. In all, 189 women with bacterial vaginosis were randomized 2:1 to receive a single oral dose of secnidazole 2 g (N = 125) or matched placebo (N = 64) at 21 centers in the United States. The primary endpoint was the proportion of clinical outcome responders, defined as those with: (1) normal vaginal discharge; (2) negative 10% potassium hydroxide whiff test; and (3) vaginosis after treatment; (2) negative potassium hydroxide whiff tests; and (3) clue cells vaginosis, were consistent with the clinical outcome responder rate analysis (58.9% vs 24.6%; P vaginosis treatment (68.0% [68/100] vs 29.6% [16/54]; P vaginosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial

    Directory of Open Access Journals (Sweden)

    Roth T

    2015-01-01

    Full Text Available Thomas Roth,1 Tali Nir,2 Nava Zisapel2,3 1Henry Ford Sleep Disorders Center, Detroit, MI, USA; 2Neurim Pharmaceuticals Ltd, Tel Aviv, Israel; 3Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel Introduction: Melatonin, secreted by the pineal gland during the night phase, is a regulator of the biological clock and sleep tendency. Totally blind subjects frequently report severe, periodic sleep problems, with 50%–75% of cases displaying non-24-hour sleep–wake disorder (N24HSWD due to inability to synchronize with the environmental day–night cycle. Melatonin immediate-release preparations are reportedly effective in N24HSWD. Here, we studied the efficacy and safety of prolonged-release melatonin (PRM, a registered drug for insomnia, for sleep disorders in totally blind subjects living in normal social environments. The primary endpoint was demonstration of clinically meaningful effects on sleep duration (upper confidence interval [CI] limit >20 minutes whether significant or not to allow early decision-making on further drug development in this indication. Trial registration: ClinicalTrials.gov registry – NCT00972075. Methods: In a randomized, double-blind, placebo-controlled proof-of-principle study, 13 totally blind subjects had 2 weeks' placebo run-in, 6 weeks' randomized (1:1 PRM (Circadin® or placebo nightly, and 2 weeks' placebo run-out. Outcome measures included daily voice recorded sleep diary, Clinical Global Impression of Change (CGIC, WHO-Five Well-being Index (WHO-5, and safety. Results: Mean nightly sleep duration improved by 43 minutes in the PRM and 16 minutes in the placebo group (mean difference: 27 minutes, 95% CI: -14.4 to 69 minutes; P=0.18; effect size: 0.82 meeting the primary endpoint. Mean sleep latency decreased by 29 minutes with PRM over placebo (P=0.13; effect size: 0.92 and nap duration decreased in the PRM but not placebo group. The variability in sleep onset/offset and

  3. Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms.

    Science.gov (United States)

    Bouchard, P; Panay, N; de Villiers, T J; Vincendon, P; Bao, W; Cheng, R J; Constantine, G

    2012-02-01

    To evaluate the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) vs. tibolone and placebo for menopausal vasomotor symptoms and the incidence of uterine bleeding. This 12-week, double-blind, randomized, controlled trial was conducted at 35 sites in Europe, two sites in South Africa, and one site in Mexico. Postmenopausal women with ≥50 moderate or severe hot flushes per week (n = 485) were randomized to desvenlafaxine 100 mg/day, tibolone 2.5 mg/day, or placebo. Reduction in the average daily number of moderate and severe hot flushes at weeks 4 and 12 (primary endpoint) was evaluated using analysis of covariance. Safety assessments included incidence of uterine bleeding, adverse events, laboratory values, and vital signs. At week 12, no statistically significant difference was observed in reduction of the average daily number of moderate and severe hot flushes for desvenlafaxine (-5.78) vs. placebo (-5.82; p = 0.921), although time to 50% reduction was significantly less than placebo (13 vs. 26 days, p = 0.006). Hot flush reduction with tibolone (-8.21) was significantly greater than placebo (p desvenlafaxine, was generally mild to moderate, and resolved within the first 2 weeks. Significantly more subjects experienced bleeding with tibolone (23%) vs. desvenlafaxine (12%; p Desvenlafaxine did not separate from placebo in reducing the number of moderate to severe hot flushes at week 12, although it did allow women to achieve 50% reduction sooner than placebo. Tibolone did separate from placebo, but with smaller than expected effect. The placebo effect was high (57%). Adverse drug reactions were consistent with the known safety profile of desvenlafaxine, and significantly more women who received tibolone experienced episodes of bleeding compared with women who received desvenlafaxine or placebo.

  4. Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR trial [NCT00256139

    Directory of Open Access Journals (Sweden)

    Shumack Stephen

    2005-12-01

    Full Text Available Abstract Background Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG1 monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. Methods A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529 or placebo (n = 264 for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo. The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36 and Dermatology Life Quality Index (DLQI. Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA, a visual analog scale (VAS for itching, and the Patient's Global Psoriasis Assessment (PGPA. Results Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P P Conclusion A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating

  5. Daily Sodium Butyrate Enema for the Prevention of Radiation Proctitis in Prostate Cancer Patients Undergoing Radical Radiation Therapy: Results of a Multicenter Randomized Placebo-Controlled Dose-Finding Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Maggio, Angelo, E-mail: maggio.angelo@gmail.com [Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Magli, Alessandro [Department of Radiotherapy, Ospedale S. Maria della Misericordia, Udine (Italy); Rancati, Tiziana [Prostate Cancer Programme, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Fiorino, Claudio [Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Valvo, Francesca [Division of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Fellin, Giovanni [Department of Radiotherapy, Ospedale Santa Chiara, Trento (Italy); Ricardi, Umberto [University of Turin, Department of Oncology, Torino (Italy); Munoz, Fernando [Radiotherapy Unit, AO Città della Salute e della Scienza di Torino, Torino (Italy); Cosentino, Dorian; Cazzaniga, Luigi Franco [Ospedale S. Anna, Como (Italy); Valdagni, Riccardo [Prostate Cancer Programme, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Division of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Vavassori, Vittorio [Department of Radiotherapy, Ospedale di Circolo, Varese (Italy)

    2014-07-01

    Purpose: To evaluate the efficacy of sodium butyrate enemas (NABUREN) in prostate cancer radiation therapy (RT) in reducing the incidence, severity, and duration of acute RT-induced proctitis. Methods and Materials: 166 patients, randomly allocated to 1 of 4 groups (rectal sodium butyrate 1 g, 2 g, or 4 g daily or placebo), were treated with NABUREN during and 2 weeks after RT. The grade of proctitis was registered in a daily diary. The correlation between NABUREN and proctitis was investigated through χ{sup 2} statistics. The toxicity endpoints considered were as follows: total number of days with grade ≥1 proctitis (≥G1); total number of days with grade ≥2 proctitis (≥G2); ≥G1 and ≥G2 proctitis lasting at least 3 and 5 consecutive days starting from week 4 (≥G1+3d, ≥G2+3d); damaging effects of RT on rectal mucosa as measured by endoscopy. The relationship between endpoints and pretreatment morbidities, hormonal therapy, presence of diabetes or hypertension, abdominal surgery, or hemorrhoids was investigated by univariate analysis. Results: The patients were randomly allocated to the 4 arms. No difference in the distribution of comorbidities among the arms was observed (P>.09). The mean ≥G1 and ≥G2 proctitis were 7.8 and 4.9 for placebo and 8.9 and 4.7 for the NABUREN group, respectively. No favorable trend in reduction of incidence, severity, and duration of ≥G1 and ≥G2 proctitis was observed with NABUREN use. In univariate analysis, ≥G1+3d toxicity was found to be related to hemorrhoids (P=.008), and a slight correlation was found between ≥G2 proctitis and hormonal therapy (P=.06). The RT effects on rectal mucosa as based on endoscopic assessment were mainly related to diabetes (P<.01). Endoscopy data at 6 week showed no significant difference between the placebo and butyrate arms. The other investigated endpoints were not correlated with any of the clinical risk factors analyzed. Conclusion: There was no evidence of efficacy

  6. "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...... 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 (...

  7. 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

  8. Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week-112 Efficacy and Safety Results of the Open-Label Long-Term Extension of a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Bingham, Clifton O; Mendelsohn, Alan M; Kim, Lilianne; Xu, Zhenhua; Leu, Jocelyn; Han, Chenglong; Lo, Kim Hung; Westhovens, Rene; Weinblatt, Michael E

    2015-12-01

    To evaluate the safety, efficacy, pharmacokinetics, immunogenicity, and radiographic progression through 2 years of treatment with intravenous (IV) golimumab plus methotrexate (MTX) in an open-label extension of a phase III trial of patients with active rheumatoid arthritis (RA) despite MTX therapy. In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, 592 patients with active RA were randomized (2:1) to intravenous golimumab 2 mg/kg plus MTX (Group 1) or placebo plus MTX (Group 2) at weeks 0 and 4, then every 8 weeks thereafter; placebo patients crossed over to golimumab at week 16 (early escape) or week 24 (crossover). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology 20%, 50%, 70% (ACR20, ACR50, ACR70) response criteria, 28-joint count disease activity score using the C-reactive protein level (DAS28-CRP), physical function and quality of life measures, and changes in the modified Sharp/van der Heijde scores (SHS). Safety was monitored through week 112. In total, 486 patients (82.1%) continued treatment through week 100, and 68.1%, 43.8%, and 23.5% had an ACR20/50/70 response, respectively, at week 100. Clinical response and improvements in physical function and quality of life were generally maintained from week 24 through 2 years. Mean change from baseline to week 100 in SHS score was 0.74 in Group 1 and 2.10 in Group 2 (P = 0.005); progression from week 52 to week 100 was clinically insignificant in both groups. A total of 481 patients completed the safety followup through week 112; 79.1% had an adverse event, and 18.2% had a serious adverse event. Clinical response to IV golimumab plus MTX was maintained through week 100. Radiographic progression following golimumab treatment was clinically insignificant between week 52 and week 100. No unexpected adverse events occurred through week 112, and the safety profile was consistent with anti-tumor necrosis factor therapy. © 2015 The

  9. 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

  10. Sham device v inert pill: randomised controlled trial of two placebo treatments

    Science.gov (United States)

    Kaptchuk, Ted J; Stason, William B; Davis, Roger B; Legedza, Anna R T; Schnyer, Rosa N; Kerr, Catherine E; Stone, David A; Nam, Bong Hyun; Kirsch, Irving; Goldman, Rose H

    2006-01-01

    Objective To investigate whether a sham device (a validated sham acupuncture needle) has a greater placebo effect than an inert pill in patients with persistent arm pain. Design A single blind randomised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls. Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study. Setting Academic medical centre. Participants 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale. Interventions Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks. Main outcomemeasures Arm pain measured on a 10 point pain scale. Secondary outcomes were symptoms measured by the Levine symptom severity scale, function measured by Pransky's upper extremity function scale, and grip strength. Results Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups, but changes were not different between the groups (-0.14, 95% confidence interval -0.52 to 0.25, P = 0.49). Changes in severity scores for arm symptoms and grip strength were similar between groups, but arm function improved more in the placebo pill group (2.0, 0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group (-0.33 (-0.40 to -0.26) v -0.15 (-0.21 to -0.09), P = 0.0001) and on the symptom severity scale (-0.07 (-0.09 to -0.05) v -0.05 (-0.06 to -0.03), P = 0.02). Differences were not significant, however, on the function scale or for grip strength. Reported adverse effects were different in the two groups. Conclusions The sham device had greater

  11. Partial reinforcement, extinction, and placebo analgesia.

    Science.gov (United States)

    Au Yeung, Siu Tsin; Colagiuri, Ben; Lovibond, Peter F; Colloca, Luana

    2014-06-01

    Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electrocutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both CRF and PRF produced placebo analgesia, with the magnitude of initial analgesia being larger after CRF. However, although the placebo analgesia established under CRF extinguished during test phase, the placebo analgesia established under PRF did not. These findings indicate that PRF can induce placebo analgesia and that these effects are more resistant to extinction than those established via CRF. PRF may therefore reflect a novel way of enhancing clinical outcomes via the placebo effect.

  12. Minimal dose interferon suppository treatment suppresses viral replication with platelet counts and serum albumin levels increased in chronically hepatitis C virus-infected patients: a phase 1b, placebo-controlled, randomized study.

    Science.gov (United States)

    Haruna, Yoshimichi; Inoue, Atsuo

    2014-02-01

    Animal studies have shown that rectally administrated interferon (IFN) is transferred into the lymphatic system via the rectal mucous membrane, suggesting that an IFN suppository could serve as another drug delivery method. We developed an IFN suppository and administered it to patients with chronic hepatitis C to evaluate its efficacy and safety. Twenty-eight patients with chronic hepatitis C participated in the study. The low-dose IFN suppository containing 1,000 international units (IU) of lymphoblastoid IFNα was administered to 14 patients daily for 24 weeks. Others had a placebo dosing. In 13 of the 14 IFN suppository-treated patients, viral load decreased at week 4. The serum hepatitis C virus (HCV) RNA levels (Log IU/mL, mean±standard error) were 5.65±0.18 before the treatment and 5.17±0.27 at week 4 (P=0.01). The 2'-5' oligoadenylate synthetase activity increased, while the CD4/CD8 ratio decreased significantly. Interestingly, platelet counts and serum albumin levels were significantly increased during and after the treatment. No serious adverse events were observed. The low-dose IFN suppository treatment suppressed HCV replication, modifying host immunity, with increased platelet counts and serum albumin levels. The IFN suppository could be considered a new drug delivery method to preserve the quality of life of patients.

  13. [Ethyl chloride aerosol spray for local anesthesia before arterial puncture: randomized placebo-controlled trial].

    Science.gov (United States)

    Ballesteros-Peña, Sendoa; Fernández-Aedo, Irrintzi; Vallejo-De la Hoz, Gorka

    2017-06-01

    To compare the efficacy of an ethyl chloride aerosol spray to a placebo spray applied in the emergency department to the skin to reduce pain from arterial puncture for blood gas analysis. Single-blind, randomized placebo-controlled trial in an emergency department of Hospital de Basurto in Bilbao, Spain. We included 126 patients for whom arterial blood gas analysis had been ordered. They were randomly assigned to receive application of the experimental ethyl chloride spray (n=66) or a placebo aerosol spray of a solution of alcohol in water (n=60). The assigned spray was applied just before arterial puncture. The main outcome variable was pain intensity reported on an 11-point numeric rating scale. The median (interquartile range) pain level was 2 (1-5) in the experimental arm and 2 (1-4.5) in the placebo arm (P=.72). Topical application of an ethyl chloride spray did not reduce pain caused by arterial puncture.

  14. Homoeopathy for delayed onset muscle soreness: a randomised double blind placebo controlled trial.

    Science.gov (United States)

    Vickers, A J; Fisher, P; Smith, C; Wyllie, S E; Lewith, G T

    1997-01-01

    OBJECTIVE: To pilot a model for determining whether a homoeopathic medicine is superior to placebo for delayed onset muscle soreness (DOMS). DESIGN: Randomised double blind placebo controlled trial. SETTING: Physiotherapy department of a homoeopathic hospital. SUBJECTS: Sixty eight healthy volunteers (average age 30; 41% men) undertook a 10 minute period of bench stepping carrying a small weight and were randomised to a homoeopathic medicine or placebo. OUTCOME MEASURES: Mean muscle soreness in the five day period after the exercise test, symptom free days, maximum soreness score, days to no soreness, days on medication. RESULTS: The difference between group means was 0.17 in favour of placebo with 95% confidence intervals +/- 0.50. Similar results were found for other outcome measures. CONCLUSION: The study did not find benefit of the homoeopathic remedy in DOMS. Bench stepping may not be an appropriate model to evaluate the effects of a treatment on DOMS because of wide variation between subject soreness scores. PMID:9429007

  15. Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Christensen, Jakob; Petrenaite, Vaiva; Attermann, Jørn

    2007-01-01

    and taking combination-type oral contraceptives, were randomized to treatment with placebo or a standard combination-type contraceptive pill. The dose-corrected trough plasma concentration of LTG and the ratio of N-2-glucuronide/unchanged LTG on urine after 21 days of concomitant placebo treatment...... was analyzed versus those after 21 days of concomitant treatment with the oral contraceptive pill. RESULTS: The mean dose-corrected LTG concentration after placebo treatment was 84%[95% confidence interval (CI), 45-134%] higher than after oral contraceptives, signifying an almost doubling of the concentration......PURPOSE: This study evaluates the effect of oral contraceptives on lamotrigine (LTG) plasma concentrations and urine excretion of LTG metabolites in a double-blind, placebo-controlled, crossover study in patients with epilepsy. METHODS: Women with epilepsy, treated with LTG in monotherapy...

  16. Randomized placebo-controlled crossover trial of tadalafil in Raynaud's phenomenon secondary to systemic sclerosis.

    Science.gov (United States)

    Schiopu, Elena; Hsu, Vivien M; Impens, Ann J; Rothman, Jennifer A; McCloskey, Deborah A; Wilson, Julianne E; Phillips, Kristine; Seibold, James R

    2009-10-01

    Raynaud's phenomenon (RP) is an important clinical feature of systemic sclerosis (SSc) for which consistently effective therapies are lacking. The study was designed to assess the safety, tolerability, and efficacy of tadalafil, a selective, long acting type V cyclic GMP phosphodiesterase (PDE-5) inhibitor, in this clinical syndrome. We performed a prospective, randomized, double-blind, placebo-controlled, crossover study comparing oral tadalafil at a fixed dose of 20 mg daily for a period of 4 weeks versus placebo in women with RP secondary to SSc. Thirty-nine subjects completed the study and were evaluable. There were no statistically significant differences in Raynaud Condition Score (RCS), frequency of RP episodes, or duration of RP episodes between treatment groups. Placebo response was a confounding factor. Tadalafil was well tolerated. Tadalafil appears to be safe and well tolerated but lacks efficacy in comparison to placebo as a treatment for RP secondary to SSc.

  17. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults.

    Directory of Open Access Journals (Sweden)

    Juliet Mpendo

    Full Text Available Strategies to enhance the immunogenicity of DNA vaccines in humans include i co-administration of molecular adjuvants, ii intramuscular administration followed by in vivo electroporation (IM/EP and/or iii boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study.Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG plasmid DNA (pDNA vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12 (GENEVAX IL-12 given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM.All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs were reported. T cell and antibody response rates after HIVMAG (x3 prime-Ad35 (x1 boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ ELISPOT responses was highest after HIVMAG (x3 without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3 prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected.The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected.ClinicalTrials.gov NCT01496989.

  18. ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

    National Research Council Canada - National Science Library

    Bruce E. Johnson; Fairooz Kabbinavar; Louis Fehrenbacher; John Hainsworth; Saifuddin Kasubhai; Bruce Kressel; Chin-Yu Lin; Thomas Marsland; Taral Patel; Jonathan Polikoff; Mark Rubin; Leonard White; James Chih-Hsin Yang; Chris Bowden; Vincent Miller

    2013-01-01

    This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non-small-cell lung cancer (NSCLC...

  19. Challenges and recommendations for placebo controls in randomized trials in physical and rehabilitation medicine: a report of the international placebo symposium working group.

    Science.gov (United States)

    Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

    2010-02-01

    Compared with other specialties, the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments. The best way to change this disadvantage is through a well conducted clinical research, such as standard placebo- or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in physical and rehabilitation medicine that ultimately translates to better clinical care. To address the challenges for the use of placebo in physical and rehabilitation medicine and randomized clinical trials and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in physical and rehabilitation medicine, (2) challenges for the use of placebo in physical and rehabilitation medicine, (3) bioethics, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group.

  20. Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Klaus Reither

    Full Text Available Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1 formulated with the adjuvant IC31, was evaluated in HIV-infected adults.HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay.47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015. Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells.H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response.Pan African Clinical Trials Registry (PACTR PACTR201105000289276.

  1. Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of advanced non-small-cell lung cancer (ATLAS).

    Science.gov (United States)

    Kabbinavar, Fairooz; Fehrenbacher, Louis; Hainsworth, John; Kasubhai, Saifuddin; Kressel, Bruce; Marsland, Thomas; Patel, Taral; Rubin, Mark; White, Leonard; Yang, James Chih-Hsin; Klughammer, Barbara; Colburn, Dawn; Miller, Vincent; Johnson, Bruce E

    2014-09-01

    ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified biomarkers were prospectively evaluated. Tumor samples were analyzed for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry [IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3). Progression-free survival (PFS) and overall survival (OS) were estimated. Of 743 patients randomized to receive maintenance treatment (after four cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7 months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99), which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS mutation status were not predictive of outcome. B+E-treated patients with EGFR mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR, 0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485-0.914; p = 0.0105). No OS benefit of B+E was observed. Patients with KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E. However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly predictive of survival. A larger sample size would be needed to confirm the initial trends observed in this study.

