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Sample records for randomized placebo-controlled double-blinded

  1. Zonisamide for Bipolar Depression: A Randomized, Double Blind, Placebo-Controlled, Adjunctive Trial

    PubMed Central

    Dauphinais, Deborah; Knable, Michael; Rosenthal, Joshua; Polanski, Mark; Rosenthal, Norman

    2011-01-01

    Objective This is the first multicenter, double blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of adjunctive zonisamide for the treatment of bipolar depression. Experimental design One hundred two patients with bipolar disorder, type I or II in the depressed phase of illness were randomized to either adjunctive zonisamide or placebo. The study consisted of three phases, a 7 to 30 day screening and stabilization phase, 6 weeks of blinded treatment and a 1 to 3 week discontinuation phase. MADRS score was the primary outcome variable. Secondary outcome measures included the YMRS, CGI-S, CGI-I, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and an a priori analysis of response and remission. Metabolic parameters including weight, waist-hip ratio, body mass index, fasting glucose, cholesterol and triglyceride levels were also evaluated. Side effects were measured using the SAFTEE. Principal observations There were no statistically significant differences in response between subjects treated with adjunctive zonisamide vs. placebo controls for the primary or secondary outcome measures. There were also no differences between the groups with regard to response rate or remission rate. Conclusions In contrast to preliminary open label studies that suggested a role for zonisamide in bipolar depression, we could not confirm these results in a large double blind controlled study.

  2. Intrathecal Baclofen in Children with Spastic Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study

    ERIC Educational Resources Information Center

    Hoving, Marjanke A.; van Raak, Elisabeth P. M.; Spincemaille, Geert H. J. J.; Palmans, Liesbeth J.; Sleypen, Frans A. M.; Vles, Johan S. H.

    2007-01-01

    Intrathecal baclofen (ITB) therapy can be very effective in the treatment of intractable spasticity, but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy (CP). The aims of this double-blind, randomized, placebo-controlled, dose-finding study were to select children eligible for continuous ITB…

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

    PubMed

    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.

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

    PubMed

    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 < 0.05), group P being intermediate (45 +/- 34 ml/min/1.73 m2). Similarly, effective renal blood flow (ERBF) at 3 months was higher in group NL than in groups P and NS (mean +/- SD 351 +/- 175 versus 216 +/- 166 and 220 +/- 162 ml/min/1.73 m2; P < 0.05). The differences were not significant by 6 months post-transplantation. This study suggests that oral 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.

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

    PubMed Central

    2014-01-01

    Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test. Results Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups. Conclusions Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted. PMID:24773615

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

    PubMed Central

    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

  7. DOUBLE-BLIND, RANDOMIZED PLACEBO-CONTROLLED CLINICAL TRIAL OF BENFOTIAMINE FOR SEVERE ALCOHOL DEPENDENCE

    PubMed Central

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

    2013-01-01

    Background Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analogue, benfotiamine (BF), and BF’s effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. Methods A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Results Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, −611±380 Std Dev; PL: N=11, −159±562 Std Dev, p-value=0.02). Conclusions BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism. PMID:23992649