  2. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Astrup, Arne; Madsbad, Sten; Breum, Leif

    2008-01-01

    BACKGROUND: Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet and placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline......, dopamine, and serotonin-in patients with obesity. METHODS: We undertook a phase II, randomised, double-blind, placebo-controlled trial in five Danish obesity management centres. After a 2 week run-in phase, 203 obese patients (body-mass index 30-...

  3. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design.

    Science.gov (United States)

    Chiron, Catherine; Tonnelier, Sylvie; Rey, Elisabeth; Brunet, Marie-Lucie; Tran, Agnes; d'Athis, Philippe; Vincent, Jean; Dulac, Olivier; Pons, Gerard

    2006-06-01

    Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.

  4. 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.

  5. 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.

  6. Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan: a double-blind, randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Beyrer Julie

    2008-01-01

    Full Text Available Abstract Background This manuscript compares the efficacy and safety of duloxetine with placebo in Taiwanese women with SUI. Methods Taiwanese women with SUI were were randomly assigned to placebo (n = 61 or duloxetine 80 mg/day (n = 60 in this double-blind, 8-week, placebo-controlled study. Outcome variables included: incontinence episode frequency (IEF, Incontinence Quality of Life questionnaire (I-QOL scores, and Patient Global Impression of Improvement rating (PGI-I. Results Decrease in IEF was significantly greater in duloxetine-treated than placebo-treated women (69.98% vs 42.56%, P Conclusion Data provide evidence for the safety and efficacy of duloxetine for the treatment for Taiwanese women with SUI. Trial Registration ClinicalTrials.gov Identifier: NCT00475358

  7. The Deferasirox–AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial

    Science.gov (United States)

    Spellberg, Brad; Ibrahim, Ashraf S.; Chin-Hong, Peter V.; Kontoyiannis, Dimitrios P.; Morris, Michele I.; Perfect, John R.; Fredricks, David; Brass, Eric P.

    2012-01-01

    Objectives Host iron availability is fundamental to mucormycosis pathogenesis. The combination of liposomal amphotericin B (LAmB) and deferasirox iron chelation therapy synergistically improved survival in diabetic mice with mucormycosis. To determine the safety of combination deferasirox plus LAmB therapy for mucormycosis, a multicentred, placebo-controlled, double-blinded clinical trial was conducted. Methods Twenty patients with proven or probable mucormycosis were randomized to receive treatment with LAmB plus deferasirox (20 mg/kg/day for 14 days) or LAmB plus placebo (NCT00419770, clinicaltrials.gov). The primary analyses were for safety and exploratory efficacy. Results Patients in the deferasirox arm (n = 11) were more likely than those in the placebo arm (n = 9) to have active malignancy, neutropenia and corticosteroid therapy, and were less likely to receive concurrent non-study antifungal therapy. Reported adverse events and serious adverse events were similar between the groups. However, death was more frequent in the deferasirox than in the placebo arm at 30 days (45% versus 11%, P = 0.1) and 90 days (82% versus 22%, P = 0.01). Global success (alive, clinically stable, radiographically improved) for the deferasirox arm versus the placebo arm at 30 and 90 days, respectively, was 18% (2/11) versus 67% (6/9) (P = 0.06) and 18% (2/11) versus 56% (5/9) (P = 0.2). Conclusions Patients with mucormycosis treated with deferasirox had a higher mortality rate at 90 days. Population imbalances in this small Phase II study make generalizable conclusions difficult. Nevertheless, these data do not support a role for initial, adjunctive deferasirox therapy for mucormycosis. PMID:21937481

  8. 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 week

  9. Correction of Abdominal Distention by Biofeedback-Guided Control of Abdominothoracic Muscular Activity in a Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Barba, Elizabeth; Accarino, Anna; Azpiroz, Fernando

    2017-07-11

    Abdominal distention is produced by abnormal somatic postural tone. We developed an original biofeedback technique based on electromyography-guided control of abdominothoracic muscular activity. We performed a randomized, placebo-controlled study to demonstrate the superiority of biofeedback to placebo for the treatment of abdominal distention. At a referral center in Spain, we enrolled consecutive patients with visible abdominal distention who fulfilled the Rome III criteria for functional intestinal disorders (47 women, 1 man; 21-74 years old); 2 patients assigned to the placebo group withdrew and 2 patients assigned to biofeedback were not valid for analysis. Abdominothoracic muscle activity was recorded by electromyography. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas patients in the placebo received no instructions and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. The primary outcomes were subjective sensation of abdominal distention, measured by graphic rating scales for 10 consecutive days before and after the intervention. Patients in the biofeedback group effectively learned to reduce intercostal activity (by a mean 45% ± 3%), but not patients in the placebo group (reduced by a mean 5% ± 2%; P corrected by biofeedback-guided control of abdominothoracic muscular activity, compared with placebo. ClincialTrials.gov no: NCT01205100. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. 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 suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (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.

  11. Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

    Directory of Open Access Journals (Sweden)

    Dollinger Matthias M

    2010-08-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12 were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS, time to progression (TTP, tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6] or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]. Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365.

  12. Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Diener, Hans-Christoph; Agosti, Reto; Allais, Gianni; Bergmans, Paul; Bussone, Gennaro; Davies, Brendan; Ertas, Mustafa; Lanteri-Minet, Michel; Reuter, Uwe; Sánchez Del Río, Margarita; Schoenen, Jean; Schwalen, Susanne; van Oene, Joop

    2007-12-01

    Use of preventive therapy for migraine is often recommended for only 6-9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4-8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50-200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. 559 patients (68.3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; plife, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups. Sustained benefit was reported after discontinuation of topiramate, although number of migraine days did increase. These findings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients.

  13. Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome

    Science.gov (United States)

    Kaptchuk, Ted J.; Friedlander, Elizabeth; Kelley, John M.; Sanchez, M. Norma; Kokkotou, Efi; Singer, Joyce P.; Kowalczykowski, Magda; Miller, Franklin G.; Kirsch, Irving; Lembo, Anthony J.

    2010-01-01

    Background Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Methods Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL). Findings Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs. 4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with

  14. Placebos without deception: a randomized controlled trial in irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Ted J Kaptchuk

    Full Text Available BACKGROUND: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS. METHODS: Two-group, randomized, controlled three week trial (August 2009-April 2010 conducted at a single academic center, involving 80 primarily female (70% patients, mean age 47 ± 18 with IBS diagnosed by Rome III criteria and with a score ≥ 150 on the IBS Symptom Severity Scale (IBS-SSS. Patients were randomized to either open-label placebo pills presented as "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes" or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS. Secondary measures were IBS Symptom Severity Scale (IBS-SSS, IBS Adequate Relief (IBS-AR and IBS Quality of Life (IBS-QoL. FINDINGS: Open-label placebo produced significantly higher mean (±SD global improvement scores (IBS-GIS at both 11-day midpoint (5.2 ± 1.0 vs. 4.0 ± 1.1, p<.001 and at 21-day endpoint (5.0 ± 1.5 vs. 3.9 ± 1.3, p = .002. Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03 and adequate relief (IBS-AR, p = .02 and p = .03; and a trend favoring open-label placebo was observed for quality of life (IBS-QoL at the 21-day endpoint (p = .08. CONCLUSION: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with

  15. High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial.

    Science.gov (United States)

    Müller, Christian A; Geisel, Olga; Pelz, Patricia; Higl, Verena; Krüger, Josephine; Stickel, Anna; Beck, Anne; Wernecke, Klaus-Dieter; Hellweg, Rainer; Heinz, Andreas

    2015-08-01

    Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence.

  16. Methylphenidate for treating tobacco dependence in non-attention deficit hyperactivity disorder smokers: A pilot randomized placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Croghan Ivana T

    2011-01-01

    Full Text Available Abstract Background Methylphenidate blocks the re-uptake of dopamine by binding to the dopamine transporter in the presynaptic cell membrane and increases extracellular dopamine levels. Similarities in neuropsychologic effects between nicotine and methylphenidate make it an intriguing potential therapeutic option. Previous research of methylphenidate in smokers has suggested a possible beneficial effect for the relief of nicotine withdrawal symptoms, but showed no efficacy in helping smokers with attention deficit hyperactivity disorder (ADHD to stop smoking. Methods To investigate potential efficacy for relieving nicotine withdrawal symptoms and promoting smoking abstinence, we conducted a randomized, double-blind, placebo-controlled, phase II study of once-a-day osmotic-release oral system methylphenidate (OROS-MPH, Concerta® at a target dose of 54-mg/day for 8 weeks compared with placebo in 80 adult cigarette smokers. Results Of the 80 randomized subjects and median smoking rate was 20 cigarettes per day. At the end of the medication phase, the biochemically confirmed 7-day point prevalence smoking abstinence was 10% (4/40 for the placebo group and 2.5% (1/40 for the OROS-MPH group. Nicotine withdrawal was not found to differ significantly between treatment groups during the first 14 days following the start of medication prior to the target quit date (p = 0.464 or during the first 14 days following the target quit date (p = 0.786. Conclusion We observed no evidence of efficacy of OROS-MPH to aid smokers to stop smoking. Although there are biologically plausible hypotheses that support the use of OROS-MPH for treating tobacco dependence, we found no evidence to support such hypotheses. In addition to no increase in smoking abstinence, we saw no effect of OROS-MPH for tobacco withdrawal symptom relief and no change in smoking rates was observed in the OROS-MPH group compared to the placebo group.

  17. A Randomized, Placebo-Controlled Trial of D-Cycloserine for the Enhancementof Social Skills Training in Pervasive Developmental Disorders

    Science.gov (United States)

    2015-11-01

    AWARD NUMBER: W81XWH-09-1-0091 TITLE: A Randomized, Placebo -Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in...YYYY) November 2015 2. REPORT TYPE Final Report 3. DATES COVERED (From - To) 1Mar2009 - 31Aug2015 4. TITLE AND SUBTITLE A Randomized, Placebo ...treatment of social impairment in 68 children and young adolescents (ages 5-11 years) with ASDs during a randomized placebo -controlled trial. The

  18. Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF) : a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study

    NARCIS (Netherlands)

    Teerlink, John R.; Metra, Marco; Felker, G. Michael; Ponikowski, Piotr; Voors, Adriaan A.; Weatherley, Beth Davison; Marmor, Alon; Katz, Amos; Grzybowski, Jacek; Unemori, Elaine; Teichman, Sam L.; Cotter, Gad

    2009-01-01

    Background Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on sym

  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. 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.

  1. Mirtazapine in essential tremor: a double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Pahwa, Rajesh; Lyons, Kelly E

    2003-05-01

    We sought to determine whether mirtazapine is safe and well-tolerated as a treatment for essential tremor (ET). We studied mirtazapine in a randomized, double-blind, placebo-controlled, crossover study of 17 ET patients. Patients were started with 15 mg per day of either mirtazapine or placebo for 1 week and the dose was escalated weekly until the targeted dose of 45 mg per day was achieved. This dose was maintained for 2 weeks. Tremor was assessed at baseline and after 14 days of 45 mg of mirtazapine or placebo. There was a minimum washout period of 14 days between the two arms of the study. Tremor assessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire-39. Patient global improvement ratings indicated that in the placebo condition 12 patients were unchanged and 1 patient was mildly improved. In the mirtazapine condition, 10 patients were unchanged, 2 were moderately improved and 1 was markedly improved. There was no significant improvement with mirtazapine or placebo compared to baseline as measured by the Tremor Rating Scale. Adverse effects were more common in the mirtazapine group and included drowsiness, confusion, dry mouth, weight gain, polyuria, itching, nausea, gait and balance problems, blurred vision, and bad taste. We conclude that the majority of the ET patients do not benefit from mirtazapine. Mirtazapine has significant adverse effects and should be used cautiously in ET patients.

  2. Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure.

    Science.gov (United States)

    Sanders, Nichole C; Mancino, Michael J; Gentry, W Brooks; Guise, J Benjamin; Bickel, Warren K; Thostenson, Jeff; Oliveto, Alison H

    2013-08-01

    This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-week, double-blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during Week 1, were randomized and inducted onto gabapentin or placebo during Week 2, underwent a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years) participated in the detoxification portion of the study (gabapentin, n = 11; placebo, n = 13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a Drug × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.

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

    OpenAIRE

    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. De...

  4. Randomised, double-blind, placebo-controlled study of pivagabine in neurasthenia.

    Science.gov (United States)

    Pizzolato, G; Cagnin, A; Mancia, D; Caffarra, P; Avanzi, S; Copelli, S; Ciappina, C; Lo Presti, F; Spilimbergo, P G; D'Antonio, E; Di Costanzo, E; Matrango, M; Pastres, P; Urbani, P P; Signorino, M; Simoncelli, M; Provinciali, L; Regnicolo, L; Albano, C; Roccatagliata, G; Rubino, V; Cultrera, S; Fracassi, M

    1997-11-01

    One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.

  5. 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...

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

    Science.gov (United States)

    Walters, Elizabeth R; Lesk, Valerie E

    2016-01-01

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

  7. Working memory training in young children with ADHD: a randomized placebo-controlled trial

    NARCIS (Netherlands)

    Dongen-Boomsma, M. van; Vollebregt, M.A.; Buitelaar, J.; Slaats-Willemse, D.I.E.

    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

  8. Mycophenolate mofetil in renal transplantation : 3-year results from the placebo-controlled trial

    NARCIS (Netherlands)

    Behrend, M; Grinyo, J; Vanrenterghem, Y; Rodicio, J; Albrechtsen, D; Sadek, S; Soulillou, JP; van Son, W; Groth, C; Mjornstedt, L; Wiesel, M; Neumayer, HH; Tufveson, G; Ekberg, H; Tarantino, A; Thiel, G; Hene, R; Morgan, A; Ramos, E; Rees, M

    1999-01-01

    Background. The European double-blind, placebo (PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of acu

  9. 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).

  10. 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

  11. Working memory training in young children with ADHD: a randomized placebo-controlled trial

    NARCIS (Netherlands)

    Dongen-Boomsma, M. van; Vollebregt, M.A.; Buitelaar, J.; Slaats-Willemse, D.I.E.

    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

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

    NARCIS (Netherlands)

    Nourbakhsh, Mohammad Reza; Fearon, Frank J.

    2008-01-01

    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 Stat

  13. 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.

  14. 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…

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

    NARCIS (Netherlands)

    denBoer, JA; Westenberg, HGM; Pian, KLH

    1997-01-01

    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

  16. Effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis: a placebo-controlled multicenter trial.

    NARCIS (Netherlands)

    Rooij, J.G.M. van; Rijneveld, W.J.; Remeijer, L.; Volker-Dieben, H.J.; Eggink, C.A.; Geerards, A.J.; Mulder, P.G.H.; Doornenbal, P.; Beekhuis, W.H.

    2003-01-01

    OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities

  17. 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

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  19. Melatonin for Chronic Insomnia in Angelman Syndrome: A Randomized Placebo-Controlled Trial

    NARCIS (Netherlands)

    Braam, W.J.; Didden, H.C.M.; Smits, M.G.; Curfs, L.M.G

    2008-01-01

    Previous studies suggested that melatonin improves sleep in insomniac patients with Angelman syndrome. To assess the efficacy of melatonin, a randomized placebo-controlled study was conducted in 8 children with Angelman syndrome with idiopathic chronic insomnia. After a 1-week baseline period, patie

  20. A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD

    Science.gov (United States)

    2013-08-01

    New York, Biometrics Research Department, New York State Psychiatric Institute, 1996 17. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ...results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 2001; 62:860–868 31. Marshall RD, Beebe KL, Oldham M, Zaninelli R: Efficacy and

  1. 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

    2017-09-06

    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

  2. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Luc Dupuis

    Full Text Available BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS. METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio. The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48. Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.

  3. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

    DEFF Research Database (Denmark)

    Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

    2010-01-01

    This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

  4. Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

    NARCIS (Netherlands)

    de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

    Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

  5. Intravenous Immunoglobulin Treatment of Recurrent Miscarriage: an Update of Placebo-controlled Trials

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Background Immunological disturbances which may be treated with intravenous im-munoglobulin (IvIg) play a significant role in the majority of patients with recurrentmiscarriage (RM). The present study aimed to review the current knowledge aboutIvIg treatment in RM primarily based on results from published placebo-controlled tri-als. Seven placebo-controlled trials were identified comprising a total of 343 patients.The background variables, the treatment protocols and the results were extremely dif-ferent between the trials. Among the patients with secondary RM, a meta-analysisshowed that the pooled odds ratio for live birth among IvIg treated women comparedwith women infused with placebo was 1. 69 (95 % CI = 0. 72~ 3. 96, notsignificant). IvIg also seemed to be efficacious in patients with repeated secondtrimester intrauterine fetal deaths. A new big placebo-controlled trial should be con-ducted which focus on RM patients with secondary RM or recurrent second trimesterfetal deaths. Sufficient IvIg doses should be given with optimal time intervals.

  6. Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain – a randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Blahova Z

    2016-12-01

    Full Text Available Zuzana Blahova,1 Janina Claudia Holm,1 Thomas Weiser,2 Erika Richter,2 Matthias Trampisch,2 Elena Akarachkova3 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background/objective: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC of nonivamide (a capsaicinoid and nicoboxil (a nicotinic acid ester cream in the treatment of acute nonspecific low back pain.Materials and methods: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1.08%/nonivamide 0.17% (Finalgon® cream in treatment of acute nonspecific low back pain with the endpoints: pain intensity (PI difference between pre-dose baseline and 8 hours after first application and the end of treatment, mobility score, and efficacy score.Results: Patients (n=138, 21–65 years of age, were treated for up to 4 days with FDC or placebo cream. Mean baseline PI was 6.8 on a 0–10 point numerical rating scale. After 8 hours, pain was more reduced with the FDC than with placebo (adjusted means: 2.824 vs. 0.975 points; p<0.0001. On the last treatment day, mean pain reduction by the FDC was stronger than with placebo (adjusted means: 5.132 vs. 2.174 points; p<0.0001. Mobility on Day 1 was in favor of the FDC when compared to placebo (odds ratio [95% confidence interval {CI}]: 7.200 [3.609, 14.363], p<0.0001. At the end of treatment, patients treated with the FDC rated efficacy significantly higher than placebo (odds ratio [95% CI]: 11.370 [5.342, 24.199], p<0.0001. Both treatments were tolerated well. No serious adverse events were reported.Conclusion: Nicoboxil

  7. 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.

  8. Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Tania Cursino de Menezes Couceiro

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

  9. Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials.

    Science.gov (United States)

    Lebel, M H; Freij, B J; Syrogiannopoulos, G A; Chrane, D F; Hoyt, M J; Stewart, S M; Kennard, B D; Olsen, K D; McCracken, G H

    1988-10-13

    We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.

  10. Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebo-controlled studies.

    Science.gov (United States)

    Baker, David; Eisen, Drore

    2003-03-01

    The oral antiviral valacyclovir, which is 3 to 5 times more bioavailable than its parent compound acyclovir, is a good candidate for effective therapy to suppress recurrent herpes labialis lesions. The efficacy of oral valacyclovir in the suppression of herpes labialis has not previously been reported. Two identical, randomized, double-blind, parallel-group studies were conducted to evaluate the efficacy of oral valacyclovir 500 mg (n=49) versus placebo (n=49) once daily for 16 weeks in the suppression of herpes labialis among patients with a history of 4 or more recurrent lesions in the previous year. Data from the studies were pooled for analysis. Twenty-eight patients (60%) in the valacyclovir group compared with only 18 patients (38%) in the placebo group were recurrence-free throughout the 4-month treatment period (P=.041). The mean time to first recurrence was significantly longer with valacyclovir (13.1 weeks) compared with placebo (9.6 weeks) (P=.016). The total number of recurrences in patients using valacyclovir was 24 compared with 41 in patients using placebo. The incidence of adverse events during the 4-month treatment period was slightly lower in the valacyclovir group (22 events, 33% of patients) compared with the placebo group (29 events, 39% of patients). The results of these small double-blind, placebo-controlled studies suggest that oral valacyclovir 500 mg once daily for 4 months is effective and well tolerated for the prevention of recurrent herpes labialis. More research with larger patient numbers is warranted to corroborate and extend these findings.

  11. Safety and Efficacy of Methylphenidate for Apathy in Alzheimer's Disease: A Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Rosenberg, Paul B.; Lanctôt, Krista L.; Drye, Lea T.; Herrmann, Nathan; Scherer, Roberta W.; Bachman, David L.; Mintzer, Jacobo E.

    2014-01-01

    Objective In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Alzheimer's Disease Methylphenidate Trial (ADMET). Method Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety. Results 60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks' treatment, mean (SD) change in AES score was −1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group. Conclusions Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease. PMID:24021498

  12. The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials

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    Papadopoulos George

    2007-10-01

    Full Text Available Abstract Background Topiramate is approved for the prophylaxis (prevention of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ scores versus placebo (p Methods Mean MSQ and Medical Outcome Study Short Form 36 (SF-36 change scores (baseline to each double-blind assessment point were calculated for pooled intent-to-treat (ITT patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: Results Of 756 patients (mean age 39.8 years, 86% female, 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p Conclusion Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a ≥ 50% migraine frequency reduction.