  8. Pulsed electromagnetic fields in knee osteoarthritis: a double blind, placebo-controlled, randomized clinical trial

    PubMed Central

    Miceli, Giovanni; Marino, Natale; Sciortino, Davide; Bagnato, Gian Filippo

    2016-01-01

    Objectives. This trial aimed to test the effectiveness of a wearable pulsed electromagnetic fields (PEMF) device in the management of pain in knee OA patients. Methods. In this randomized [with equal randomization (1:1)], double-blind, placebo-controlled clinical trial, patients with radiographic evidence of knee OA and persistent pain higher than 40 mm on the visual analog scale (VAS) were recruited. The trial consisted of 12 h daily treatment for 1 month in 60 knee OA patients. The primary outcome measure was the reduction in pain intensity, assessed through VAS and WOMAC scores. Secondary outcomes included quality of life assessment through the 36-item Medical Outcomes Study Short-Form version 2 (SF-36 v2), pressure pain threshold (PPT) and changes in intake of NSAIDs/analgesics. Results. Sixty-six patients were included, and 60 completed the study. After 1 month, PEMF induced a significant reduction in VAS pain and WOMAC scores compared with placebo. Additionally, pain tolerance, as expressed by PPT changes, and physical health improved in PEMF-treated patients. A mean treatment effect of −0.73 (95% CI − 1.24 to − 0.19) was seen in VAS score, while the effect size was −0.34 (95% CI − 0.85 to 0.17) for WOMAC score. Twenty-six per cent of patients in the PEMF group stopped NSAID/analgesic therapy. No adverse events were detected. Conclusion. These results suggest that PEMF therapy is effective for pain management in knee OA patients and also affects pain threshold and physical functioning. Future larger studies, including head-to-head studies comparing PEMF therapy with standard pharmacological approaches in OA, are warranted. Trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01877278 PMID:26705327

  9. Red yeast rice lowers cholesterol in physicians - a double blind, placebo controlled randomized trial

    PubMed Central

    2013-01-01

    Background In recent years, red yeast rice (RYR) supplements have been marketed aggressively as a natural way to lower cholesterol; however, the large majority of commercially available products have not been studied according to current research standards. Methods In a double blind placebo controlled randomized trial, 52 physicians and their spouses with a total cholesterol level of > 200 mg/dL were randomly allocated to receive a RYR extract or placebo for 8 weeks. As a primary outcome measure, we compared the before-after difference in lipid levels between both groups. As secondary outcome measures we looked at side-effects, CK elevation and a change in cardiovascular risk. Results LDL (low density lipoprotein) cholesterol was lowered with 36 mg/dL (22%) and total cholesterol with 37 mg/dL (15%) in the intervention group. This result was statistically significant as compared to the control group, in which no reduction in total cholesterol and LDL was observed (p < 0.001). There was no marked difference in CK (creatine kinase)-elevation or reported side-effects between study groups. In 5/31 participants in the intervention group, the lipid lowering effect resulted in lower cardiovascular risk as measured with SCORE (Systematic COronary Risk Evaluation). Conclusions The RYR formulation under study was effective in lowering cholesterol and LDL cholesterol in this study population. RYR therapy may be an attractive and relatively well studied alternative in patients who are intolerant for statins or who have objections against pharmacological lipid lowering. However, consumers need to be warned that the actual content of commercially available preparations is not assured by governmental regulations, which raises effectiveness and safety issues. Trial registration Clinicaltrials.gov, nr: NCT01558050 PMID:23866314

  10. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease

    PubMed Central

    Thomas, Ronald G.; Craft, Suzanne; van Dyck, Christopher H.; Mintzer, Jacobo; Reynolds, Brigid A.; Brewer, James B.; Rissman, Robert A.; Raman, Rema; Aisen, Paul S.

    2015-01-01

    Objective: A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes). Methods: Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52. Results: Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo. Conclusions: Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood–brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment. Classification of evidence: This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated. PMID:26362286

  11. Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study

    PubMed Central

    Fukuchi, Yoshinosuke; Tatsumi, Koichiro; Inoue, Hiromasa; Sakata, Yukinori; Shibata, Kai; Miyagishi, Hideaki; Marukawa, Yasuhiro; Ichinose, Masakazu

    2016-01-01

    Background/aim Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. Methods In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate. Results A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study. Conclusion The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation. PMID:27143873

  12. Probiotics for standard triple Helicobacter pylori eradication: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Hauser, Goran; Salkic, Nermin; Vukelic, Karina; JajacKnez, Alenka; Stimac, Davor