  13. Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

    Science.gov (United States)

    Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

    2015-01-01

    Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

  14. An Analysis of Relapse Rates and Predictors of Relapse in 2 Randomized, Placebo-Controlled Trials of Desvenlafaxine for Major Depressive Disorder

    Science.gov (United States)

    Fayyad, Rana S.; Guico-Pabia, Christine J.

    2015-01-01

    Objective: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of desvenlafaxine for major depressive disorder (MDD). Method: Study 1: week 8 responders to open-label desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. Results: Overall relapse rates for all definitions were significantly lower for desvenlafaxine versus placebo for both studies (all P ≤ .002). In study 1, rates were significantly lower for desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. Trial Registration: ClinicalTrials.gov identifiers:NCT00887224 and NCT00075257 PMID:26137355

  15. Metronidazole (Flagyl) and Arnica Montana in the prevention of post-surgical complications, a comparative placebo controlled clinical trial.

    Science.gov (United States)

    Kaziro, G S

    1984-02-01

    A double blind trial, was designed, in which 118 patients undergoing the removal of impacted wisdom teeth were randomly divided into the following groups; 41 patients received Metronidazole, 39 patients received Arnica Montana, 38 patients received the placebo. Metronidazole was more effective in pain control than Arnica (p less than 0.001) and placebo (p less than 0.01). It prevented swelling better than Arnica (p less than 0.01) and placebo (p less than 0.05) and was more effective in promoting healing than Arnica (p less than 0.01) and placebo (p greater than 0.02). Arnica Montana appeared to give rise to greater pain than placebo (p less than 0.05) and caused more swelling than the placebo (p less than 0.01).

  16. The ethical use of placebo controls in clinical research: the Declaration of Helsinki.

    Science.gov (United States)

    La Vaque, T J; Rossiter, T

    2001-03-01

    Medical ethicists have questioned the use of no-treatment (placebo and sham procedure) controlled studies of new therapies when safe and effective standard therapies are available for use as an active or "equivalence" control. Current ethical principles of conduct for biomedical research specifically prohibit designs that withhold or deny "the best proven diagnostic and therapeutic" treatment to any participant in a clinical study, including those individuals who consent to randomization into a control group. Studies of psychophysiological therapies are often criticized on the grounds they lack a placebo or sham treatment control group. This paper briefly reviews the history of the problem and discusses the ethical standards that govern human research as derived from the Nuremberg Code and the Declaration of Helsinki. An examination of the problem with regard to research involving EEG biofeedback therapy for Attention-Deficit/Hyperactivity Disorder, Traumatic Brain Injury, and depression serves to highlight the issues. It is concluded that the active treatment control (treatment equivalence) design is most appropriate for those clinical studies examining disorders for which there is a known, effective treatment. Sham- or placebo-controlled studies are ethically acceptable for those disorders for which no effective treatment is available.

  17. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

    Science.gov (United States)

    Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

    2015-01-01

    Objectives To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Methods Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Results Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. Conclusions MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. Trial registration number NCT01023256 PMID:24534756

  18. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist's perspective

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    Lundeberg Thomas

    2009-01-01

    Full Text Available Abstract Placebo-control of acupuncture is used to evaluate and distinguish between the specific effects and the non-specific ones. During 'true' acupuncture treatment in general, the needles are inserted into acupoints and stimulated until deqi is evoked. In contrast, during placebo acupuncture, the needles are inserted into non-acupoints and/or superficially (so-called minimal acupuncture. A sham acupuncture needle with a blunt tip may be used in placebo acupuncture. Both minimal acupuncture and the placebo acupuncture with the sham acupuncture needle touching the skin would evoke activity in cutaneous afferent nerves. This afferent nerve activity has pronounced effects on the functional connectivity in the brain resulting in a 'limbic touch response'. Clinical studies showed that both acupuncture and minimal acupuncture procedures induced significant alleviation of migraine and that both procedures were equally effective. In other conditions such as low back pain and knee osteoarthritis, acupuncture was found to be more potent than minimal acupuncture and conventional non-acupuncture treatment. It is probable that the responses to 'true' acupuncture and minimal acupuncture are dependent on the aetiology of the pain. Furthermore, patients and healthy individuals may have different responses. In this paper, we argue that minimal acupuncture is not valid as an inert placebo-control despite its conceptual brilliance.

  19. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist's perspective.

    Science.gov (United States)

    Lund, Iréne; Näslund, Jan; Lundeberg, Thomas

    2009-01-30

    Placebo-control of acupuncture is used to evaluate and distinguish between the specific effects and the non-specific ones. During 'true' acupuncture treatment in general, the needles are inserted into acupoints and stimulated until deqi is evoked. In contrast, during placebo acupuncture, the needles are inserted into non-acupoints and/or superficially (so-called minimal acupuncture). A sham acupuncture needle with a blunt tip may be used in placebo acupuncture. Both minimal acupuncture and the placebo acupuncture with the sham acupuncture needle touching the skin would evoke activity in cutaneous afferent nerves. This afferent nerve activity has pronounced effects on the functional connectivity in the brain resulting in a 'limbic touch response'. Clinical studies showed that both acupuncture and minimal acupuncture procedures induced significant alleviation of migraine and that both procedures were equally effective. In other conditions such as low back pain and knee osteoarthritis, acupuncture was found to be more potent than minimal acupuncture and conventional non-acupuncture treatment. It is probable that the responses to 'true' acupuncture and minimal acupuncture are dependent on the aetiology of the pain. Furthermore, patients and healthy individuals may have different responses. In this paper, we argue that minimal acupuncture is not valid as an inert placebo-control despite its conceptual brilliance.

  20. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials.

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    Xianbin Li

    Full Text Available OBJECTIVE: To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. METHODS: POPULATION: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. INTERVENTIONS: adjunctive aripiprazole vs. adjunctive placebo. OUTCOME MEASURES: adverse events and efficacy of treatment. STUDIES: randomized controlled trials. RESULTS: Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158 prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed -0.05 to 0.04 (95% confidence interval -0.13 to 0.16; I(2 =0% to 68%, P=0.20 to 0.70. However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random 0.76 (95% confidence interval 0.67 to 0.85; I(2 =43%, P<0.00001. The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. CONCLUSION: Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.

  1. Efficacy of metronidazole versus placebo in pain control after hemorrhoidectomy: results of a controlled clinical trial

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    Sergio Solorio-López

    2015-11-01

    Full Text Available Introduction: Hemorrhoidal disease occurs in 50% of people aged > 40 years and is the most common reason for anorectal surgery. Pain is the main complication. Multiple topical and systemic drugs have been investigated for pain control, but there is no ideal treatment. Metronidazole has been shown to decrease postoperative pain but is not used widely. Objective: To evaluate the effect of oral metronidazole versus placebo and to assess postoperative pain following hemorrhoidectomy. Material and methods: Controlled clinical trial in adult patients who underwent elective hemorrhoidectomy for grade III/IV hemorrhoids. Patients were assigned to receive metronidazole (500 mg q8 h orally; study group, SG or placebo (control group, CG for 7 days after surgery. Pain was assessed using a visual analog scale after surgery. Analgesic administration (time and use of analgesics and resumption of daily life activities were also assessed. Results: Forty-four patients were included, 22 in each group. Postoperative pain differed significantly between the SG and CG at 6 h (3.86 ± 0.56, 6.64 ± 1.49, 12 h (5.59 ± 1.33, 8.82 ± 0.79, 24 h (6.86 ± 1.49, 9.73 ± 0.45, day 4 (5.32 ± 2.10, 9.50 ± 0.59, day 7 (3.14 ± 1.03, 7.36 ± 1.39, and day 14 (2.14 ± 0.46, 5.45 ± 1.29. The first analgesia dose was required at 21.27 ± 5.47 h in the CG and 7.09 ± 2.36 h in the SG (p < 0.05, the time of analgesic use was 6.86 ± 1.61 days in the CG and 13.09 ± 2.48 days in the SG (p < 0.05, and resumption of daily activities occurred at 7.59 ± 1.56 days in the CG and 14.73 ± 3.76 days in the SG (p < 0.05. Conclusion: Oral administration of metronidazole is effective in pain management after hemorrhoidectomy.

  2. [Placebo and placebo effect].

    Science.gov (United States)

    Aulas, J-J

    2005-11-01

    The word placebo appeared for the first time in an English medical dictionary in 1785. In French, it appeared much latter in 1958. This word defines an experimental tool used for rigourous evaluation of a specific effect of pharmacological treatment and the non specific effect of any therapy. The placebo effect is the strictly psychological or psychophysiological effect of a placebo. The two principal components of placebo effect as a pain killer, which has been extensively studied in this field, are positive expectancies of both the patient and the physician. Although the mechanisms of action of placebo effect are not well understood, results of several recent works are particularly interesting.

  3. Early mortality of alcoholic hepatitis: a review of data from placebo-controlled clinical trials.

    Science.gov (United States)

    Yu, Chao-Hui; Xu, Cheng-Fu; Ye, Hua; Li, Lan; Li, You-Ming

    2010-05-21

    To investigate the early mortality of placebo-treated alcoholic hepatitis patients. Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higher than that of general patients (22.69% vs 10.93%, P 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death.

  4. 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.

  5. Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Smith, Steven R; Stenlof, Kaj S; Greenway, Frank L; McHutchison, John; Schwartz, Susan M; Dev, Vidhu B; Berk, Evan S; Kapikian, Roxanne

    2011-09-01

    It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.

  6. Sensory testing of recipes masking peanut or hazelnut for double-blind placebo-controlled food challenges

    NARCIS (Netherlands)

    Ronteltap, A.; Schaik, van J.; Wensing, M.; Rynja, F.J.; Knulst, A.C.; Vries, de J.H.M.

    2004-01-01

    Background: In a double-blind placebo-controlled food challenge (DBPCFC), it is necessary that recipes comprising the allergen cannot be distinguished from placebo. Aims of the study: We investigated whether the method of paired comparisons, a sensory difference test, could be used to test the suita

  7. Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Pandina, Gahan J.; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

    2007-01-01

    Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n =…

  8. Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial.

    NARCIS (Netherlands)

    Jacobsen, D.E.; Samson, M.M.; Emmelot-Vonk, M.H.; Verhaar, H.J.

    2010-01-01

    OBJECTIVE: To compare the effects of raloxifene and placebo on body composition and muscle strength. DESIGN: Randomized, double-blind, placebo-controlled trial involving 198 healthy women aged 70 years or older conducted between July 2003 and January 2008 at the University Medical Centre, Utrecht, T

  9. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults

    Science.gov (United States)

    Omosa-Manyonyi, Gloria; Mpendo, Juliet; Ruzagira, Eugene; Kilembe, William; Chomba, Elwyn; Roman, François; Bourguignon, Patricia; Koutsoukos, Marguerite; Collard, Alix; Voss, Gerald; Laufer, Dagna; Stevens, Gwynn; Hayes, Peter; Clark, Lorna; Cormier, Emmanuel; Dally, Len; Barin, Burc; Ackland, Jim; Syvertsen, Kristen; Zachariah, Devika; Anas, Kamaal; Sayeed, Eddy; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Fast, Patricia; Priddy, Frances

    2015-01-01

    Background Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. Methods In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. Results The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. Conclusion Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses. Trial Registration ClinicalTrials.gov NCT01264445 PMID:25961283

  10. Stratification, Blinding and Placebo Effect in a Randomized, Double Blind Placebo-controlled Clinical Trial of Gold Bead Implantation in Dogs with Hip Dysplasia

    Directory of Open Access Journals (Sweden)

    Moe L

    2005-06-01

    Full Text Available The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore detected. Conclusion and Clinical Relevance: The age of the dogs influenced the outcome of the CHD treatment, and is recommended as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary in similar clinical studies.

  11. The challenge of recruiting patients into a placebo-controlled surgical trial

    DEFF Research Database (Denmark)

    Hare, Kristoffer B; Lohmander, L Stefan; Roos, Ewa M.

    2014-01-01

    patient into the RCT, 11.9 individuals needed to be screened. A total of 69% of participating patients considered the oral information to be the most important and the most common reason for participating was the contribution to research (90%). CONCLUSIONS: Patients are willing to participate...... in an orthopedic placebo-controlled surgical trial. Oral information given by the surgeon to the patient and the contribution to research are important aspects to enhance patient recruitment. TRIAL REGISTRATION: ClinicalTrials.gov NCT01264991, registered 21 December 2010....... component only adds to this complexity. The purpose of this study was to report the challenges of recruiting patients into an orthopedic placebo-controlled surgical trial, to determine the number of patients needed to be screened and allocated in order to include one participant into the trial...

  12. Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry.

    Science.gov (United States)

    Desselas, Emilie; Pansieri, Claudia; Leroux, Stephanie; Bonati, Maurizio; Jacqz-Aigrain, Evelyne

    2017-01-01

    Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients.

  13. Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry

    Science.gov (United States)

    Desselas, Emilie; Pansieri, Claudia; Leroux, Stephanie; Bonati, Maurizio; Jacqz-Aigrain, Evelyne

    2017-01-01

    Background Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. Methods We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Results Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Conclusion Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients. PMID:28192509

  14. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial.

    Science.gov (United States)

    Rahmani, Sepideh; Asgary, Sedigheh; Askari, Gholamreza; Keshvari, Mahtab; Hatamipour, Mahdi; Feizi, Awat; Sahebkar, Amirhossein

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Efficacy of Quetiapine Monotherapy in Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Villarreal, Gerardo; Hamner, Mark B; Cañive, José M; Robert, Sophie; Calais, Lawrence A; Durklaski, Valerie; Zhai, Yusheng; Qualls, Clifford

    2016-12-01

    This was a 12-week randomized, placebo-controlled trial to assess the efficacy of quetiapine monotherapy in the treatment of posttraumatic stress disorder (PTSD). Eighty patients were randomly assigned to treatment with either quetiapine or placebo. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS). Secondary efficacy measures included the CAPS subscales, the Davidson Trauma Scale, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scales for severity of Illness and improvement, the Hamilton Depression Rating Scale (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). Safety measurements included adverse events, vital signs, the Abnormal Involuntary Movement Scale, the Barnes Akathisia Scale, the Simpson-Angus Scale, and the Arizona Sexual Experiences Scale. After a 1-week placebo run-in, quetiapine was started at a daily dosage of 25 mg and increased to a maximum of 800 mg; the average was 258 mg (range, 50-800 mg). Reductions in CAPS total, re-experiencing, and hyperarousal scores were significantly greater for the quetiapine group than for the placebo group. Greater improvements were also observed for quetiapine in scores on the Davidson Trauma Scale, CGI severity and improvement ratings, PANSS positive symptom and general psychopathology subscales, HAM-A, and HAM-D than for placebo. Adverse events were generally mild and expected based on prior studies of quetiapine in this and other patient population. There were no differences in safety measures between groups. Quetiapine monotherapy was efficacious in the treatment of PTSD. These findings suggest quetiapine as a single agent is effective in treating military PTSD.

  16. A Randomized, Placebo Controlled Trial of Oral Zinc for Chemotherapy-Related Taste and Smell Disorders

    OpenAIRE

    Lyckholm, Laurel; Heddinger, Steven P.; Parker, Gwendolyn; Coyne, Patrick J.; Ramakrishnan, Viswanathan; Smith, Thomas J.; Henkin, Robert I.

    2012-01-01

    Abnormalities in taste and smell are commonly reported in patients receiving chemotherapy and may hinder appetite, dietary intake, nutritional well-being, and quality of life. Oral zinc has been used to treat taste and smell abnormalities in several altered physiologic states, including renal failure, liver disease, head trauma, and pregnancy, with varying results. The authors conducted a double-blinded, placebo-controlled randomized clinic trial over 3 months. Eligible patients were those ta...

  17. Randomized, Placebo-Controlled Clinical Trial of Omega-3 as Supplemental Treatment in Schizophrenia

    OpenAIRE

    Jamilian, Hamidreza; Solhi, Hasan; Jamilian, Mehri

    2014-01-01

    Introduction: Recent studies found omega-3 fatty acid deficiency in brain cell membranes of schizophrenic patients. Conventional antipsychotics have many adverse reactions. Safety, availability and low price made omega-3 as a potential supplement for treatment of these patients. This study investigated the efficacy of omega-3 fatty acid as add-on treatment in schizophrenia. Material & Methods: A randomized, double blind, placebo controlled fixed-dose, add-on clinical trial conducted over 8 we...

  18. Pragmatic consideration of recent randomized, placebo-controlled clinical trials for treatment of fibromyalgia.

    Science.gov (United States)

    Holman, Andrew J

    2008-12-01

    A flurry of recent randomized, placebo-controlled trials assessing dissimilar pharmacotherapeutic treatment options for fibromyalgia (FM) have been presented in the past few years. This review evaluates these trials in light of recent pathophysiological concepts germane to FM, including mood disorders, autonomic dysregulation, altered sleep stage architecture, and the diagnostic tender point controversy. Studies with gabapentin, pregabalin, duloxetine, milnacipran, sodium oxybate, and pramipexole for treatment of FM are discussed.

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

    Science.gov (United States)

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

    2017-01-01

    Abstract 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

  20. International collaborative trials, placebo controls and The Declaration of Helsinki: need for clarification in paragraph 32.

    Science.gov (United States)

    Malik, A Y; Ghafoor, F

    2012-01-01

    Inequities in socio-economic and healthcare systems between developed and developing countries have been thrown into sharp relief by globalisation. At the same time, pharmaceutical companies have started conducting clinical trials in developing countries in order to reduce their costs substantially. Together, these two developments create ethical challenges for sponsors and researchers of these trials. One such challenge is that of placebo-controlled trials (PCTs). In this paper we analyse Paragraph 32 of the Declaration of Helsinki referring to PCTs, identifying ambiguities in the wording, and then examine three arguments presented by sponsors of PCTs in developing countries, in defence of such trials. These arguments are: (i) a placebo control provides a definitive answer, and is therefore methodologically superior; (ii) placebo-controlled trials are ethical because they serve the principle of utility, and (iii) interpreting the "best current proven intervention" as the local standard of care allows PCTs to be conducted, if the local standard of care is "no treatment". We argue that PCTs are not methodologically superior; nor are they ethically defensible. Other trial designs conforming to the ethics of research are feasible; the reason for conducting PCTs is expediency. We further propose that, given the global applicability of the Declaration of Helsinki, it is imperative to remove the ambiguities in Paragraph 32. In the context of collaborative trials, when a treatment exists, conducting PCTs is ethically unacceptable, irrespective of the geographic location of the trial. Universal standards ought to be applied universally.

  1. 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

  2. Superior efficacy of St John's wort extract WS® 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298

    Directory of Open Access Journals (Sweden)

    Dienel Angelika

    2006-06-01

    Full Text Available Abstract Background The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort extract WS® 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses. Methods The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria. As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS® 5570 600 mg/day, 127 to WS® 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination. Results After 6 weeks of treatment, mean ± standard deviation decreases in HAM-D total scores of 11.6 ± 6.4, 10.8 ± 7.3, and 6.0 ± 8.1 points were observed for the WS® 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis. Secondary measures of treatment efficacy also showed that both WS® 5570 groups were statistically superior to placebo. Significantly more patients in the WS® 5570 treatment groups than in the placebo group showed treatment response and remission. WS® 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS® 5570 1200 mg/day group than the WS® 5570 600 mg/day group. The incidence of adverse events was low in

  3. Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study.

    Science.gov (United States)

    Chen, Chun-Chung; Wei, Sung-Tai; Tsaia, Shiu-Chiu; Chen, Xian-Xiu; Cho, Der-Yang

    2013-12-01

    In adults, mild traumatic brain injury (MTBI) frequently results in impairments of cognitive functions which would lead to psychological consequences in the future. Cerebrolysin is a nootropic drug, and can significantly improve cognitive function in patients with Alzheimer's disease and stroke. The purpose of this study was to investigate how Cerebrolysin therapy enhances cognitive recovery for mild traumatic brain injury patients using a double-blinded, placebo-controlled, randomized phase II pilot study. Patients having head injury within 24 h sent to our hospital were screened and recruited if patients were alert and conscious, and had intracranial contusion haemorrhage. From July 2009 to June 2010, totally, thirty-two patients were recruited in the double-blinded, placebo-controlled, and randomized study. Patients were randomized to receive Cerebrolysin (Group A, once daily intravenous infusion of 30 mL Cerebrolysin over a 60-min period for 5 days) or placebo (Group B, same dosage and administration of normal saline as Group A). The primary outcome measures were differences of cognitive function including Mini-Mental Status Examination (MMSE), and Cognitive Abilities Screening Instrument (CASI) scores between baseline and week 1, between baseline and week 4, and between baseline and week 12. Thirty-two patients completed the trial. For Group A, the CASI score difference between baseline and week 12 was 21.0 ± 20.4, a significantly greater change than that of Group B (7.6 ± 12.1) (p = 0.0461). Besides, drawing function (one of the domains of CASI; p = 0.0066) on week 4 and both drawing function (p = 0.0472) and long-term memory (one of the domains of CASI; p = 0.0256) on week 12 were also found to be significantly improved in the patients receiving Cerebrolysin treatment. Our results suggest that Cerebrolysin improves the cognitive function of the MTBI in patients at 3rd month after injury, especially for long-term memory and drawing function.

  4. Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram.

    Science.gov (United States)

    Bachman, E A; Senapati, S; Sammel, M D; Kalra, S K

    2014-06-01

    Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group

  5. Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

    Science.gov (United States)

    Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

    2016-03-01

    To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

  6. 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.

  7. 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

    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 signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple...... 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......-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated....

  8. Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial.

    Science.gov (United States)

    Braam, Wiebe; Didden, Robert; Smits, Marcel G; Curfs, Leopold M G

    2008-06-01

    Previous studies suggested that melatonin improves sleep in insomniac patients with Angelman syndrome. To assess the efficacy of melatonin, a randomized placebo-controlled study was conducted in 8 children with Angelman syndrome with idiopathic chronic insomnia. After a 1-week baseline period, patients received, depending on age, either melatonin 5 or 2.5 mg, or placebo, followed by 4 weeks of open treatment. Parents recorded lights off time, sleep onset time, wake-up time, and epileptic seizures in a diary. Salivary melatonin levels were measured at baseline and the last evening of the fourth treatment week. Melatonin significantly advanced sleep onset by 28 minutes, decreased sleep latency by 32 minutes, increased total sleep time by 56 minutes, reduced the number of nights with wakes from 3.1 to 1.6 nights a week, and increased endogenous salivary melatonin levels. Parents were satisfied with these results. Indications that melatonin dose in Angelman syndrome patients should be low, are discussed.

  9. Treatment of chronic depression with sulpiride: evidence of efficacy in placebo-controlled single case studies.

    Science.gov (United States)

    Maier, W; Benkert, O

    1994-08-01

    Systematic variation of treatment (alternating active drug and placebo in four treatment periods) in individual patients is proposed to collect preliminary evidence for a therapeutic effect of sulpiride in chronic depression; the ARIMA model is applied to evaluate the intervention effects of the tentatively effective treatment in single subjects. Ten single cases of chronic depression with a diagnosis of major depression or dysthymia were selected and seven of these provided evidence for beneficial effects of sulpiride with regard to treating the symptoms of depression and anxiety. However, the drug effects were intraindividually not always replicable. The results obtained with these single cases positively support the recommendation to perform regular randomized placebo-controlled trials with sulpiride in chronic depression. Simultaneously, these single case investigations reveal a lack of temporal stability of treatment response and inconsistencies of response with regard to different treatment targets in individual patients.

  10. A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Shiraishi Tetsuya

    2010-06-01

    Full Text Available Abstract Background Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia. Methods A randomised, placebo-controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day or placebo (n = 20 in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS, Cambridge Neuropsychological Test Automated Battery (CANTAB, and Positive and Negative Syndrome Scale (PANSS scores were measured. Results In all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non-smoking patients, were significantly improved by tropisetron trial. Conclusions This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.

  11. Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial.

    Science.gov (United States)

    Clayton, Anita H; Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

    2015-07-01

    Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc analyses evaluated change from baseline to week 10 on the Changes in Sexual Functioning Questionnaire (CSFQ); no inferential statistics were performed. CSFQ scores increased for women [1.2 (citalopram) to 3.0 (vilazodone 40 mg)] and men [1.2 (vilazodone 40 mg) to 3.5 (placebo)] in all treatment groups. Greater changes in CSFQ scores were seen in responders [women: 2.33 (citalopram) to 5.06 (vilazodone 40 mg); men: 2.26 (vilazodone 40 mg) to 4.35 (placebo)] versus nonresponders. CSFQ change from baseline was small for patients with normal baseline sexual function; in patients with baseline sexual dysfunction, CSFQ scores improved across groups [women: 2.35 (citalopram) to 4.52 (vilazodone 40 mg); men 2.83 (vilazodone 40 mg) to 6.43 (placebo)]. Across treatment groups, baseline sexual function improved in women and men, MDD responders, and patients with baseline sexual dysfunction.

  12. 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

  13. General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2016-01-01

    of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying...... was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine......BACKGROUND: The Clinical Trials Subcommittee of the International Headache Society (IHS) recommends that a placebo arm is included in comparative randomised clinical trials (RCTs) of multiple prophylactic drugs due to the highly variable placebo response in migraine prophylaxis studies. The use...

  14. Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial

    OpenAIRE

    Clayton, Anita H.; Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

    2015-01-01

    Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc...

  15. 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...

  16. Selective decontamination of the digestive tract to prevent postoperative infection : A randomized placebo-controlled trial in liver transplant patients

    NARCIS (Netherlands)

    Zwaveling, JH; Maring, JK; Klompmaker, IJ; Haagsma, EB; Bottema, JT; Winter, Heinrich L.J.; van Enckevort, PJ; TenVergert, EM; Metselaar, HJ; Bruining, HA; Slooff, MJH

    Objective., To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver. Design: Randomized, double-blind, placebo-controlled study. Setting. Two academic teaching hospitals. Patients. Adult patients undergoing

  17. Does yohimbine hydrochloride facilitate fear extinction in virtual reality treatment of fear of flying? A randomized placebo-controlled trial

    NARCIS (Netherlands)

    Meyerbroeker, K.; Powers, M.B.; van Stegeren, A.; Emmelkamp, P.M.G.

    2012-01-01

    BACKGROUND: Research suggests that yohimbine hydrochloride (YOH), a noradrenaline agonist, can facilitate fear extinction. It is thought that the mechanism of enhanced emotional memory is stimulated through elevated noradrenaline levels. This randomized placebo-controlled trial examined the

  18. Protection of salivary function by concomitant pilocarpine during radiotherapy : A double-blind, randomized, placebo-controlled study

    NARCIS (Netherlands)

    Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.; Coppes, Rob P.; Terhaard, Chris; Langendijk, Johannes A.; van Luijk, Peter; Stokman, Monique A.; Vissink, Arjan

    2008-01-01

    Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with

  19. Selective decontamination of the digestive tract to prevent postoperative infection : A randomized placebo-controlled trial in liver transplant patients

    NARCIS (Netherlands)

    Zwaveling, JH; Maring, JK; Klompmaker, IJ; Haagsma, EB; Bottema, JT; Winter, Heinrich L.J.; van Enckevort, PJ; TenVergert, EM; Metselaar, HJ; Bruining, HA; Slooff, MJH

    2002-01-01

    Objective., To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver. Design: Randomized, double-blind, placebo-controlled study. Setting. Two academic teaching hospitals. Patients. Adult patients undergoing elec

  20. 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. PARTICIPANTS:

  1. 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

  2. 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

  3. 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. PARTICIPANTS:

  4. Citalopram, Methylphenidate, or Their Combination in Geriatric Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

    National Research Council Canada - National Science Library

    Lavretsky, Helen; Reinlieb, Michelle; St. Cyr, Natalie; Siddarth, Prabha; Ercoli, Linda M; Senturk, Damla

    2015-01-01

    ... patients.Method:The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups...

  5. 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...

  6. 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,

  7. 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...

  8. [Probiotic prophylaxis in patients with predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial

    NARCIS (Netherlands)

    Besselink, M.G.; Santvoort, H.C. van; Buskens, E.; Boermeester, M.A.; Goor, H. van; Timmerman, H.M.; Nieuwenhuijs, V.B.; Bollen, T.L.; Ramshorst, B. van; Witteman, B.J.M.; Rosman, C.; Ploeg, R.J.; Brink, M.; Schaapherder, A.F.; Dejong, C.H.; Wahab, P.J.; Laarhoven, C.J.H.M. van; Harst, E. van der; Eijck, C.H. van; Cuesta, M.A.; Akkermans, L.M.; Gooszen, H.G.

    2008-01-01

    OBJECTIVE: To evaluate whether enteral prophylaxis with probiotics in patients with predicted severe acute pancreatitis prevents infectious complications. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. METHOD: A total of 296 patients with predicted severe acute pancreatitis

  9. Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

    2014-06-01

    We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. © 2013 The British Pharmacological Society.

  10. MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial.

    Science.gov (United States)

    Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

    2015-06-01

    To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. NCT01023256. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. 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.

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

    Science.gov (United States)

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

    2013-03-01

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

  13. Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison.

    Science.gov (United States)

    Kornmann, O; Dahl, R; Centanni, S; Dogra, A; Owen, R; Lassen, C; Kramer, B

    2011-02-01

    Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (pindacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.

  14. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Park, Soo-Hyun; Huh, Tae-Lin; Kim, Sun-Young; Oh, Mi-Ra; Tirupathi Pichiah, P B; Chae, Soo-Wan; Cha, Youn-Soo

    2014-01-01

    The effects of actiponin was investigated, a heat-processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers of Korean participants in a 12-week, randomized, double-blind, placebo-controlled clinical trial. Obese participants (BMI ≥ 25 kg m(-2) and WHR ≥ 0.90 for male or WHR ≥ 0.85 for female) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day(-1) ) and placebo (n = 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs). During 12-week of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group compared to the placebo group. No clinically significant changes in any safety parameter were observed. Our study revealed that actiponin is a potent antiobesity reagent that does not produce any significant adverse effects. These results suggest that actiponin supplementation may be effective for treating obese individuals. Copyright © 2013 The Obesity Society.

  15. Cantharidin for the Treatment of Molluscum Contagiosum: A Prospective, Double-Blinded, Placebo-Controlled Trial

    Science.gov (United States)

    Dosal, Jacquelyn Coloe; Stewart, Paul W.; Lin, Ja-An; Williams, Christianna S.; Morrell, Dean S

    2012-01-01

    Background/Objective To study the effects and safety of cantharidin in the treatment of molluscum contagiosum. Methods We conducted a prospective, double-blinded, placebo-controlled, randomized clinical trial to evaluate the safety and efficacy of topical cantharidin for treatment of pediatric molluscum contagiosum in an academic ambulatory care center. Twenty-nine children aged 5–10 with the diagnosis of molluscum contagiosum were enrolled to receive treatment with cantharidin or placebo. The main outcome measure was complete clearance of molluscum lesions. Results In contrast to previous retrospective observational studies, the performance of cantharidin treatment over 2 months was not substantially better than the performance of placebo. Limitations The scope of follow-up was limited to 5 visits over 2 months of treatment. In hindsight, we can hypothesize that a longer follow up period may have captured a greater effect of cantharidin. Conclusion We conclude that during a 2 month period, the magnitude of the cantharidin treatment effects in the target population are, at best, not large. This study provided objective unbiased estimates of the magnitude of cantharidin treatment effects and provided important prospective safety data. Our subjects experienced minimal side effects when treated with cantharidin. PMID:22897595

  16. 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.

  17. A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function.

    Science.gov (United States)

    Wilkie, M E; Beer, J C; Evans, S J; Raftery, M J; Lord, R H; Moore, R; Marsh, F P

    1994-01-01

    A double-blind, randomized, placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin (CsA), prednisolone and azathioprine. Fifty adult cadaveric renal allograft recipients were randomized to placebo (group P n = 17), nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 48 h, followed by matching placebo for 3 months (group NS n = 16) or nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 3 months (group NL n = 17). Donor and recipient exclusion criteria included recent calcium antagonist treatment. At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS (mean +/- SD 61 +/- 28 versus 34 +/- 25 ml/min/1.73 m2; P nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin.

  18. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study

    OpenAIRE

    Teughels, Wim; Durukan, Andaç; Ozcelik, Onur; Pauwels, Martine; Quirynen, Marc; Haytac, Mehmet Cenk

    2013-01-01

    Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M, Haytac MC. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol 2013; 40: 1025–1035. doi: 10.1111/jcpe.12155. AimThe aim of this randomized placebo-controlled clinical trial was to evaluate the effects of Lactobacillus reuteri-containing probiotic lozenges as an adjunct to scaling and root planing (SRP). Material and ...

  19. Dialysis-Associated Hypertension Treated with Telmisartan - DiaTel: A Pilot, Placebo-Controlled, Cross-Over, Randomized Trial: e79322

    National Research Council Canada - National Science Library

    Matthias Huber; Till Treutler; Peter Martus; Antje Kurzidim; Reinhold Kreutz; Joachim Beige

    2013-01-01

    .... 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...

  20. A randomized, double-blinded, placebo-controlled trial of intercostal nerve block after percutaneous nephrolithotomy.

    Science.gov (United States)

    Honey, R John D'A; Ghiculete, Daniela; Ray, A Andrew; Pace, Kenneth T

    2013-04-01

    The optimal method of pain control after percutaneous nephrolithotomy (PCNL) remains controversial. We sought to determine whether intercostal nerve block with bupivicaine provided superior pain control, when compared with placebo, with a lower need for narcotics and improved health-related quality of life (HRQL) in the immediate postoperative period. Sixty-three patients were randomized to receive intercostal blockade with either 20 mL of 0.5% bupivacaine with epinephrine or 20 mL physiologic saline. All patients received intravenous narcotic patient-controlled analgesia (PCA) postoperatively. Data were collected on stone parameters, demographics, analgesic usage, length of stay, and HRQL as assessed by the Postoperative Recovery Scale. The mean age was 47.7±1.2 years; mean body mass index was 28.0±5.0 kg/m(2); mean stone diameter was 29.2±15.8 mm. Within the first 3 to 6 hours after surgery, there was a significant reduction in narcotic use for the group receiving intercostal nerve blockade with bupivacaine compared with placebo. At 3 hours, narcotic use was 2.4±3.1 mg vs 4.3±3.8 mg morphine equivalents (P=0.034), and within 6 hours of surgery, narcotic use was 5.9±6.1 mg vs 8.8±7.4 mg (P=0.096). Durable improvement in HRQL was also observed in patients receiving intercostal nerve blockade with bupivacaine compared with placebo (P=0.034). No complications were attributable to the intercostal nerve blocks in either group. Intercostal blockade with bupivacaine significantly improves both pain control and HRQL in the early postoperative period. The effectiveness of bupivacaine disappears within 6 hours of surgery, after which narcotic use becomes indistinguishable. Intercostal nerve blockade is an easy, safe, and inexpensive method that can be used to optimize pain control after PCNL.

  1. A RANDOMIZED CONTROLLED PLACEBO STUDY OF DEXTROSE IONTOPHORESIS VERSUS DEXTROSE PROLOTHERAPY IN CASE OF KNEE OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    Mahmoud Mohamed Ahmed Ewidea

    2015-12-01

    Full Text Available Background: Osteoarthritis is the most common cause of musculoskeletal pain and disability in the knee joint. This study investigated the efficacy of Dextrose iontophoresis versus Dextrose prolotherapy in case of knee osteoarthritis in a randomized, placebo-controlled, double-blinded study. Methods: sixty patients diagnosed mild to moderate osteoarthritis were included in the study. Their age's were45:65 years with mean age 51 ± 3.5 years. Patients were divided randomly into three equal groups, group (Areceived 50 % dextrose iontophoresis, group (B Each patient received three intra-articular injections of dextrose at 1-month intervals in weeks 0, 4, and 8 and group (C received sham iontophoresis. The outcome measurements were Western Ontario and McMaster Universities arthritis index (WOMAC values, knee ROM, and pain severity at rest (seated and in activity (after walking 6 m using the visual analogue scale (VAS were recorded. The patients were evaluated for these parameters before allocated in their groups then after 4, 8, and 24 weeks later. Results: compared to sham group (placebo there were significant improvement of VAS and ROM of iontophoresis group than sham (placebo group (p<0.000. Also there were significant improvement of prolotherapy group than placebo (p<0.006, and 0.02 respectively. Furthermore there was significant improve of iontophoresis group than prolotherapy where p was <0.000 for VAS, ROM and (WOMAC. Conclusion: The results of this study suggested that both dextrose iontophoresis and dextrose prolotherapy may be as useful modalities in treatment of osteoarthritis with better effects of dextrose iontophoresis than prolotherapy.

  2. Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study.

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    Shawn D Aaron

    Full Text Available BACKGROUND: Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF. METHODS: We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18 or placebo (N = 17 for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1 and quality of life. RESULTS: Over the 24 week treatment period, 4 of 18 (22% patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31% placebo treated patients, P = 0.70. FEV(1 declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34. Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole. CONCLUSION: We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00528190.

  3. A randomized placebo-controlled trial of ataluren for the treatment of nonsense mutation cystic fibrosis

    Science.gov (United States)

    EitanKerem; Konstan, Michael W.; De Boeck, Kris; Accurso, Frank J.; Sermet-Gaudelus, Isabelle; Wilschanski, Michael; Elborn, J S; Melotti, Paola; Bronsveld, Inez; Fajac, Isabelle; Malfroot, Anne; Rosenbluth, Daniel B.; Walker, Patricia A.; McColley, Susanna A.; Knoop, Christiane; Quattrucci, Serena; Rietschel, Ernst; Zeitlin, Pamela L.; Barth, Jay; Elfring, Gary L.; Welch, Ellen M.; Branstrom, Arthur; Spiegel, Robert J.; Peltz, Stuart W.; Ajayi, Temitayo; Rowe, Steven M.

    2014-01-01

    Background Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis (CF) in 10% of patients.. Methods This randomized, double-blind, placebo-controlled study enrolled 238 patients ≥6 years with nmCF to receive oral ataluren 10 mg/kg in the morning, 10 mg/kg mid-day, and 20 mg/kg in the evening or matching placebo for 48 weeks. The primary endpoint was relative change in % predicted forced expiratory volume in one second (FEV1) at Week 48; the secondary endpoint was the rate of pulmonary exacerbations. This study is registered with ClinicalTrials.gov, number NCT00803205. Findings There was no statistically significant difference in relative change from baseline in % predicted FEV1between ataluren and placebo at Week 48(-2•5% vs -5•5%, p=0.1235). The rate of pulmonary exacerbations was not statistically different between treatment arms (rate ratio 0.77 (95% CI 0.57, 1.05), p=0.0992). However, post hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5.7% difference in relative change from baseline in % predicted FEV1 between ataluren and placebo at Week 48 (-0.7% vs -6.4%, nominal p=0•008, adjusted for multiplicity p = 0•024) and 40% fewer exacerbations in ataluren-treated patients (OR 0.60 (95% CI 0•42, 0•86), nominal p=0•006, adjusted for multiplicity p = 0•018). Interpretation While there was no statistically significant improvement in lung function or exacerbation rate in the ITT population of cystic fibrosis patients with nonsense mutations treated with ataluren, treatment might be beneficial for nmCF patients not receiving chronic inhaled tobramycin. PMID:24836205

  4. 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.

  5. Open-label placebo treatment in chronic low back pain: a randomized controlled trial

    Science.gov (United States)

    Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J.; Kirsch, Irving

    2016-01-01

    Abstract This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland–Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (−0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain. PMID:27755279

  6. 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.

  7. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies.

    Science.gov (United States)

    Jacqz-Aigrain, E; Daoud, P; Burtin, P; Desplanques, L; Beaufils, F

    1994-09-03

    Although midazolam is used for sedation of mechanically ventilated newborn babies, this treatment has not been evaluated in a randomised trial. We have done a prospective placebo-controlled study of the effects of midazolam on haemodynamic variables and sedation as judged by a five-item behaviour score. 46 newborn babies on mechanical ventilation for respiratory distress syndrome were randomly assigned to receive midazolam (n = 24) or placebo (n = 22) as a continuous infusion. Doses of midazolam were calculated to obtain plasma concentrations between 200 and 1000 ng/mL within 24 h of starting treatment and to maintain these values throughout the study. Haemodynamic and ventilatory variables were noted every hour, as were complications and possible side-effects of treatment. Mean (SD) duration of inclusion was 78.7 (30.9) h. 1 patient in the treatment group and 7 in the placebo group were withdrawn because of inadequate sedation (p < 0.05). Midazolam gave a significantly better sedative effect than placebo, as estimated by the behaviour score (p < 0.05). Heart rate and blood pressure were reduced by treatment but remained within the normal range for gestational age and there was no effect on ventilatory indices. The incidence of complications was similar in the two groups. No midazolam-related side-effects were noted. Continuous infusion of midazolam at doses adapted to gestational age induces effective sedation in newborn babies on mechanical ventilation, with positive effects on haemodynamic variables. The course of the respiratory distress syndrome was not influenced by this treatment. Midazolam was given over only a few days and the limited effects on heart rate and blood pressure that we report should not encourage long-term administration.

  8. [Postoperative transcutaneous electrical nerve stimulation (TENS) in shoulder surgery (randomized, double blind, placebo controlled pilot trial)].