    2015-05-01

    The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori.The study was multicenter, prospective, randomized, placebo controlled, and double-blind. The subjects first filled out a specially designed questionnaire to assess the severity of the 10 symptoms, which can be related to eradication therapy to be monitored during the trial. Each subject then received 28 capsules of probiotic preparation or matching placebo capsules, which they were supposed to take over the following 14 days, twice a day, at least 2 hours prior to or after the antibiotic therapy administration.A total of 804 patients were enrolled in the trial, of which 650 (80.85%) were included in the analysis. The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm (87.38% vs 72.55%; P < 0.001). Additionally, presence and intensity of epigastric pain, bloating, flatulence, taste disturbance, loss of appetite, nausea, vomiting, heartburn, rash, and diarrhea were monitored over the study period. At 15 days postinclusion, probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms. Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group, 0.76 vs 0.55 (P < 0.001).Adding probiotics to the standard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease.

  13. Randomized, double-blind, placebo-controlled study of transdermal nicotine patch for smoking cessation.

    PubMed

    Perng, R P; Hsieh, W C; Chen, Y M; Lu, C C; Chiang, S J

    1998-08-01

    Smoking cessation is an arduous process because nicotine withdrawal syndrome, which occurs following sudden interruption of nicotine use in long-term smokers, frequently prevents them from giving up the habit. Nicotine supplement systems may relieve smokers' nicotine withdrawal symptoms and, thus, help in the process of abstinence from smoking. The purpose of the present study was to investigate the effectiveness and safety of a 30-mg transdermal nicotine patch in a smoking cessation program for Chinese smokers. In this randomized, double-blind, placebo-controlled study, 30 heavy smokers, who had smoked more than 20 cigarettes per day for more than a year, were treated with 30-mg transdermal nicotine patches, and 32 heavy smokers were given placebo patches during a 6-week smoking cessation program. The clinical characteristics of the two groups were similar. After 6 weeks, the use of the transdermal nicotine patch was associated with markedly reduced nicotine dependence and severity of withdrawal symptoms. Nineteen (63%, 95% confidence interval, CI, 46%-80%) of the smokers treated with the transdermal nicotine patch had successfully quit smoking at the end of the program (6 weeks) and nine (30%, 95% CI 14%-46%) remained abstinent 1 year later. In contrast, only 11 (34%, 95% CI 18%-50%) of the smokers in the placebo group had successfully stopped smoking after 6 weeks, and three remained abstinent 1 year later (9%, 95% CI 0%-19%). However, there was no statistically significant difference between the two groups of smokers after 1 year of follow-up (p = 0.08). Side-effects were minimal and did not affect the efficacy of the skin patch. The results indicate that the transdermal nicotine patch is an effective aid in smoking cessation programs.

  14. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial.

    PubMed

    Panahi, Yunes; Rahimnia, Ali-Reza; Sharafi, Mojtaba; Alishiri, Gholamhossein; Saburi, Amin; Sahebkar, Amirhossein

    2014-11-01

    Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long-term adverse events of currently available medications including non-steroidal anti-inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti-inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double-blind placebo-control parallel-group clinical trial was conducted among patients with mild-to-moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p < 0.001) and LPFI (p = 0.013) scores compared with placebo. With respect to WOMAC subscales, there were significant improvements in the pain and physical function scores (p < 0.001) but not stiffness score (p > 0.05). There was no considerable adverse effect in both groups. To conclude, curcuminoids represent an effective and safe alternative treatment for OA. PMID:24853120

  15. Vaccine for Cocaine Dependence: A Randomized Double-Blind Placebo-Controlled Efficacy Trial

    PubMed Central

    Kosten, Thomas R.; Domingo, Coreen B.; Shorter, Daryl; Orson, Frank; Green, Charles; Somoza, Eugene; Sekerka, Rachelle; Levin, Frances R.; Mariani, John J.; Stitzer, Maxine; Tompkins, D. Andrew; Rotrosen, John; Thakkar, Vatsal; Smoak, Benjamin; Kampman, Kyle

    2014-01-01

    Aims We evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence. Methods This 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome. Results The 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of ≥ 42 μg/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths. Conclusions The vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence. PMID:24793366

  16. Immunomodulatory Effects of ResistAid™: A Randomized, Double-Blind, Placebo-Controlled, Multidose Study

    PubMed Central

    Udani, Jay K.