    Science.gov (United States)

    Likar, R; Molnar, M; Pipam, W; Koppert, W; Quantschnigg, B; Disselhoff, B; Sittl, R

    2001-06-01

    The aim of this study was to determine whether 3 days of TENS therapy postoperatively after shoulder operations would result in better pain relief and/or reduced analgesic intake when compared to placebo. The study was carried out randomized, double-blind and placebo controlled. Thirty patients were randomized to two groups. The verum group received TENS SM1AKS 80 Hz 6 mA and the placebo group received TENS SM1AKS 80 Hz 0 mA. The pain was assessed pre-operatively using the Hamburg Pain Adjective List. Premedication and Anaesthesia were standardized. TENS was applied to the patients immediately postoperatively for 8 hours and then on the following days 5 times daily for 45 minutes. The effectiveness was evaluated postoperatively using a visual analogue scale (rest, activity), the Hamburg Pain Adjective List and postoperative analgesic consumption. The visual analogue scale at rest and on activity showed no significant difference between the groups. Postoperative analgesic consumption of morphine hydrochloride in the first 24 hours was at time 8 hours postoperative significantly and at all other time points markedly less in the verum group compared to the placebo group. The sensory secondary scale score of the "Hamburg Pain Adjective List" was significantly lower postoperatively compared to preoperatively in the verum group. We were able to show in this study that TENS applied postoperatively after shoulder surgery clearly reduced analgesic consumption in the first 72 hours. Furthermore there was a significant difference in the pain scores using the "Hamburg Pain Adjective List" in favour of the verum group. TENS applied postoperatively is a effective, simple modality with few side-effects.

  9. 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

  10. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Brusselle, Guy G; Vanderstichele, Christine; Jordens, Paul; Deman, René; Slabbynck, Hans; Ringoet, Veerle; Verleden, Geert; Demedts, Ingel K; Verhamme, Katia; Delporte, Anja; Demeyere, Bénédicte; Claeys, Geert; Boelens, Jerina; Padalko, Elizaveta; Verschakelen, Johny; Van Maele, Georges; Deschepper, Ellen; Joos, Guy F P

    2013-04-01

    Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. CLINICALTRIALS.GOV NUMBER

  11. Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stéphanie J.E. Becker

    2014-09-01

    Full Text Available Background:  The primary aim of this study was to determine predictors of missed research appointments in a prospective  andomized placebo injection-controlled trial with evaluations 1 to 3 and 5 to 8 months after enrollment.   Methods:  This study represents a secondary use of data from 104 patients that were enrolled in a prospective randomized  ontrolled trial of dexamethasone versus lidocaine (placebo injection for various diagnoses. Patients were enrolled between June 2003 and February 2008. Sixty-three patients (61% had lateral epicondylosis, 17 patients (16% had trapeziometacarpal arthrosis, and 24 patients (23% had de Quervain syndrome. Each patient completed a set of questionnaires at time of enrollment. Bivariable and multivariable analyses were used to determine factors associated with missed research appointments.  Results:  Fourteen patients (13% did not return for the first follow-up and 33 patients (32% did not return for the second follow-up. The best multivariable logistic regression model for missing the first research visit explained 35% of the variability and included younger age, belief that health can be controlled, and no college education. The best model for missing the second research visit explained 17% of the variability and included greater pain intensity, less personal responsibility for health, and diagnosis (trapeziometacarpal arthrosis and de Quervain syndrome. Conclusions:  Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial.

  12. PROMISe trial: a pilot, randomized, placebo-controlled trial of magnetic resonance guided focused ultrasound for uterine fibroids.

    Science.gov (United States)

    Jacoby, Vanessa L; Kohi, Maureen P; Poder, Liina; Jacoby, Alison; Lager, Jeanette; Schembri, Michael; Rieke, Viola; Grady, Deborah; Vittinghoff, Eric; Coakley, Fergus V

    2016-03-01

    To evaluate the feasibility of a full-scale placebo-controlled trial of magnetic resonance-guided focused ultrasound for fibroids (MRgFUS) and obtain estimates of safety and efficacy. Pilot, randomized, placebo-controlled trial. University medical center. Premenopausal women with symptomatic uterine fibroids. Participants randomized in a 2:1 ratio to receive MRgFUS or placebo procedure. change in fibroid symptoms from baseline to 4 and 12 weeks after treatment assessed by the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QOL); secondary outcome: incidence of surgery or procedures for recurrent symptoms at 12 and 24 months. Twenty women with a mean age of 44 years (±standard deviation 5.4 years) were enrolled, and 13 were randomly assigned to MRgFUS and 7 to placebo. Four weeks after treatment, all participants reported improvement in the UFS-QOL: a mean of 10 points in the MRgFUS group and 9 points in the placebo group (for difference in change between groups). By 12 weeks, the MRgFUS group had improved more than the placebo group (mean 31 points and 13 points, respectively). The mean fibroid volume decreased 18% in the MRgFUS group with no decrease in the placebo group at 12 weeks. Two years after MRgFUS, 4 of 12 women who had a follow-up evaluation (30%) had undergone another fibroid surgery or procedure. Women with fibroids were willing to enroll in a randomized, placebo-controlled trial of MRgFUS. A placebo effect may explain some of the improvement in fibroid-related symptoms observed in the first 12 weeks after MRgFUS. NCT01377519. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Adverse events during a placebo phase for inpatients with chronic schizophrenia

    NARCIS (Netherlands)

    van de Laar, N; Henter, L; Bartko, JJ; Wyatt, RJ

    2001-01-01

    Background: This report builds on a previous analysis examining the long-term effects of a placebo period on a group of inpatients with chronic schizophrenia. In the present analysis, outcome was evaluated through the use of the Psychiatric Adverse Events Rating Scale. Methods: This retrospective an

  14. 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...

  15. Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Miyaoka

    2015-01-01

    Full Text Available Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS. Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS and intention-to-treat (ITT. However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: −0.23±0.08; placebo: −0.03±0.08, P<0.018, tension (TJ-54: −0.42±0.09; placebo: −0.18±0.09, P<0.045, and poor impulse control (TJ-54: −0.39±0.10; placebo: −0.07±0.10, P<0.037. Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

  16. Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial.

    Science.gov (United States)

    Binder, Andreas; Bruxelle, Jean; Rogers, Peter; Hans, Guy; Bösl, Irmgard; Baron, Ralf

    2009-01-01

    Post-herpetic neuralgia (PHN) is a distressing neuropathic pain condition mainly affecting elderly patients. Neuropathic pain symptoms can be of a burning, shooting and stabbing nature, and may continue for prolonged periods and are often poorly controlled by polymedication. The aim of this study was to evaluate the analgesic efficacy and safety of topical analgesic treatment (5% lidocaine [lignocaine] medicated plaster) compared with placebo plaster in patients with PHN. This was a double-blind, placebo plaster-controlled, parallel-group, multicentre study employing enriched enrolment with randomized withdrawal methodology. After an initial 8-week open-label, active run-in phase, responders entered a 2-week randomized, double-blind, placebo-controlled phase. The study was conducted at 33 outpatient investigational centres in 12 European countries. Patients with PHN were selected who were aged >/=50 years, had experienced neuropathic pain persisting for >/=3 months after rash healing, and had a mean pain intensity of >/=4 on an 11-point numerical rating scale. A total of 265 patients entered the open-label phase and subsequently a pre-defined number of 71 patients entered the randomized phase. Patients applied up to three 5% lidocaine medicated plasters for up to 12 hours per day. The primary endpoint of the study was time-to-exit due to a >/=2-point reduction in pain relief on two consecutive days of plaster application using a 6-point verbal rating scale. Of the 265 patients entering the run-in phase, 51.7% achieved at least moderate pain relief. In the double-blind phase (full analysis set, n = 71), median times-to-exit were 13.5 (range 2-14) and 9.0 (range 1-14) days for lidocaine and placebo plaster groups, respectively (p = 0.151). For per-protocol patients (n = 34), median time-to-exit was 14.0 (range 3-14) and 6.0 (range 1-14) days for lidocaine and placebo plaster groups, respectively (p = 0.0398). Drug-related adverse events occurred in 13.6% of patients

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

    Science.gov (United States)

    Scholey, Andrew; Benson, Sarah; Gibbs, Amy; Perry, Naomi; Sarris, Jerome; Murray, Greg

    2017-01-01

    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. PMID:28218661

  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. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L)

    National Research Council Canada - National Science Library

    Riddle, Matthew C; Aronson, Ronnie; Home, Philip; Marre, Michel; Niemoeller, Elisabeth; Miossec, Patrick; Ping, Lin; Ye, Jenny; Rosenstock, Julio

    2013-01-01

    ...). We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20...

  20. 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.

  1. Reducing depressive symptomatology with a smartphone app: study protocol for a randomized, placebo-controlled trial.

    Science.gov (United States)

    Giosan, Cezar; Cobeanu, Oana; Mogoaşe, Cristina; Szentagotai, Aurora; Mureşan, Vlad; Boian, Rareș

    2017-05-12

    weeks. A short therapist check-in via phone will take place every week. Participants in the delayed-intervention condition will be given access to the app after 6 weeks from randomization. The primary outcome is the level of depressive symptomatology. The intervention delivered through the app to the active condition includes psychoeducational materials and exercises based on CBT for depression, while the placebo intervention uses a sham version of the app (i.e., similar structure of courses and exercises). To our knowledge, this study protocol is the first to test the efficacy of a smartphone app for depressive symptomatology in the form of a randomized controlled trial (RCT) that includes an active placebo condition. As such, this can substantially add to the body of evidence supporting the use of apps designed to decrease depression. ClinicalTrials.gov, identifier: NCT03060200 . Registered on 1 February 2017. The first participant was enrolled on 17 February 2017.

  2. Efficacy and safety of drotaverine hydrochloride in irritable bowel syndrome: A randomized double-blind placebo-controlled study

    OpenAIRE

    Ramesh R Rai; Manisha Dwivedi; Nirmal Kumar

    2014-01-01

    Backgrounds/Aims: To study the efficacy and safety of drotaverine hydrochloride (HCl) 80 mg tablet given thrice a day in the symptomatic relief of patients with irritable bowel syndrome (IBS). Patients and Methods: The study was a multicentric, randomized, double-blind, placebo-controlled parallel group study performed at three centers. The patients who fulfilled Rome II Criteria of IBS were included in the study. A total of 180 patients with IBS were randomized to drotaverine and placebo tre...

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

    Directory of Open Access Journals (Sweden)

    Andrew J. Butler

    2015-01-01

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

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

    Science.gov (United States)

    Butler, Andrew J.; Kallos, Justiss; Housley, Stephen N.; LaPlaca, Michelle C.; Traynelis, Stephen F.; Wolf, Steven L.

    2015-01-01

    Stroke is a leading cause of death and disability in the USA. Up to 60% of patients do not fully recover despite intensive physical therapy treatment. N-Methyl-D-aspartate receptors (NMDA-R) have been shown to play a role in synaptic plasticity when activated. D-Cycloserine promotes NMDA receptor function by binding to receptors with unoccupied glycine sites. These receptors are involved in learning and memory. We hypothesized that D-cycloserine, when combined with robotic-assisted physiotherapy (RAP), would result in greater gains compared with placebo + RAP in stroke survivors. Participants (n = 14) were randomized to D-cycloserine plus RAP or placebo plus RAP. Functional, cognitive, and quality-of-life measures were used to assess recovery. There was significant improvement in grip strength of the affected hand within both groups from baseline to 3 weeks (95% confidence interval for mean change, 3.95 ± 2.96 to 4.90 ± 3.56 N for D-cycloserine and 5.72 ± 3.98 to 8.44 ± 4.90 N for control). SIS mood domain showed improvement for both groups (95% confidence interval for mean change, 72.6 ± 16.3 to 82.9 ± 10.9 for D-cycloserine and 82.9 ± 13.5 to 90.3 ± 9.9 for control). This preliminary study does not provide evidence that D-cycloserine can provide greater gains in learning compared with placebo for stroke survivors. PMID:26587287

  5. Low Intensity laser therapy in patients with burning mouth syndrome: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Norberto Nobuo SUGAYA

    Full Text Available Abstract The aim of this study was to assess the effectiveness of low intensity laser therapy in patients with Burning Mouth Syndrome (BMS. Thirty BMS subjects were randomized into two groups – Laser (LG and Placebo (CG. Seven patients dropped out, leaving 13 patients in LG and 10 patients in CG. Each patient received 4 irradiations (laser or placebo twice a week, for two consecutive weeks (blinded to the type of irradiation received. Infrared laser (AsGaAI irradiations were applied to the affected mucosa in scanning mode, wavelength of 790 nm, output power of 20 mW and fluence of 6 J/cm2. A visual analogue scale (VAS was used to assess the therapeutic effect before and after each irradiation, and at all the control time periods: 7, 14, 30, 60 and 90 days after the last irradiation. One researcher delivered irradiation and another recorded the results. Both researchers were blinded, the first to the results, and the second to the type of radiation applied. The results were categorized according to the percentage of symptom level variation, and showed a statistically better response in LG in only two categories of the control checkpoints (p=0.02; Fisher’s Exact Test. According to the protocol used in this study, low intensity laser therapy is as beneficial to patients with BMS as placebo treatment, indicating a great emotional component of involvement in BMS symptomatology. Nevertheless, there were positive results in some statistical analyses, thus encouraging further research in BMS laser therapy with other irradiation parameters.

  6. Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Geannyne Villegas-Rivera

    2015-01-01

    Full Text Available Objective. To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV and rosuvastatin (ROSUV on oxidative stress (OS markers in patients with diabetic polyneuropathy (DPN. Methods. We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM and DPN, as evaluated by composite scores and nerve conduction studies (NCS. Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO, and nitric oxide (NO surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis. Results. LPO levels were reduced in both statin arms after 16 weeks of treatment (p<0.05 versus baseline, without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores. Discussion. EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.

  7. Randomized double blind placebo control studies, the "Gold Standard" in intervention based studies

    Directory of Open Access Journals (Sweden)

    Shobha Misra

    2012-01-01

    Full Text Available Studies follow a hierarchy in terms of the quality of evidence that they can provide. Randomized double blind placebo control (RDBPC studies are considered the "gold standard" of epidemiologic studies. And the same is discussed at length in this paper taking example of a real journal article employing this study design to answer the research question; "Does once daily dose of Valacyclovir reduce the risk of transmission of genital herpes in a susceptible partner?" RDBPC studies remain the most convincing research design in which randomly assigning the intervention can eliminate the influence of unknown or immeasurable confounding variables that may otherwise lead to biased and incorrect estimate of treatment effect. Also, randomization eliminates confounding by baseline variables and blinding eliminates confounding by co-interventions, thus eliminating the possibility that the observed effects of intervention are due to differential use of other treatments. The best comparison is placebo control that allows participants, investigators and study staff to be blinded. The advantage of trial over an observational study is the ability to demonstrate causality. Hope, this will be useful to neophyte researchers to understand causal hierarchy when critically evaluating epidemiologic literature.

  8. Randomized double blind placebo control studies, the "Gold Standard" in intervention based studies.

    Science.gov (United States)

    Misra, Shobha

    2012-07-01

    Studies follow a hierarchy in terms of the quality of evidence that they can provide. Randomized double blind placebo control (RDBPC) studies are considered the "gold standard" of epidemiologic studies. And the same is discussed at length in this paper taking example of a real journal article employing this study design to answer the research question; "Does once daily dose of Valacyclovir reduce the risk of transmission of genital herpes in a susceptible partner?" RDBPC studies remain the most convincing research design in which randomly assigning the intervention can eliminate the influence of unknown or immeasurable confounding variables that may otherwise lead to biased and incorrect estimate of treatment effect. Also, randomization eliminates confounding by baseline variables and blinding eliminates confounding by co-interventions, thus eliminating the possibility that the observed effects of intervention are due to differential use of other treatments. The best comparison is placebo control that allows participants, investigators and study staff to be blinded. The advantage of trial over an observational study is the ability to demonstrate causality. Hope, this will be useful to neophyte researchers to understand causal hierarchy when critically evaluating epidemiologic literature.

  9. Oxiracetam in dementia: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Bottini, G; Vallar, G; Cappa, S; Monza, G C; Scarpini, E; Baron, P; Cheldi, A; Scarlato, G

    1992-09-01

    A multicentre, double-blind, between-patient study was carried out to evaluate the efficacy and tolerability of oxiracetam (800 mg tablet), in comparison with placebo, each given twice daily for 12 weeks to patients suffering from primary degenerative, multi-infarct or mixed dementia. Efficacy was assessed by a neuropsychological battery (simple reaction time, controlled associations, short story, Raven's Progressive Matrices, token test, digit span, word list learning), administered at the beginning and at the end of the study, and by a quality of life scale, administered at entry and after 6 and 12 weeks treatment. Sixty-five patients (28 men, 37 women, mean age 71 yrs) were enrolled; 58 completed the study: 2 on oxiracetam were withdrawn because of poor tolerability, 2 (one in each group) were withdrawn for poor compliance, one (on oxiracetam) for the occurrence of a transient ischaemic attack (defined as not related to the treatment) and 2 for administrative reasons. A significantly (p < 0.01) different effect in favour of oxiracetam was observed on the quality of life scale, and confirmed by significant (defined according to the Bonferroni technique) differences in some neuropsychological tests (e.g. controlled associations, short story). Four patients in the oxiracetam group complained of a total of 5 unwanted effects, and 1 on placebo complained of 3 unwanted effects, but none of them was withdrawn from the study.

  10. Acetylcysteine in the treatment of subacute sinusitis: A double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Bahtouee, Mehrzad; Monavarsadegh, Gholamhosein; Ahmadipour, Mohammadjavad; Motieilangroodi, Mazyar; Motamed, Niloofar; Saberifard, Jamshid; Eghbali, Seyyedsajjad; Adibi, Hooman; Maneshi, Hesam; Malekizadeh, Hasan

    2017-01-01

    Sinusitis is a common disease with harmful effects on the health and finances of patients and the economy of the community. It is easily treated in most of its acute stages but is associated with some management difficulties as it goes toward chronicity. Therefore, we tried to improve the treatment of subacute sinusitis by using acetylcysteine, which is a safe mucolytic and antioxidant agent. Thirty-nine adult patients with subacute sinusitis proved by computed tomography (CT) were enrolled in a double-blind, placebo-controlled trial. They received oral amoxicillin-clavulanic acid and normal saline nasal drops for 10 days and oral pseudoephedrine for 7 days. In addition, the patients received acetylcysteine (600 mg orally, once daily) in the intervention group or placebo in the control group for 10 days. A paranasal CT scan was taken at baseline and 30 days after patients finished the treatment and was evaluated quantitatively by Lund-Mackay (LM) score. Symptoms and some aspects of quality of life also were assessed at baseline and 14 days after initiation and 30 days after termination of the treatment via the Sino-Nasal Outcome Test questionnaire. The groups showed no significant difference in LM score after treatment. A positive correlation was observed between the LM and SNOT-20 scores. We concluded that adding oral acetylcysteine to amoxicillin-clavulanic acid, pseudoephedrine, and intranasal normal saline has no benefit for the treatment of subacute sinusitis.

  11. A randomized, double-blind, placebo-controlled, parallel-group study of rufinamide as adjunctive therapy for refractory partial-onset seizures.

    Science.gov (United States)

    Biton, Victor; Krauss, Gregory; Vasquez-Santana, Blanca; Bibbiani, Francesco; Mann, Allison; Perdomo, Carlos; Narurkar, Milind

    2011-02-01

    Efficacy and safety of adjunctive rufinamide (3,200 mg/day) was assessed in adolescents and adults with inadequately controlled partial-onset seizures receiving maintenance therapy with up to three antiepileptic drugs (AEDs). This randomized, double-blind, placebo-controlled, parallel-group, multicenter study comprised a 56-day baseline phase (BP), 12-day titration phase, and 84-day maintenance phase (MP). The primary efficacy variable was percentage change in total partial seizure frequency per 28 days (MP vs. BP). Secondary efficacy outcome measures included ≥50% responder rate and reduction in mean total partial seizure frequency during the MP. Safety and tolerability evaluation included adverse events (AEs), physical and neurologic examinations, and laboratory values. Pharmacokinetic and pharmacodynamic assessments were conducted. Three hundred fifty-seven patients were randomized: 176 to rufinamide and 181 to placebo. Patients had a median of 13.3 seizures per 28 days during BP; 86% were receiving ≥2 AEDs. For the intent-to-treat population, the median percentage reduction in total partial seizure frequency per 28 days was 23.25 for rufinamide versus 9.80 for placebo (p = 0.007). Rufinamide-treated patients were more than twice as likely to have had a ≥50% reduction in partial seizure frequency (32.5% vs. 14.3%; p < 0.001) and had a greater reduction in median total partial seizure rate per 28 days during the MP (13.2 vs. 5.2; p < 0.001). Treatment-emergent AEs occurring at ≥5% higher incidence in the rufinamide group compared with placebo were dizziness, fatigue, nausea, somnolence, and diplopia. Adjunctive treatment with rufinamide reduced total partial seizures in refractory patients. AEs reported were consistent with the known tolerability profile of rufinamide. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  12. Randomized, double-blind, placebo-controlled trial using lidocaine patch 5% in traumatic rib fractures.

    Science.gov (United States)

    Ingalls, Nichole K; Horton, Zachary A; Bettendorf, Matthew; Frye, Ira; Rodriguez, Carlos

    2010-02-01

    The lidocaine patch 5% was developed to treat postherpetic neuralgia. Anecdotal experience at our institution suggests the lidocaine patch 5% decreases narcotic usage in patients with traumatic rib fractures. This trial was developed to define the patch's efficacy. Patients with rib fractures admitted to the trauma service at our Level I trauma center were enrolled and randomized in a 1 to 1 double-blind manner to receive a lidocaine patch 5% or placebo patch. Fifty-eight patients who met the inclusion criteria were enrolled from January 2007 to August 2008. Demographic and clinical information were recorded. The primary outcomes variable was total narcotic use, analyzed using the 1-tailed Mann-Whitney test. The secondary outcomes variables included non-narcotic pain medication, average pain score, pulmonary complications, and length of stay. Significance was defined based on a 1-sided test for the primary outcome and 2-sided tests for other comparisons, at p rib fractures, gender, trauma mechanism, preinjury lung disease, smoking history, percent of current smokers, and need for placement of chest tube between the lidocaine patch 5% and placebo groups. There was no difference between the lidocaine patch 5% and placebo groups, respectively, with regard to total IV narcotic usage: median, 0.23 units versus 0.26 units; total oral narcotics: median, 4 units versus 7 units; pain score: 5.6 +/- 0.4 versus 6.0 +/- 0.3 (mean +/- SEM); length of stay: 7.8 +/- 1.1 versus 6.2 +/- 0.7; or percentage of patients with pulmonary complications: 72.7% versus 72.0%. The lidocaine patch 5% does not significantly improve pain control in polytrauma patients with traumatic rib fractures.

  13. 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

  14. Pimecrolimus versus Placebo in Minor, Recurrent Aphthous Stomatitis: A Randomized Double-blind Controlled Trial

    Directory of Open Access Journals (Sweden)

    Ayda Moghaddas

    2015-10-01

    Full Text Available Background: Oral aphthous is one of the most common oral mucosal inflammatory disorders which are very painful. There is no definite medical strategy up to now for aphthous treatment. Recently, some researchers have focused on immunomodulatory drugs such as tacrolimus and pimecrolimus in preventing aphthus recurrences. The aim of this study is to assess the effect of pimecrolimus cream against placebo in management of oral minor aphthous.Methods: The study is a randomized clinical trial, was done in “Shariati” hospital and Isfahan Skin Research Center. 62 patients with minor aphthuos were included and divided randomly to two groups (31 in each. In experimental group, pimecrolimus cream was applied for two weeks and cold cream for the same duration in control group. Patients were followed for 3 and one week; results were assessed in recovery after drug administration. Compared variables between two groups were including: the size of lesions, the time to recovery and pain intensity.Results: Results showed that mean size lesion in experimental and placebo group after complete recovery reduced (23.6 ±15.3 and 24.8 ±15 mm respectively but it was not significant (P: 0.1. Mean time for recovery in both groups was 8±2.2 and 9.5±2.5 respectively which was significant in pimecrolimus treated patients (P: 0.014. Also mean degree for pain intensity measured by pain scale method was reduced significantly in test group (6 ± 1.2 before treatment and 5.3 ± 1.1 after treatment, P<0.001.Conclusion: This study stated that pimecrolimus cream has an appropriate effect in reduction of recovery time and pain in minor aphthous compared to placebo but more clinical studies are needed to better conclusion.

  15. Mentha longifolia syrup in secondary amenorrhea: a double-blind, placebo-controlled, randomized trials

    Directory of Open Access Journals (Sweden)

    Mokaberinejad Roshanak

    2012-12-01

    Full Text Available Abstract Background Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea. Methods A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks, the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study. Results The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p Mentha longifolia L. syrup. Conclusion In conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea.

  16. 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

  17. Flumazenil, a Benzodiazepine Receptor Anatagonist, in the Reversal of Conscious Sedation following Gastroscopy. A Placebo Controlled, Dose Finding Study

    Directory of Open Access Journals (Sweden)

    Lloyd Sutherland

    1991-01-01

    Full Text Available Tim double-blind, placebo controlled, study assessed the efficacy and safety of flumazenil, a benzodiazepine antagonist, in reversing diazepam-induced sedation in 60 patients undergoing endoscopy. Patients were randomly assigned to one of six treatment groups (placebo, 5, 10, 15, 20 or 25 μg/kg flumazenil. Patient psychomotor function was determined using four standard assessments – Trieger, digit substitution, track tracing and cancellation tests. Flumazenil was well tolerated by all patients. All doses of Flumazenil were superior to placebo in reversing sedation. No significant differences were detected between the various treatment groups. Forty-five minutes after the flumazenil infusion, there were no differences between flumazenil- and placebo-treated patients in psychomotor function. Flumazenil is a safe, effective medication which reverses diazepam-induced conscious sedation. For most patients 0.5 mg given intravenously will reverse sedation.

  18. Acute Dietary Nitrate Supplementation and Exercise Performance in COPD: A Double-Blind, Placebo-Controlled, Randomised Controlled Pilot Study.

    Directory of Open Access Journals (Sweden)

    Katrina J Curtis

    Full Text Available Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD.We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9 mmoles nitrate or placebo (nitrate-depleted beetroot juice 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage.21 subjects successfully completed the study (age 68 ± 7 years; BMI 25.2 ± 5.5 kg/m2; FEV1 percentage predicted 50.1 ± 21.6%; peak VO2 18.0 ± 5.9 ml/min/kg. Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7 ± 8 mmHg nitrate vs. -1 ± 8 mmHg placebo; p = 0.008. Median endurance time did not differ significantly; nitrate 5.65 (3.90-10.40 minutes vs. placebo 6.40 (4.01-9.67 minutes (p = 0.50. However, isotime oxygen consumption (VO2 was lower following nitrate supplementation (16.6 ± 6.0 ml/min/kg nitrate vs. 17.2 ± 6.0 ml/min/kg placebo; p = 0.043, and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve.Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype.ISRCTN Registry ISRCTN66099139.

  19. Phase control of excitable systems

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano, S; Seoane, J M; Marino, I P; Sanjuan, M A F [Nonlinear Dynamics and Chaos Group, Departamento de Fisica, Universidad Rey Juan Carlos, Tulipan s/n, 28933 Mostoles, Madrid (Spain); Euzzor, S; Meucci, R; Arecchi, F T [CNR-Istituto Nazionale di Ottica Applicata, Largo E. Fermi, 6 50125 Firenze (Italy)], E-mail: samuel.zambrano@urjc.es, E-mail: jesus.seoane@urjc.es, E-mail: ines.perez@urjc.es

    2008-07-15

    Here we study how to control the dynamics of excitable systems by using the phase control technique. Excitable systems are relevant in neuronal dynamics and therefore this method might have important applications. We use the periodically driven FitzHugh-Nagumo (FHN) model, which displays both spiking and non-spiking behaviours in chaotic or periodic regimes. The phase control technique consists of applying a harmonic perturbation with a suitable phase {phi} that we adjust in search of different behaviours of the FHN dynamics. We compare our numerical results with experimental measurements performed on an electronic circuit and find good agreement between them. This method might be useful for a better understanding of excitable systems and different phenomena in neuronal dynamics.

  20. Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Jin, Sang-Man; Han, Kyung Ah; Yu, Jae Myung; Sohn, Tae Seo; Choi, Sung Hee; Chung, Choon Hee; Park, Ie Byung; Rhee, Eun Jung; Baik, Sei Hyun; Park, Tae Sun; Lee, In-Kyu; Ko, Seung-Hyun; Hwang, You-Cheol; Cha, Bong Soo; Lee, Hyoung Woo; Nam, Moon-Suk; Lee, Moon-Kyu

    2016-10-01

    To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion. © 2016 American Heart Association, Inc.

  1. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial.

    Science.gov (United States)

    Falanga, V; Fujitani, R M; Diaz, C; Hunter, G; Jorizzo, J; Lawrence, P F; Lee, B Y; Menzoian, J O; Tretbar, L L; Holloway, G A; Hoballah, J; Seabrook, G R; McMillan, D E; Wolf, W

    1999-01-01

    Several small studies have indicated that the systemic administration of pentoxifylline may accelerate healing of venous leg ulcers. The goal of this study was to further evaluate these findings in a larger scale placebo controlled trial and to explore the effect of the dose of pentoxifylline on healing. The study used a prospective, randomized, double-blind, parallel group placebo controlled design in a multicenter outpatient setting. Patients with one or more venous ulcer were enrolled, with all patients receiving standardized compression bandaging for treatment for their ulcers. Patients were also randomized to receive either pentoxifylline 400 mg, pentoxifylline 800 mg (two 400 mg tablets), or placebo tablets three times a day for up to 24 weeks. The main outcome measure was time to complete healing of all leg ulcers, using life table analysis. The study was completed as planned in 131 patients. Patients receiving 800 mg three times a day of pentoxifylline healed faster than placebo (p = 0.043, Wilcoxon test). The median time to complete healing was 100, 83, and 71 days for placebo, pentoxifylline 400 mg, and pentoxifylline 800 mg three times a day, respectively. Over half of all patients were ulcer free at week 16 (placebo) and at week 12 in both pentoxifylline groups. Whereas the placebo group had only achieved complete healing in half of the cases by week 16, all of the subjects remaining in the group receiving the high dose of pentoxifylline had healed completely. Treatment with pentoxifylline was well tolerated with similar drop-out rates in all three treatment groups. Complete wound closure occurred at least 4 weeks earlier in the majority of patients treated with pentoxifylline by comparison to placebo. A higher dose of pentoxifylline (800 mg three times a day) was more effective than the lower dose. We conclude that pentoxifylline is effective in accelerating healing of leg ulcers.

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

    Directory of Open Access Journals (Sweden)

    Matthias Huber

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

  3. Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

    Science.gov (United States)

    Joy, Tisha R; McKenzie, Charles A; Tirona, Rommel G; Summers, Kelly; Seney, Shannon; Chakrabarti, Subrata; Malhotra, Neel; Beaton, Melanie D

    2017-01-01

    AIM To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH). METHODS Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy. RESULTS Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol

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

    Science.gov (United States)

    Shen, Chwan-Li; Chyu, Ming-Chien; Yeh, James K; Felton, Carol K; Xu, Ke T; Pence, Barbara C; Wang, Jia-Sheng

    2009-09-04

    effect error terms was applied. Traditional procedures such as ANCOVA, chi-squared analysis, and regression were used for comparisons. 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.

  5. 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

  6. Mentha Longifolia Syrup in Secondary Amenorrhea: a Double-blind, Placebo-Controlled, Randomized Trials

    Directory of Open Access Journals (Sweden)

    Roshanak Mokaberinejad

    2012-12-01

    Full Text Available Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea.Methods A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks, the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study.Results The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p < 0.001. The regularity of bleeding throughout the study was markedly better in the drug group compared with those given placebo (33.3% vs. 3.3%; p < 0.001. No notable complication or side effect was reported in relation to Mentha longifolia L. syrup.ConclusionIn conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea.

  7. Mentha longifolia syrup in secondary amenorrhea: a double-blind, placebo-controlled, randomized trials

    Science.gov (United States)

    2012-01-01

    Background Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea. Methods A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day) for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks), the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no) of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study. Results The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p < 0.001). The regularity of bleeding throughout the study was markedly better in the drug group compared with those given placebo (33.3% vs. 3.3%; p < 0.001). No notable complication or side effect was reported in relation to Mentha longifolia L. syrup. Conclusion In conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea. PMID

  8. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Whitlock, Richard P; Devereaux, P J; Teoh, Kevin H; Lamy, Andre; Vincent, Jessica; Pogue, Janice; Paparella, Domenico; Sessler, Daniel I; Karthikeyan, Ganesan; Villar, Juan Carlos; Zuo, Yunxia; Avezum, Álvaro; Quantz, Mackenzie; Tagarakis, Georgios I; Shah, Pallav J; Abbasi, Seyed Hesameddin; Zheng, Hong; Pettit, Shirley; Chrolavicius, Susan; Yusuf, Salim

    2015-09-26

    Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388. Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared

  9. Fluoxetine Treatment for Prevention of Relapse of Depression in Children and Adolescents: A Double-Blind, Placebo-Controlled Study

    Science.gov (United States)

    Emslie, Graham J.; Heiligenstein, John H.; Hoog, Sharon L.; Wagner, Karen Dineen; Findling, Robert L.; McCracken, James T.; Nilsson, Mary E.; Jacobson, Jennie G.

    2004-01-01

    Objective: To compare fluoxetine 20 to 60 mg/day with placebo for prevention of relapse of major depressive disorder in children and adolescents who had achieved Children's Depression Rating Scale, Revised scores of [less than or equal to]28 during treatment with fluoxetine 20 to 60 mg. Method: In this 32-week relapse-prevention phase of a…

  10. Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bone Kerry M

    2009-06-01

    Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

  11. Placebo Effect

    Science.gov (United States)

    ... C. Spencer, MD Steven Karceski, MD The placebo effect Joseph H. Friedman, MD Richard Dubinsky, MD WHAT ... placebo: a “dummy” medication that should have no effect on the condition. Placebos are not only drugs. ...

  12. Ethics of Placebo Control in Trials for Idiopathic Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Maldonado Fernández, Miguel; Kornetsky, Susan; Rubio Rodriguez, Laura

    2016-07-01

    Idiopathic sudden sensorineural hearing loss (ISSHL) involves sudden loss of hearing from cochlear or retrocochlear origin of unknown cause. Systemic corticosteroids may be considered in the management of ISSNHL. However, an updated Cochrane systematic review concludes that "the value of steroids in the treatment of idiopathic sudden sensorineural hearing loss remains unclear since the evidence obtained from randomized controlled trials is contradictory in outcome." Therefore, a new clinical trial that addresses this question is mandatory. A first step in its design is to determine if placebo control would be ethically acceptable. We conclude that there is equipoise (uncertainty) about the use of corticosteroids for ISSHL. A new trial is justified-but with the inclusion of interim analyses to detect early imbalances on efficacy or safety and with the ability to stop the trial if needed. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  13. 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

  14. Smectite in acute diarrhea in children: a double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Madkour, A A; Madina, E M; el-Azzouni, O E; Amer, M A; el-Walili, T M; Abbass, T

    1993-08-01

    Dioctahedral smectite (DS) a natural adsorbent clay capable of adsorbing viruses, bacteria, and other intestinal irritants in vitro, is claimed to possess beneficial "antidiarrheal" properties. This study tested the effect of DS on the duration of diarrhea and the frequency and amount of liquid stools. Ninety well-nourished boys, aged 3-24 months, with acute watery diarrhea and mild, moderate, or severe dehydration were included in a randomized double-blind, placebo-controlled trial. After initial rehydration, they received DS or placebo (1.5 g freshly dissolved in 50 ml of water, four times daily for 3 days) along with oral rehydration solution (ORS) and adequate feeding. The clinical characteristics of both groups were comparable on admission. Patients in the smectite group had a significantly shorter duration of diarrhea (mean +/- SD, 54 +/- 16 vs. 73 +/- 13 h) and significantly fewer stools (2.6 +/- 0.8 vs. 3 +/- 0.7 on second day; 1.9 +/- 0.7 vs. 2.4 +/- 0.7 on third day; and 11.3 +/- 3.2 vs. 13.8 +/- 3 overall). The amount of liquid stools was not significantly reduced. Weight gain at 24, 48, and 72 h and on recovery was significantly higher in the smectite group despite the comparable fluid and food intake in both groups. These results suggest a beneficial effect of DS in shortening the duration of diarrhea and reducing the frequency of liquid stools in children rehydrated with ORS.

  15. Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.

    Science.gov (United States)

    Riche, Daniel M; Riche, Krista D; Blackshear, Chad T; McEwen, Corey L; Sherman, Justin J; Wofford, Marion R; Griswold, Michael E

    2014-01-01

    Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL ≥ 100 mg/dL. Subjects were divided into four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6-8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001) which was not seen with GE combination (P = 0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (-7.8 mmHg; P < 0.01) and diastolic blood pressure (-7.3 mmHg; P < 0.001) were reduced with high dose pterostilbene. Patients not on cholesterol medication (n = 51) exhibited minor weight loss with pterostilbene (-0.62 kg/m(2); P = 0.012). Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227.

  16. Pterostilbene on Metabolic Parameters: A Randomized, Double-Blind, and Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Daniel M. Riche

    2014-01-01

    Full Text Available Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL≥100 mg/dL. Subjects were divided into four groups: (1 pterostilbene 125 mg twice daily; (2 pterostilbene 50 mg twice daily; (3 pterostilbene 50 mg + grape extract (GE 100 mg twice daily; (4 matching placebo twice daily for 6–8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P=0.001 which was not seen with GE combination (P=0.47. Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (−7.8 mmHg; P<0.01 and diastolic blood pressure (−7.3 mmHg; P<0.001 were reduced with high dose pterostilbene. Patients not on cholesterol medication (n=51 exhibited minor weight loss with pterostilbene (−0.62 kg/m2; P=0.012. Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227.

  17. A multicenter,double-blind, placebo-controlled, randomized, phase Ⅲ clinical study of etanercept in treatment of ankylosing spondylitis%依那西普治疗强直性脊柱炎的多中心、随机、双盲、安慰剂对照临床研究

    Institute of Scientific and Technical Information of China (English)

    黄烽; 吕良敬; 杨尊明; 张洁; 黄建林; 吴东海; 栗占国; 陈顺乐; 潘云峰; 马丽; 陈适

    2010-01-01

    Objective To evaluate the short-term efficacy and safety of etanercept treatment in Chinese patients with active ankylosing spondylitis ( AS ). Methods This was a 12-week multicenter,double-blind, placebo-controlled, randomized phase Ⅲ clinical study. The first part was a 6-week placebocontrolled period followed by a 6-week open-label period. The primary efficacy endpoint was the percentage of subjects achieving a 20% improvement in assessment in ankylosing spondylitis (ASAS) ( ASAS 20). The secondary efficacy endpoints were the percentage of patients achieving a 40% improvement in ASAS (ASAS 40), achieving a 50% improvement in ASAS( ASAS 50), achieving a 70% improvement in ASAS (ASAS 70), and ASAS 5/6 responses at all visits, and the improvement in subject global assessment,physician global assessment, nocturnal and total back pain, bath AS functional index ( BASFI ), bath AS disease activity index (BASDAI), spinal mobility, joint assessment and quality of life assessment. All subjects in the study were evaluated for safety. Results The primary endpoint, ASAS 20 at week 6, was achieved by 86. 5% (64/74) patients in the etanercept group compared to 29. 5% (23/78) patients in the placebo group(P <0. 001 ). As early as week 2, the percentages of patients achieving the ASAS 20 between the two groups were significantly different. Furthermore, the majority of secondary efficacy end points were also significantly improved. Most of adverse events (AE) were mild in nature, the commonest adverse events were elevated liver function levels, injection site reactions and nasopharyngitis. No death or serious AE were observed. Conclusion Etanercept can improve symptoms fastly,significantly and safely in Chinese patients with active AS.%目的 评价依那西普治疗活动性强直性脊柱炎(AS)的短期疗效与安全性.方法 为期12周(双盲治疗期和开放治疗期各6周)的随机、双盲、安慰剂对照的Ⅲ期临床研究.双盲期试验组和对照组患

  18. Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Fanaei, Hamed; Khayat, Samira; Kasaeian, Amir; Javadimehr, Mani

    2016-04-01

    Premenstrual syndrome (PMS) is a variety of physical, mental, and behavioral symptoms that start during the late luteal phase of the menstrual cycle, and the symptoms disappear after the onset of menses. Serum brain-derived neurotrophic factor (BDNF) levels during luteal phase in women associated with PMS have more alterations than women not suffering from PMS. In this regard, altered luteal BDNF levels in women with PMS might play a role in a set of psychological and somatic symptoms of the PMS. Studies of last decade revealed neuroprotective effects of curcumin and its ability to increase BDNF levels. In the present study, we evaluated the effect of curcumin on serum BDNF level and PMS symptoms severity in women with PMS. Present study is a Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Curcumin treatment was given for three successive menstrual cycles and each cycle ran 10 days. After having identified persons with PMS, participants were randomly allocated into placebo (n=35) and curcumin (n=35) groups. Each sample in placebo and curcumin groups received two capsules daily for seven days before menstruation and for three days after menstruation for three successive menstrual cycles. Participants noted the severity of the symptoms mentioned in the daily record questionnaire. Self-report was used to determine menstrual cycle phase of participants. At the fourth day of each menstrual cycle venous blood samples were collected for BDNF measurement by ELISA method. Before intervention, BDNF levels and mean scores of PMS symptoms (mood, behavioral and physical symptoms) between two groups showed no significant differences. But in curcumin group first, second and third cycles after interventions BDNF levels were significantly higher and mean scores of PMS symptoms were significantly less than placebo group. Based on our results part of these beneficial effects of curcumin may be mediated through enhancing serum BDNF levels in women with PMS.