    2013-01-01

    Objective To evaluate the ability of a proprietary arabinogalactan extract from the larch tree (ResistAid, Lonza Ltd., Basel, Switzerland) to change the immune response in healthy adults to a standardized antigenic challenge (tetanus and influenza vaccines) in a dose-dependent manner compared to placebo. Methods This randomized, double-blind, placebo-controlled trial included 75 healthy adults (18–61 years old). Subjects were randomized to receive either 1.5 or 4.5 g/day of ResistAid or placebo for 60 days. At day 30, subjects were administered both tetanus and influenza vaccines. Serum antigenic response (tetanus immunoglobulin G [IgG], influenza A and B IgG and immunoglobulin M [IgM]) was measured at days 45 (15 days after vaccination) and 60 (30 days after vaccination) of the study and compared to baseline antibody levels. Frequency and intensity of adverse events were monitored throughout the study. Results As expected, all 3 groups demonstrated an expected rise in tetanus IgG levels 15 and 30 days following the vaccine. There was a strongly significant difference in the rise in IgG levels at day 60 in the 1.5 g/day group compared to placebo (p = 0.008). In the 4.5 g/day group, there was significant rise in tetanus IgG at days 45 and 60 compared to baseline (p < 0.01) but these values were not significant compared to placebo. Neither group demonstrated any significant elevations in IgM or IgG antibodies compared to placebo following the influenza vaccine. There were no clinically or statistically significant or serious adverse events. Conclusions ResistAid at a dose of 1.5 g/day significantly increased the IgG antibody response to tetanus vaccine compared to placebo. In conjunction with earlier studies, this validates the effect of ResistAid on the augmentation of the response to bacterial antigens (in the form of vaccine). PMID:24219376

  17. Hypercaloric enteral nutrition in Amyotrophic Lateral Sclerosis: a randomized double-blind placebo-controlled trial

    PubMed Central

    Wills, Anne-Marie; Hubbard, Jane; Macklin, Eric A.; Glass, Jonathan; Tandan, Rup; Simpson, Ericka P; Brooks, Benjamin; Gelinas, Deborah; Mitsumoto, Hiroshi; Mozaffar, Tahseen; Hanes, Gregory P.; Ladha, Shafeeq S.; Heiman-Patterson, Terry; Katz, Jonathan; Lou, Jau-Shin; Mahoney, Katy; Grasso, Daniela; Lawson, Robert; Yu, Hong; Cudkowicz, Merit

    2014-01-01

    Background Amyotrophic Lateral Sclerosis (ALS) is a rapidly fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in ALS patients and calorie-dense diets increase survival in an ALS mouse model. We therefore hypothesized that hypercaloric diets might lead to weight gain and slow ALS disease progression. Methods In this double-blind, placebo-controlled, multi-center clinical trial, we enrolled adults with ALS without a history of diabetes, significant liver or cardiovascular disease, who were already receiving percutaneous enteral nutrition. We randomly assigned participants to one of three dietary interventions: replacement calories using an isocaloric diet (controls) vs. a high-carbohydrate hypercaloric diet (HC/HC), vs. a high-fat hypercaloric diet (HF/HC). Participants received the intervention diets for four months and were followed for five months. The primary outcomes were safety and tolerability. Secondary outcomes included measures of disease progression, survival, and metabolism. This trial is registered with Clinicaltrials.gov, number NCT00983983. Findings A total of 24 participants were enrolled of whom 20 initiated study diet (six control, eight HC/HC, six HF/HC). Baseline demographics were similar among the three study arms. The HC/HC diet was better tolerated with fewer serious adverse events than the control diet (zero vs. nine, p<0·001) and fewer dose discontinuations due to adverse events (0% vs. 50%). There were no deaths in the HC/HC arm vs. three deaths (43%) in the control arm (logrank p = 0·03). The HF/HC arm was not statistically different from the controls in adverse events, tolerability, deaths or disease progression. Interpretation Our results suggest that hypercaloric enteral nutrition is safe and tolerable in ALS and support the study of nutritional interventions at earlier stages of the disease. Funding The Muscular Dystrophy Association with additional support from the National

  18. The effectiveness of intramuscular biperiden in acute akathisia: a double-blind, randomized, placebo-controlled study.