  19. Efficacy of betamethasone valerate medicated plaster on painful chronic elbow tendinopathy: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Frizziero, Antonio; Causero, Araldo; Bernasconi, Stefano; Papalia, Rocco; Longo, Mario; Sessa, Vincenzo; Sadile, Francesco; Greco, Pasquale; Tarantino, Umberto; Masiero, Stefano; Rovati, Stefano; Frangione, Valeria

    2016-01-01

    to investigate the efficacy and safety of a medicated plaster containing betamethasone valerate (BMV) 2.25 mg in patients with chronic elbow tendinopathy. randomized, double-blind, placebo-controlled study with assignment 2:2:1:1 to BMV medicated plaster applied daily for 12 hours, daily for 24 hours or matched placebo. 62 patients aged ≥18 years with chronic lateral elbow tendinopathy were randomized. The primary efficacy variable was pain reduction (VAS) at day 28. Secondary objectives included summed pain intensity differences (SPID), overall treatment efficacy and tolerability. mean reduction in VAS pain score at day 28 was greater in both BMV medicated plaster groups, -39.35±27.69 mm for BMV12-h and -36.91±32.50 mm for BMV24-h, than with placebo, -20.20±27.32 mm. Considering the adjusted mean decreases, there was a statistically significant difference between BMV12-h and placebo (p=0.0110). Global pain relief (SPID) and overall treatment efficacy were significantly better with BMV. BMV and placebo plasters had similar local tolerability and there were few treatment-related adverse events. BMV plaster was significantly more effective than placebo at reducing pain in patients with chronic elbow tendinopathies. The BMV plaster was safe and well tolerated.

  20. Effect of hyoscine-N-butyl bromide rectal suppository on labor progress in primigravid women: a randomized double-blind placebo-controlled clinical trial

    Science.gov (United States)

    Makvandi, Somayeh; Tadayon, Mitra; Abbaspour, Mohammadreza

    2011-01-01

    Aim To determine the effects of hyoscine-N-butyl bromide (HBB) rectal suppository on labor progress in primigravid women. Methods A randomized double-blind placebo-controlled clinical trial was carried out on 130 primigravid women admitted for spontaneous labor. The women were recruited based on the inclusion and exclusion criteria and randomized into the experimental (n = 65) and control group (n = 65). In the beginning of the active phase of labor, 20 mg of HBB rectal suppository was administered to the experimental group, while a placebo suppository was administered to the control group. Cervical dilatation and duration of active phase and second stage of labor were recorded. Results The rate of cervical dilatation was 2.6 cm/h in the experimental and 1.5 cm/h in the control group (P suppository in the active management of labor can shorten both the active phase and second stage of labor without significant side-effects. Registration No IRCT138804282204N1. PMID:21495198

  1. A randomised placebo-controlled trial of a traditional Chinese herbal formula in the treatment of primary dysmenorrhoea.

    Directory of Open Access Journals (Sweden)

    Lan Lan Liang Yeh

    Full Text Available BACKGROUND: Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial. METHODOLOGY/PRINCIPAL FINDINGS: A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow

  2. Long-term oral calcium supplementation reduces diastolic blood pressure in end stage renal disease. A randomized, double-blind, placebo controlled study.

    Science.gov (United States)

    Petersen, L J; Rudnicki, M; Højsted, J

    1994-01-01

    Previous studies suggest that oral calcium supply reduces blood pressure in patients with mild to moderate hypertension. The aim of this study was to determine whether oral calcium supply reduces blood pressure in patients undergoing haemodialysis. The study was randomized, double-blind, and placebo controlled. Eleven patients received two grams of calcium per day and 12 patients received placebo. Three patients (one from the calcium group and two from the placebo group) dropped out within the first month. The groups were comparable at inclusion regarding blood pressure, weight, and serum values. Blood pressure measurements were auscultatory with a mercury manometer and diastolic blood pressure was measured as Korotkoff phase V. At inclusion a significant positive correlation between serum phosphate and blood pressure was found. After a study period of six months a significant reduction in diastolic blood pressure was found between the two groups (p < 0.05), but no difference was found in systolic blood pressure. The reduction in diastolic blood pressure was 6.9 mmHg of the pretreatment level in the calcium group. In conclusion, the treatment of secondary hyperparathyroidism with oral calcium gives good benefits in the regulation of diastolic blood pressure. A well controlled phosphate homeostasis may also be of importance for the control of blood pressure in haemodialysis patients.

  3. Efficacy of minocycline in acute ischemic stroke: A single-blinded, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    M V Padma Srivastava

    2012-01-01

    Full Text Available Background: Minocycline is a semisynthetic derivative of the tetracycline group of antibiotics, which have neuroprotective effects. In animal stroke models, minocycline had shown promising evidence to improve clinical and functional outcomes. Objective: To analyze the effect of oral minocycline in acute ischemic stroke patients. Materials and Methods: This was a randomized single-blinded open-label study. The study group received oral minocycline 200 mg/day for 5 days and the control group received oral vitamin B capsules. Baseline assessment included the following: National Institute of Health Stroke Scale (NIHSS score, modified Barthel Index (mBI, modified Rankin Scale (mRS score, Magnetic Resonance Imaging (MRI of brain including Diffusion Weighted Imaging (DWI, chest X-ray, and routine laboratory investigations. The clinical scales were repeated at days 1, 7, and 30. The end point was outcomes at 3 months (90 days. Statistical analysis was done with SPSS 11.5 (P<0.05. Paired t-test and multiple-measures Analysis Of Variance (ANOVA were used. Results: Fifty patients with acute ischemic stroke were included in the study. Of these, 23 patients received minocycline and 27 patients received placebo i.e., vitamin B capsules. NIHSS score in patients receiving minocycline had shown statistically significant improvement at day 30 and 90 as compared with the controls. Similarly, mRS scores and BI showed significant improvement in patients receiving minocycline at three months as compared to the control group. No mortality, myocardial infarctions, recurrent strokes, and hemorrhagic transformations were noted in both groups. Conclusions: Patients with acute ischemic stroke had significantly better outcome with minocycline treatment as compared with those administered placebo. The above findings suggest that minocycline can be helpful in reducing the clinical deficits after acute ischemic stroke.

  4. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Klopstock, Thomas; Yu-Wai-Man, Patrick; Dimitriadis, Konstantinos; Rouleau, Jacinthe; Heck, Suzette; Bailie, Maura; Atawan, Alaa; Chattopadhyay, Sandip; Schubert, Marion; Garip, Aylin; Kernt, Marcus; Petraki, Diana; Rummey, Christian; Leinonen, Mika; Metz, Günther; Griffiths, Philip G; Meier, Thomas; Chinnery, Patrick F

    2011-09-01

    Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

  5. Doxepin is More Effective than Nortriptyline and Placebo for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Triple-Blind Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Ghadir M.D.

    2011-06-01

    Full Text Available Background: The current treatment of IBS is often unsatisfactory and frustrating. Several controlled trials have demonstrated benefits of tricyclic antidepressants for irritable bowel syndrome, especially when pain is a prominent symptom but the efficacy of antidepressants in irritable bowel syndrome is controversial. The aim of this study was to compare the effect of doxepin and nortriptyline on diarrhea-predominant irritable bowel syndrome.Methods: Seventy-five patients with IBS according to Rome III criteria were treated for two months. The patients were randomly assigned to one of three groups treated with doxepin, nortriptyline or placebo. Subjects were assessed clinically one month and two months after treatment. The symptoms and adverse effects of the drugs were recorded in the questionnaire. The total score was considered as the number of the symptoms for each patient, which ranged between zero and six.Results: Improvements in abdominal pain and bloating in the doxepin group were significantly higher than the nortriptyline or the placebo groups (P=0.001 and P=0.012, respectively. However, improvement in diarrhea in patients on nortriptyline was significantly higher than the other groups (P=0.018. The average improvement of symptoms in the patients after two months of treatment in doxepin, nortriptyline and placebo groups, respectively were 2.56, 2 and 0.6 (P<0.05.Conclusion: Both doxepin and nortriptyline are effective for the treatment of diarrhea-predominant irritable bowel syndrome in a period of two months but doxepin seems to be more efficacious than nortriptyline in this regard. However, larger comparative trials are suggested.

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

    Science.gov (United States)

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

    2007-07-01

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

  7. Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting Multiple Sclerosis Progression: Preliminary Findings of a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Vahid Shaygannejad

    2012-01-01

    Full Text Available The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS. A phase II double-blind placebo-controlled randomized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were randomly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy. Response to treatment was assessed at eight-week intervals. In both groups, the mean relapse rate decreased significantly (P<0.001. In the 25 patients treated with placebo, the mean (SD Expanded Disability Status Scale (EDSS increased from 1.70 (1.21 at baseline to 1.94 (1.41 at the end of study period (P<0.01. Average EDSS and relapse rate at the end of trial did not differ between groups. Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate. A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention.

  8. A Randomized Placebo-Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in Pervasive Development Disorders

    Science.gov (United States)

    2015-03-01

    Award Number: W81XWH-09-1-0091 TITLE: A Randomized Placebo -Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in...From - To) 1 Mar 2014 - 28 Feb 2015 4. TITLE AND SUBTITLE A Randomized Placebo -Controlled Trial of D-Cycloserine for the Enhancement of Social...adolescents (ages 5-11 years) with ASDs during a randomized placebo -controlled trial. The safety and tolerability of DCS and durability of

  9. [Analgesic efficacy of TENS therapy in patients with gonarthrosis. A prospective, randomised, placebo-controlled, double-blind study].

    Science.gov (United States)

    Gschiel, B; Kager, H; Pipam, W; Weichart, K; Likar, R

    2010-09-01

    The goal of the study was to substantiate the influence of TENS on pain development and medication needs of patients with proven gonarthrosis and chronic pain. The study included a 3-week stimulation period and 2-week observation period after the end of stimulation. Patients (at least 20 per group) were assigned to either an active treatment group or placebo group in a randomised, double-blind, placebo-controlled trial. For the active treatment group the TENS therapy device with HAN stimulation (alternating phase of stimulation) was used (TENStem eco).Total length of time: 30 min at least two times a day. The length of therapy was 3 weeks (therapy), followed by an observation period of 2 weeks (follow-up). The total length of the study was 5 weeks, whereby at the beginning and at the end of weeks 1, 3 and 5 the SF-36, WOMAC score and Lysholm score were documented; the pain score was documented daily. There are no significant demographic differences between the groups. In the active treatment group there was clear relief in pain intensity in the morning, midday and evening over the 3-week period of therapy. The Lysholm score in the active treatment group was 53.4 at the beginning, 90 after 1 week, 94.5 after the third week and 91 by the fifth week (significant difference). There were no side effects. TENS therapy with HAN stimulation resulted in pain relief in patients with gonarthrosis during the therapy period with TENS, but the pain relief did not last beyond the end of the TENS therapy. There was an improvement in the Lysholm score and the WOMAC score during the therapy. This improvement remained over the following 2-week period of observation without further TENS therapy. TENS therapy is a simple and effective method to treat gonarthrosis with very few side effects.

  10. Denosumab for treating periprosthetic osteolysis; study protocol for a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Sköldenberg, Olof; Rysinska, Agata; Eisler, Thomas; Salemyr, Mats; Bodén, Henrik; Muren, Olle

    2016-04-23

    Wear-induced osteolysis is the main factor in reducing the longevity of total hip arthroplasty (THA). The transmembrane Receptor Activator of Nuclear Factor κ B (RANK) and its corresponding ligand RANKL is an important regulator of osteoclast activity and bone resorption and is associated with osteolysis around implant. Inhibiting RANKL with denosumab is effective in vivo in preventing osteoporosis-related fractures. In vitro, osteoclasts can be blocked in animal models of osteolysis. We hypothesize that denosumab is effective in reducing wear-induced osteolysis around uncemented acetabular implants in THA. A randomized, double-blind, placebo-controlled trial will be conducted. We will include 110 patients, 40-85 years of age, with a known osteolytic lesion around an uncemented acetabular component ≥7 years after the primary operation. The patients will be randomized in a 1:1 ratio to subcutaneous injections of 60 mg denosumab or placebo for a total of 6 doses with start on day one and every 6 months with last treatment at 30 months. The primary endpoint will be the change in volume of the osteolytic lesion at 3 years measured with three-dimensional computed tomography (3D-CT). Secondary endpoints include functional outcome scores, change in bone mineral density of the lumbar spine, serological markers of bone turnover and adverse events. In vitro results of both bisphosphonates and RANKL inhibitors have been promising, showing reduced osteolysis with treatment. This is, to our knowledge, the first clinical trial testing the efficacy of denosumab in reducing wear-induced osteolysis. The study is an academic, phase II trial from an independent center and is designed to demonstrate efficacy in reducing volume of osteolytic lesions around a total hip arthroplasty. ClinicalTrials.gov (NCT02299817) 2014-11-20.

  11. A randomized, double-blind, placebo-controlled, multicenter study on sibutramine in over-weighted and obese subjects

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objectives To assess weight loss efficacy ,safety and tolerability of sibutramine in simple obese subjects.Methods Randomized, double-blind, placebo-controlled clinical trial. Four hospital outpatient clinics in Shanghai, Chongqing, Shandong and Tianjin, respectively. Participants: 233 men and women, 18-65 years old, with body mass index (BMI) ranging from 27 to 40*!kg/m2 were randomly divided into an intervened group and a placebo control group. Sibutramine 10 mg or placebo once a day. Main outcome measures: Body weight, routine laboratory and clinical safety monitoring.Results Of 233 eligible patients, 120 received sibutramine and 113 received placebo. Weight reduction was significantly greater in the intervened group (6.8±3.1) kg than the placebo control group (0.48±2.6) kg from week 4 onwards to week 24 (P<0.001). Some minor side effects were noticed in the subjects who took sibutramine. But the symptoms were light and short term. Sibutramine was will tolerated.Conclusions Sibutramine 10*!mg once a day is an effective an safe therapy for weight reduction in simple over-weighted and obese subjects.

  12. Estimating long-term effects of treatment from placebo-controlled trials with an extension period, using virtual twins.

    Science.gov (United States)

    Vittinghoff, Eric; McCulloch, Charles E; Woo, Claudine; Cummings, Steven R

    2010-05-10

    The best information about the benefits of long-term treatment is obtained from a long-term placebo-controlled trial. However, once efficacy has been demonstrated in relatively brief trials, it may not be possible to conduct long-term placebo-controlled trials, for ethical or practical reasons. This paper presents a method for estimating long-term effects of a treatment from a placebo-controlled trial in which some participants originally randomized to active-treatment volunteer to continue on treatment during an extension study, but follow-up of participants originally assigned to placebo ends with the trial, or they are crossed over to active treatment during the extension. We propose using data from the trial to project the outcomes for a 'virtual twin' for each active-treatment volunteer under the counterfactual placebo condition, and using bootstrap methods for inference. The proposed method is validated using simulation, and applied to data from the Fracture Intervention Trial and its extension, FLEX.

  13. Nonorganic insomnia in panic Disorder: comparative sleep laboratory studies with normal controls and placebo-controlled trials with alprazolam.

    Science.gov (United States)

    Saletu-Zyhlarz, Gerda M; Anderer, Peter; Berger, Peter; Gruber, Georg; Oberndorfer, Stefan; Saletu, Bernd

    2000-06-01

    Objective and subjective sleep and awakening quality was investigated in 11 drug-free patients (4 females, 7 males) aged 30-55 (mean: 44+/-9) years with nonorganic insomnia (F 51.0) related to panic disorder (F 41.0) as compared with 11 age- and sex-matched normal controls aged 30-58 (mean: 44+/-9) years, utilising polysomnography (PSG) and psychometry. PSG demonstrated decreased sleep efficiency (primary target variable), total sleep time (TST) and S2 as well as increased middle and late insomnia, S1, S3+S4, snoring and PLM in patients. There were no intergroup differences in REM variables. Subjective sleep quality deteriorated, as did drive and fine motor activity in the morning, while concentration increased. Blood pressure in the evening and morning and pulse rate in the evening were elevated. These differences as compared with normals were distinct from those observed in other sleep disorders. In a subsequent acute, placebo-controlled cross-over design study, patients received alprazolam 0.5 mg (Xanor((R));) and placebo. As compared with placebo, alprazolam induced an increase in sleep efficiency (primary target variable), TST and S2, a decrease in wakefulness during the total sleep period, S3+S4 and the oxygen desaturation and PLM indices, and improved subjective sleep quality, somatic complaints, drive, affectivity and drowsiness in the morning. There were no changes in REM variables. Thus, alprazolam induced changes that were opposite to the differences observed between patients and controls before treatment, thereby normalizing sleep and awakening quality. As observed in insomnia related to GAD and subsequent benzodiazepine therapy, the present study also points to a key-lock principle in the treatment of insomnia caused by anxiety disorders and neurophysiologically visualizes processes at the receptor level (e.g. benzodiazepine agonists versus inverse agonists). Copyright 2000 John Wiley & Sons, Ltd.

  14. Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Jørgensen, Erik; Wang, Yongzhong;

    2006-01-01

    BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy...

  15. Pentoxifylline Treatment in Severe Acute Pancreatitis: A Pilot, Double-Blind, Placebo-Controlled, Randomized Trial.

    Science.gov (United States)

    Vege, Santhi Swaroop; Atwal, Tegpal; Bi, Yan; Chari, Suresh T; Clemens, Magdalen A; Enders, Felicity T

    2015-08-01

    In acute pancreatitis (AP) tumor necrosis factor-α mediates multi-organ failure; in animal models its blockade with pentoxifylline ameliorates AP. The efficacy of pentoxifylline in predicted severe AP (pSAP) was tested in a double-blinded, randomized, control trial. Twenty-eight patients with pSAP were randomized within 72 hours of diagnosis to pentoxifylline or placebo. Baseline characteristics were similar in both groups. The pentoxifylline group had fewer intensive care unit admissions and shorter intensive care unit and hospital stays of longer than 4 days (all P < .05). Patients receiving pentoxifylline had no adverse effects. Pentoxifylline within 72 hours of pSAP is safe; a larger study of pentoxifylline in AP is needed to confirm efficacy. ClinicalTrials.gov number: NCT01292005. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. [Periprostatic anaesthesic infiltration for prostatic biopsy: a prospective, randomized, double blind and placebo-controlled study].

    Science.gov (United States)

    Valero, Gonzalo; González, E U Roxana

    2005-06-01

    A prospective, randomized, double blind and placebo-controlled study to evaluate the effectiveness of periprostatic infiltration with lidocaine to reduce pain of prostatic biopsy. In a thirteen months period of time, 115 patients were randomized to receive 10 ml of lidocaine 1% (n=60) or saline (n=55). Evaluating the pain with visual analogue scale (0-10), the first group referred average pain of 3.83 and the second group of 6.87, being this difference clearly significant (panesthesic puncture. The periprostatic infiltration is easy to perform without complications and it is effective in reducing the pain of this procedure. It should be used as a routine procedure in prostatic biopsy.

  17. Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence.

    Science.gov (United States)

    Schubiner, Howard; Saules, Karen K; Arfken, Cynthia L; Johanson, Chris-Ellyn; Schuster, Charles R; Lockhart, Nancy; Edwards, Ann; Donlin, Judy; Pihlgren, Eric

    2002-08-01

    In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP) versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder (ADHD) adults, the authors sought to determine whether MTP would be safe, control ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly greater ADHD symptom relief in the MTP group. There were no group differences in self-reported cocaine use, urinalysis results, or cocaine craving. Because of the relatively small sample size, the results are preliminary. However, we found that MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use while participants were in treatment.

  18. Randomised placebo controlled study on Sarasvata choorna in generalised anxiety disorder

    Directory of Open Access Journals (Sweden)

    Kshama Gupta

    2014-01-01

    Full Text Available Background: Generalised anxiety disorder (GAD is characterised by a pattern of frequent, persistent worry and anxiety, which is out of proportion to the impact of the event or circumstance that is the focus of the worry. GAD is associated with muscle tension, trembling, twitching, feeling shaky and muscle aches or soreness. Many individuals with GAD also experience somatic symptoms like sweating, nausea and diarrhoea. Epidemiological studies reveal that the prevalence rate of GAD in India is 5.8%. Objective: The main objective of the present study was to evaluate the efficacy of Sarasvata choorna in the management of GAD. Materials and Methods: In this study, a total of 114 patients with GAD satisfying the Diagnostic and Statistical Manual of Mental Disorders - Text Revision (DSM IV - TR diagnostic criteria were selected and randomly divided; of these, 102 patients completed the course of treatment. In trial group, Sarasvata choorna and in control group, placebo (wheat powder was given with the dose of 1 g thrice a day (i.e. 3 g/day along with madhu (honey and ghrita (cow′s ghee orally for 60 days. Fifteen days of follow up period was kept after treatment. Two assessments were done before and after treatment. Criterion of assessment was based on the scoring of Hamilton Anxiety Rating Scale (HAM-A. Paired and unpaired ′t′- test was used for statistical analysis. Results and Conclusion: In trial group (n = 51, 51.1% improvement and in control group (n = 51, 47.67% of improvement was observed with the significance of (P 0.05 was found in between the two groups. Sarasvata choorna did not provide better relief compared with placebo.