    PubMed

    Baskak, Bora; Atbasoglu, E Cem; Ozguven, Halise Devrimci; Saka, Meram Can; Gogus, Ali Kemal

    2007-06-01

    Neuroleptic-induced acute akathisia (NIA) is a distressing condition and an important clinical problem because it is associated with treatment noncompliance and suicidal or impulsive behavior. Anticholinergics are among the treatment options; however, a review of the literature fails to identify a double-blind, randomized, placebo-controlled study of these medications in NIA. In a randomized, double-blind, placebo-controlled design, we studied the effectiveness of intramuscular biperiden (n = 15) or isotonic saline (n = 15) in the treatment of NIA diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Injections were repeated up to 3 times unless akathisia was completely treated (scored 0 for global akathisia with the Barnes Akathisia Rating Scale). Patients were assessed for akathisia, other movement disorders, and psychiatric symptoms at baseline and 3 times after the first injection at 2-hour intervals. Response was defined as at least a 2-point decline in the global akathisia score. The numbers of responders in the 2 groups were not significantly different (7 and 5 in the biperiden and placebo groups, respectively). The courses of individual items on the Barnes Akathisia Rating Scale were also similar. Our results suggest that intramuscular biperiden should not be considered as a first-line treatment of NIA.

  19. Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial

    PubMed Central

    McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

    2002-01-01

    Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information. PMID:11934908

  20. Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial.

    PubMed

    McCarney, R; Fisher, P; Spink, F; Flint, G; van Haselen, R

    2002-04-01

    Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load. A randomized double-blind trial was conducted to determine whether six dowsing homeopaths were able to distinguish between Bryonia in a 12c potency and placebo by use of dowsing alone. The homeopathic medicine Bryonia was correctly identified in 48.1% of bottle pairs (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689). These results, wholly negative, add to doubts whether dowsing in this context can yield objective information. PMID:11934908

  1. Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial.

    PubMed

    Mooney, M E; Schmitz, J M; Allen, S; Grabowski, J; Pentel, P; Oliver, A; Hatsukami, D K

    2016-10-01

    Combination of non-nicotine pharmacotherapies has been underexamined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP + NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP + NTX, 54.1%; BUP + PBO, 33.3%), P = 0.0210, but not at 6-month follow-up (BUP + NTX, 27.9%; BUP + PBO, 15.0%), P = 0.09. Continuous abstinence rates did not differ, P = 0.0740 (BUP + NTX, 26.2%; BUP + PBO, 13.3%). Those receiving BUP + NTX reported reduced nicotine withdrawal, P = 0.0364. The BUP + NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups. PMID:27213949

  2. Baclofen for stroke patients with persistent hiccups: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    2014-01-01

    Background The results of preclinical studies suggest that baclofen may be useful in the treatment of stroke patients with persistent hiccups. This study was aimed to assess the possible efficacy of baclofen for the treatment of persistent hiccups after stroke. Methods In total, 30 stroke patients with persistent hiccups were randomly assigned to receive baclofen (n = 15) or a placebo (n = 15) in a double-blind, parallel-group trial. Participants in the baclofen group received 10 mg baclofen 3 times daily for 5 days. Participants assigned to the placebo group received 10 mg placebo 3 times daily for 5 days. The primary outcome measure was cessation of hiccups. Secondary outcome measures included efficacy in the two groups and adverse events. Results All 30 patients completed the study. The number of patients in whom the hiccups completely stopped was higher in the baclofen group than in the placebo group (relative risk, 7.00; 95% confidence interval, 1.91–25.62; P = 0.003). Furthermore, efficacy was higher in the baclofen group than in the placebo group (P < 0.01). No serious adverse events were documented in either group. One case each of mild transient drowsiness and dizziness was present in the baclofen group. Conclusions Baclofen was more effective than a placebo for the treatment of persistent hiccups in stroke patients. Trial registration Chinese Clinical Trials Register: ChiCTR-TRC-13004554 PMID:25052238

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

    PubMed

    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. A randomized, double blind, placebo controlled study of spirulina supplementation on indices of mental and physical fatigue in men.

    PubMed

    Johnson, Morgan; Hassinger, Lauren; Davis, Joshua; Devor, Steven T; DiSilvestro, Robert A

    2016-01-01

    Spirulina may increase people's ability to resist mental and physical fatigue. This study tested that hypothesis in a randomized, double blinded, placebo controlled study in men. After 1 week, a 3 g/day dose of spirulina produced a small, but statistically significant increase in exercise output (Kcals consumed in 30 min exercise on a cross trainer machine). A mathematical based mental fatigue test showed improved performance 4 h after the first time of supplementation as well as 8 weeks later. Similarly, a subjective survey for a sense of physical and mental fatigue showed improvement within 4 h of the first supplementation as well as 8 weeks later. These results show that spirulina intake can affect fatigue in men. PMID:26888417

  5. Zonisamide for Bipolar Disorder, Mania or Mixed States: A Randomized, Double Blind, Placebo-Controlled Adjunctive Trial

    PubMed Central

    Dauphinais, Deborah; Knable, Michael; Rosenthal, Joshua; Polanski, Mark; Rosenthal, Norman

    2011-01-01

    Objective This is the first multicenter, double blind, randomized, placebo-controlled trial to evaluate the safety and efficacy of adjunctive zonisamide for the treatment of bipolar mania or mixed state. Experimental design One hundred four patients with Bipolar Disorder, Type I, II or NOS, in a manic, hypomanic or mixed state of illness were randomized to either adjunctive zonisamide or placebo. The study consisted of three phases: a 7 to 30 day screening and stabilization phase, 6 weeks of blinded treatment and a 1 to 3 week discontinuation phase. The primary outcome variable for manic and hypomanic patients was the Young Mania Rating Scale (YMRS) both the YMRS and Montgomery Asberg Depression Rating Scale (MADRS) served as primary outcome variables for patients in mixed states. Secondary outcome measures included the Clinical Global Impression for Bipolar Disorder (CGI-BP), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and an a priori analysis of response and remission. Metabolic parameters including weight, waist-hip ratio, body mass index, fasting glucose, cholesterol and triglyceride levels were also analyzed. Side effects were measured using the SAFTEE. Principal observations There were no statistically significant differences for any of the primary or secondary outcome measures between zonisamide and placebo-treated patients. Conclusions In contrast to previous studies that suggested efficacy of adjunctive zonisamide in bipolar mania or mixed state, these results were not confirmed in this double blind controlled study. PMID:22506436

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

    ERIC Educational Resources Information Center

    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 =…

  7. A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis.

    PubMed

    Miller, A E; Morgante, L A; Buchwald, L Y; Nutile, S M; Coyle, P K; Krupp, L B; Doscher, C A; Lublin, F D; Knobler, R L; Trantas, F; Kelley, L; Smith, C R; La Rocca, N; Lopez, S