  19. 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

  20. TRIO-012: a multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer.

    Science.gov (United States)

    Mackey, John; Gelmon, Karen; Martin, Miguel; McCarthy, Nicole; Pinter, Tamas; Rupin, Mathieu; Youssoufian, Hagop

    2009-11-01

    In this multinational, placebo-controlled, randomized phase III trial, Translational Research In Oncology (TRIO) will define the efficacy and safety of adding a novel antiangiogenic agent, IMC-1121B (ramucirumab), to standard first-line docetaxel chemotherapy for women with HER2-negative metastatic breast cancer. We will evaluate whether the addition of IMC-1121B prolongs progression-free survival and whether its use improves overall survival. Accrual is under way.

  1. A pilot study on the impact of a low fructose diet and allopurinol on clinic blood pressure among overweight and prehypertensive subjects: a randomized placebo controlled trial.

    Science.gov (United States)

    Madero, Magdalena; Rodríguez Castellanos, Francisco E; Jalal, Diana; Villalobos-Martín, Maria; Salazar, Jonathan; Vazquez-Rangel, Armando; Johnson, Richard J; Sanchez-Lozada, L Gabriela

    2015-11-01

    Fructose and sodium intake have been associated with hypertension and metabolic syndrome. Although various mechanisms are involved, fructose causes hypertension partly through rising intracellular and serum uric acid. To date, there are no studies in adults that have evaluated the impact of low fructose diets and allopurinol on prehypertensive and overweight subjects. The objective of this study was to compare the effect of low fructose diet and allopurinol or placebo on blood pressure (BP) and metabolic syndrome components The study was a controlled clinical trial and consisted of two phases; in the first phase of intervention (4 weeks), patients were randomized to either low fructose diet (34 patients) or control diet (38 patients). In the second phase of intervention (weeks 4-8), the same groups continued with the same diet prescriptions but were further randomized to receive placebo or allopurinol (300 mg/d). Clinic and 24-hour ambulatory BP, anthropometric measures, and laboratory data were determined at baseline, weeks 4 and 8. Seventy-two patients were included in the trial. At the end of the dietary phase, both diet groups significantly reduced their BP, but there were no between-group differences. Compared to placebo, at the end of follow-up, subjects in the allopurinol group had a lower clinic systolic blood pressure and this was significant within- and between-group comparisons. The percentage of dippers was higher in the allopurinol group, and weight was reduced significantly despite the absence of caloric restriction Allopurinol was associated with a significant reduction in clinic BP, an increase in the percentage of dippers, and significant weight loss. Larger studies with longer follow-up are needed to confirm our findings. Copyright © 2015 American Society of Hypertension. All rights reserved.

  2. Antihypertensive Potential of Combined Extracts of Olive Leaf, Green Coffee Bean and Beetroot: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial

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    Rachel H.X. Wong

    2014-11-01

    Full Text Available Extracts of olive leaf, green coffee bean and beetroot may deliver cardiovascular benefits. This study sought to evaluate the effects of regularly consuming a combination of these extracts on blood pressure (BP, arterial compliance, blood lipids, blood glucose and insulin sensitivity. A double-blind randomised placebo-controlled crossover trial was conducted in adults with untreated high normal or borderline elevated BP. They were randomised to take an active supplement, comprising 500 mg olive leaf extract, 100 mg green coffee bean extract and 150 mg beet powder, or a matching placebo twice daily for six weeks, followed by the alternate supplement for a further six weeks. Assessments of 24-h ambulatory BP (ABP, clinic BP arterial compliance (pulse-wave analysis, blood lipids, blood glucose and insulin were obtained at baseline and at the end of each treatment phase. Baseline clinic BP in 37 overweight middle-aged men and women who completed the trial averaged 145/84 mmHg. There was no significant effect of treatment on ABP or any other outcome measure. The failure to confirm prior evidence of the antihypertensive benefits of these extracts emphasises the importance of placebo control and the value of ABP monitoring. Further dose-response evaluation of olive leaf, green coffee bean or beetroot extracts is required to confirm or refute the purported benefits.

  3. Antihypertensive potential of combined extracts of olive leaf, green coffee bean and beetroot: a randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    Wong, Rachel H X; Garg, Manohar L; Wood, Lisa G; Howe, Peter R C

    2014-11-05

    Extracts of olive leaf, green coffee bean and beetroot may deliver cardiovascular benefits. This study sought to evaluate the effects of regularly consuming a combination of these extracts on blood pressure (BP), arterial compliance, blood lipids, blood glucose and insulin sensitivity. A double-blind randomised placebo-controlled crossover trial was conducted in adults with untreated high normal or borderline elevated BP. They were randomised to take an active supplement, comprising 500 mg olive leaf extract, 100 mg green coffee bean extract and 150 mg beet powder, or a matching placebo twice daily for six weeks, followed by the alternate supplement for a further six weeks. Assessments of 24-h ambulatory BP (ABP), clinic BP arterial compliance (pulse-wave analysis), blood lipids, blood glucose and insulin were obtained at baseline and at the end of each treatment phase. Baseline clinic BP in 37 overweight middle-aged men and women who completed the trial averaged 145/84 mmHg. There was no significant effect of treatment on ABP or any other outcome measure. The failure to confirm prior evidence of the antihypertensive benefits of these extracts emphasises the importance of placebo control and the value of ABP monitoring. Further dose-response evaluation of olive leaf, green coffee bean or beetroot extracts is required to confirm or refute the purported benefits.

  4. 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

  5. Randomized placebo-controlled D-cycloserine with cognitive behavior therapy for pediatric posttraumatic stress.

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    Scheeringa, Michael S; Weems, Carl F

    2014-03-01

    Abstract Objective: Research on D-cycloserine (DCS), a partial N-methyl-d-aspartic acid (NMDA) agonist, has suggested that it may enhance exposure-based therapies for anxiety disorders. RESULTS with DCS in adult posttraumatic stress disorder (PTSD) have been conflicting; however, no data have been reported on children with PTSD. Although many individuals with PTSD respond to exposure-based cognitive behavioral therapy (CBT), there are subgroups of individuals who are nonresponders, and many responders still have substantial residual symptoms. This randomized, triple-blind, placebo-controlled study tested DCS as an adjunct to CBT to improve and speed treatment response for PTSD in youth. Seven to 18 year-old youth with exposure to trauma and PTSD were offered a 12 session, manualized CBT treatment. Those who remained in treatment at the fifth session were randomly allocated (n=57) to either CBT and DCS or CBT and placebo. Youth in the CBT and DCS group had significant reductions in symptoms, but these reductions were not greater than those in the CBT and placebo group. There was a trend toward DCS speeding PTSD symptom recovery during the exposure-based sessions, and evidence that the CBT and DCS group better maintained stability of gains on inattention ratings from posttreatment to the 3 month follow-up. This initial study of CBT and DCS to treat pediatric PTSD provided suggestive and preliminary evidence for more rapid symptom recovery and beneficial effects on attention, but did not show an overall greater effect for reducing PTSD symptoms. It appears that augmentation with DCS represents unique challenges in PTSD. Because PTSD involves complex, life-threatening trauma memories, as opposed to the imagined dreadful outcomes of other anxiety disorders, the use of DCS may require greater attention to how its use is coupled with exposure-based techniques. DCS may have inadvertently enhanced reconsolidation of trauma memories rather than more positive and adaptive

  6. 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.

  7. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial.

    Science.gov (United States)

    Blauvelt, Andrew; Papp, Kim A; Griffiths, Christopher E M; Randazzo, Bruce; Wasfi, Yasmine; Shen, Yaung-Kaung; Li, Shu; Kimball, Alexa B

    2017-03-01

    Guselkumab, an interleukin-23 blocker, was superior to adalimumab in treating moderate to severe psoriasis in a phase II trial. We sought to compare efficacy and safety of guselkumab with adalimumab and placebo in patients with psoriasis treated for 1 year. Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 329); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20, then every 8 weeks; n = 174); or adalimumab (80 mg week 0, 40 mg week 1, then 40 mg every 2 weeks through week 47; n = 334). Physician-reported outcomes (Investigator Global Assessment, Psoriasis Area and Severity Index [PASI]), patient-reported outcomes (Dermatology Life Quality Index, Psoriasis Symptoms and Signs Diary), and safety were evaluated through week 48. Guselkumab was superior (P < .001) to placebo at week 16 (85.1% vs 6.9% [Investigator Global Assessment score of 0/1 (cleared/minimal)] and 73.3% vs 2.9% [90% or greater improvement in PASI score from baseline (PASI 90)]). Guselkumab was also superior (P < .001) to adalimumab for Investigator Global Assessment 0/1 and PASI 90 at week 16 (85.1% vs 65.9% and 73.3% vs 49.7%), week 24 (84.2% vs 61.7% and 80.2% vs 53.0%), and week 48 (80.5% vs 55.4% and 76.3% vs 47.9%). Furthermore, guselkumab significantly improved patient-reported outcomes through week 48. Adverse event rates were comparable between treatments. Analyses were limited to 48 weeks. Guselkumab demonstrated superior efficacy compared with adalimumab and was well tolerated in patients with psoriasis through 1 year. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. To evaluate efficacy and safety of Caralluma fimbriata in overweight and obese patients: A randomized, single blinded, placebo control trial

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    Ekta Arora

    2015-01-01

    Full Text Available Aim: The aim of the following study is to evaluate the efficacy and safety of Caralluma fimbriata extract (CFE in overweight and obese individuals in a prospective, randomized, placebo controlled trial. Materials and Methods: Commercially available CFE was assessed in overweight and obese individuals. A total of 89 patients were randomized into a treatment group (n = 47 and placebo group (n = 42 to receive either CFE in the form capsules/oral 500 mg b.d. for 12 weeks or matching placebo in similar way. Patients were evaluated clinically and biochemically at 4, 8 and 12 weeks for anthropometric measurements, appetite, biochemical investigations and other safety parameters. Results: At the end of study period both CFE and placebo for 12 weeks caused only numerical reduction in weight, body mass index, waist circumference, hip circumference and waist hip ratio in overweight and obese individuals. However, these parameters failed to attain significant statistical levels (P ≥ 0.05. CFE and placebo both failed to elucidate any modification of the appetite. There were no significant changes in the biochemical and clinical parameters in both the test and placebo group. However, CFE was well-tolerated and adverse events noted were mild and transient in nature. Conclusion: A commercially available extract of CFE in an oral dose of 1 g/day claimed to have anti-obesity effect failed to yield any positive results on anthropometry and appetite in overweight and obese individuals beyond placebo. There were also no significant differences in the clinical and biochemical parameters. However, CFE was well tolerated. Thereby, underscoring the need to carry more research before CFE is recommended as an anti-obesity drug.

  9. Safety and effectiveness of autoinoculation therapy in cutaneous warts: A double - blind, randomized, placebo - controlled study

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    Niharika Ranjan Lal

    2014-01-01

    Full Text Available Background: In spite of the availability of multiple treatment options, viral warts are known for their persistence and recurrence, causing frustration to patients and treating physicians. Aims: To study the effectiveness and safety of autoinoculation as a treatment modality in cutaneous warts. Methods: A double-blind, placebo-controlled study was carried out. In the treatment group, full-thickness warty tissue was excised, minced and implanted in a small dermal pocket. In the control group, warty tissue was only excised and not implanted, though a dermal pocket was made. Patients were evaluated every four weeks with lesion counts. The procedure was repeated at 4 and 8 weeks. Response was assessed at each visit and at 12 weeks. Results: Forty-eight patients with cutaneous warts (male: female = 32:16 were randomized into autoinoculation and control groups. The number of warts at baseline was comparable in both groups (P = 0.293. Reduction in the number of warts was significantly more in the autoinoculation group (8.50 ± 13.88 than in the control group (10.04 ± 5.80 from 8 weeks onwards (P = 0.010. Complete resolution occurred only in the autoinoculation group, in 62.5% of cases. Adverse effects were seen in 11 patients, including infection of the donor site (5 cases, keloid formation (3 and hypopigmentation (3. Conclusion: Autoinoculation may be an effective therapeutic modality for cutaneous warts and two sessions may be required for optimum results.

  10. Oxycodone and dexamethasone for pain management after tonsillectomy: a placebo-controlled EMG assessed clinical trial.

    Science.gov (United States)

    Vaiman, Michael; Krakovski, Daniel; Haitov, Zoe

    2011-10-01

    Surface electromyographic (sEMG) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy. 90 randomly chosen operated adults were divided into three groups. Group 1 (n = 30) was treated with OxyContin (Oxycodone) injections; Group 2 (n = 30) was treated with Dexacort (Dexamethasone), and Group 3 (n = 30) was a placebo group. Pain assessment included visual analogue scale (VAS) pain score and the EMG data like the timing, electric amplitude and graphic patterns of muscular activity during deglutition. We investigated masseter, infrahyoid and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The patients were tested 24 h after surgery. The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients. Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition. Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records. Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group. Application of oxycodone significantly reduces the postoperative pain. Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema. SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia.

  11. A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions

    OpenAIRE

    de Vos van Steenwijk, Peggy J.; Ramwadhdoebe, Tamara H.; Löwik, Margriet J. G.; van der Minne, Caroline E.; Berends-van der Meer, Dorien M A; Fathers, Lorraine M; Valentijn, A. Rob P. M.; Oostendorp, Jaap; Fleuren, Gert Jan; Hellebrekers, Bart W. J.; Welters, Marij J. P.; van Poelgeest, Mariette I.; Melief, Cornelis J. M.; Kenter, Gemma G; van der Burg, Sjoerd H.

    2012-01-01

    The aim of this study was to investigate the capacity of an HPV16 E6/E7 synthetic overlapping long-peptide vaccine to stimulate the HPV16-specific T-cell response, to enhance the infiltration of HPV16-specific type 1 T cells into the lesions of patients with HPV16+ high-grade cervical squamous intraepithelial lesion (HSIL) and HPV clearance. This was a placebo-controlled randomized phase II study in patients with HPV16-positive HSIL. HPV16-specific T-cell responses were determined pre- and po...

  12. Smoking cessation or reduction with nicotine replacement therapy: a placebo-controlled double blind trial with nicotine gum and inhaler

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    Gustavsson Gunnar

    2009-11-01

    Full Text Available Abstract Background Even with effective smoking cessation medications, many smokers are unable to abruptly stop using tobacco. This finding has increased interest in smoking reduction as an interim step towards complete cessation. Methods This multi-center, double-blind placebo-controlled study evaluated the efficacy and safety of nicotine 4 mg gum or nicotine 10 mg inhaler in helping smokers (N = 314 to reduce or quit smoking. It included smokers willing to control their smoking, and participants could set individual goals, to reduce or quit. The study was placebo-controlled, randomized in a ratio of 2:1 (Active:Placebo, and subjects could choose inhaler or gum after randomization. Outcome was short-term (from Week 6 to Month 4 and long-term (from Month 6 to Month 12 abstinence or reduction. Abstinence was defined as not a single cigarette smoked and expired CO readings of Results Significantly more smokers managed to quit in the Active group than in the Placebo group. Sustained abstinence rates at 4 months were 42/209 (20.1% subjects in the Active group and 9/105 (8.6% subjects in the Placebo group (p = 0.009. Sustained abstinence rates at 12 months were 39/209 (18.7% and 9/105 (8.6%, respectively (p = 0.019. Smoking reduction did not differ between the groups, either at short-term or long-term. Twelve-month reduction results were 17.2% vs. 18.1%, respectively. No serious adverse events were reported. Conclusion In conclusion, treatment with 10 mg nicotine inhaler or 4 mg nicotine chewing gum resulted in a significantly higher abstinence rate than placebo. In addition a large number of smokers managed to reduce their cigarette consumption by more than 50% compared to baseline.

  13. A randomized, double-blind, placebo-controlled trial comparing pethidine to metamizol for treatment of post-anaesthetic shivering

    Science.gov (United States)

    MONSÓ, A.; RIUDEUBAS, J.; BARBAL, F.; LAPORTE, J-R.; ARNAU, J. M.

    1996-01-01

    1Shivering is frequent during the post-anaesthetic recovery period, and there is no clear consensus about the best strategy for its treatment. We tested the efficacy of two commonly used analgesic drugs, pethidine and metamizol. 2A randomized, double-blind, placebo-controlled clinical trial was performed, including 104 adult patients who presented with post-anaesthetic shivering during the recovery from general anaesthesia. They were randomized to receive placebo (n=32), metamizol 25 mg kg−1 (n=37), or pethidine 0.4 mg kg−1 (n=35). The response to treatment was assessed 5, 15 and 45 min after drug administration, and the main outcome variable was complete suppression of shivering. 3The efficacy at 5, 15 and 45 min was as follows: placebo 6%, 16% and 37%; metamizol 13.5%, 32% and 76%, and pethidine 89%, 91% and 89%. With both active drugs the efficacy at all three time intervals was significantly higher than that with placebo (Pmetamizol were statistically significant (Pmetamizol produces a better post-anaesthetic shivering response than placebo, especially 15 and 45 min after drug administration; the efficacy of pethidine was the highest and the response to it appeared more quickly; however, at 45 min it was similar to that observed with metamizol. 5Both metamizol and pethidine suppress postanaesthetic shivering, but the latter induces a quicker and more reliable response. PMID:8877020

  14. Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tang, Yu-Ping; Li, Peng-Gao; Kondo, Miwako; Ji, Hong-Ping; Kou, Yan; Ou, Boxin

    2009-08-01

    The effect of a mangosteen product containing multivitamins and essential minerals was tested on immune function and well-being in healthy adults. A randomized, double blinded, placebo-controlled study was conducted in 59 healthy human subjects (40-60 years old). Changes from baseline immune function were measured after a 30-day consumption of the mangosteen product and the placebo. The subjects' self-appraisal of their health status was also surveyed. A xanthone-rich mangosteen product intake increased mean values for peripheral T-helper cell frequency (P = .020) and reduced the serum C-reactive protein concentration (P = .014). Increases in peripheral CD4/CD8 double-positive (DP) T-cell frequency and serum complement C3, C4, and interleukin (IL)-1alpha concentrations were significantly higher in the experimental group than in the placebo group (DP, P = .038; C3, P = .017; C4, P = .031; IL-1alpha, P = .006). At the end of study, serum IL-1alpha and IL-1beta concentrations in the study group were significantly higher than that in the placebo group (IL-1alpha, P = .033; IL-1beta, P = .04). Furthermore, more participants in the experimental group reported greatly improved overall health status compared with participants receiving placebo (P = .001). The results indicated that the intake of an antioxidant-rich product significantly enhanced immune responses and improved the subject's self-appraisal on his or her overall health status.

  15. Efficacy of a CO2-releasing suppository in dyschezia: a double-blind, randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Tarrerias, Anne Laure; Abramowitz, Laurent; Marty, Marc M L; Coulom, Pierre; Staumont, Ghislain; Merlette, Christophe; Berger, Véronique; Savarieau, Bernard; Ducrotté, Philippe

    2014-08-01

    Constipation has a significant impact on quality of life. Aim of this study was to evaluate the safety and the efficacy for relieving dyschezia symptoms of a CO2-releasing suppository in a randomized, placebo-controlled, clinical trial. Fifty-three office-based primary care physicians and 24 gastroenterologists conducted the study in France, between November 2010 and January 2012. Patients (aged 18-75 years) with dyschezia were eligible. Patients were randomly allocated a once-a-day suppository (CO2-releasing suppository or placebo) for 21 days. Primary endpoint was the change, from Day 0 to Day 21, in the intensity of discomfort related to dyschezia based on a self-assessed 0-100 visual analogue scale. A total of 323 patients were randomized, i.e. 166 into the intervention group and 157 into the placebo group. Co-variance analysis showed a greater reduction in discomfort visual analogue scale score in the intervention group (-34.5mm; standard error of the mean: 1.8mm) than in the placebo group (-26.2mm; standard error of the mean: 1.9 mm; psuppository was confirmed for all secondary efficacy parameters. No significant side effects for either treatment were observed. A CO2-releasing suppository is more effective than a placebo for the relief of symptoms of dyschezia. This efficacy is associated with a good safety profile. Copyright © 2014 Editrice Gastro