    1997-02-01

    We determined the effect of influenza vaccine in patients with relapsing/remitting MS. Considerable controversy surrounds the question of whether to administer influenza vaccines to MS patients. Prevention of a febrile viral illness is clearly desirable in MS, and previous studies suggest that immunization is safe. Despite this, many clinicians avoid vaccination because they fear precipitating an MS exacerbation. We conducted a multicenter, prospective, randomized, double-blind trial of influenza immunization in patients with relapsing/remitting MS. In the autumn of 1993, 104 patients at five MS centers received either standard influenza vaccine or placebo. Patients were followed for 6 months for evaluation of neurologic status and the occurrence of influenza. Influenza was operationally defined as fever > or = 38 degrees C in the presence of coryza, cough, or sore throat at a time when the disease was present in the community. Attacks were defined in the standard manner, requiring objective change in the examination. Patients were examined at 4 weeks and 6 months after inoculation and were contacted by telephone at 1 week and 3 months. They were also examined at times of possible attacks but not when they were sick with flu-like illness. Three vaccine patients and two placebo patients experienced attacks within 28 days of vaccine (no significant difference). Exacerbation rates in the first month for both groups were equal to or less than expected from published series. The two groups showed no difference in attack rate or disease progression over 6 months. Influenza immunization in MS patients is neither associated with an increased exacerbation rate in the postvaccination period nor a change in disease course over the subsequent 6 months.

  8. Davunetide for Progressive Supranuclear Palsy: a multicenter, randomized, double-blind, placebo controlled trial

    PubMed Central

    Boxer, Adam L.; Lang, Anthony E.; Grossman, Murray; Knopman, David S.; Miller, Bruce L.; Schneider, Lon S.; Doody, Rachelle S.; Lees, Andrew; Golbe, Lawrence I.; Williams, David R.; Corvol, Jean-Cristophe; Ludolph, Albert; Burn, David; Lorenzl, Stefan; Litvan, Irene; Roberson, Erik D.; Höglinger, Günter U.; Koestler, Mary; Jack, Clifford R.; Van Deerlin, Viviana; Randolph, Christopher; Lobach, Iryna V.; Heuer, Hilary W.; Gozes, Illana; Parker, Lesley; Whitaker, Steve; Hirman, Joe; Stewart, Alistair J.; Gold, Michael; Morimoto, Bruce H.

    2014-01-01

    Summary Background Davunetide (AL-108, NAP) is an eightamino acid peptide that promotes microtubule stability and decreases tau phosphorylation in pre-clinical studies. Since PSP is tightly linked to tau pathology, davunetide could be an effective treatment for PSP.The goals of this study were to evaluate the efficacy and safety of davunetide in PSP. Methods A phase 2/3 double-blind, parallel group, clinical trial of davunetide 30 mg or placebo (randomized 1:1) administered intranasally twice daily for 52 weeks was conducted at 48centers. Participants met modifiedNNIPPS criteria for possible or probable PSP. Co-primary endpointswere the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England ADL(SEADL) scale at up to 52 weeks. Data from all individuals who received at least one dose of medication and had a post-baseline efficacy assessment were compared using a rank-based method.Secondary outcomes included the Clinical Global Impression of Change (CGIC) and the change in regional brain volumeon MRI. Clinicaltrials.gov identifier: NCT01110720. Findings 360 participants were screened, 313 were randomized and 243 (77.6%) completed the study. There were no group differences in PSPRS (mean difference: 0.49 [95% CI: −1.5, 2.5], p = 0.72) or SEADL (1% [−2, 4%], p = 0.76) change from baseline (CFB) and mean 52 week CFB PSPRS scores were similar between the davunetide (11.3 [9.8,12.8]) and placebo groups (10.9 [9.1, 13.0]). There wereno differences in any of the secondary or exploratory endpoints. There were 11deaths in the davunetide group and tenin the placebo group. There were more nasal adverse events in the davunetide group. Interpretation Davunetide is well tolerated but is not an effective treatment for PSP. Clinical trials of disease modifying therapy are feasible in PSP and should be pursued with other promising tau-directed therapies. Funding Allon Therapeutics PMID:24873720

  9. N-Acetylcysteine in the Treatment of Pediatric Trichotillomania: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial

    ERIC Educational Resources Information Center

    Bloch, Michael H.; Panza, Kaitlyn E.; Grant, Jon E.; Pittenger, Christopher; Leckman, James F.

    2013-01-01

    Objective: To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method: A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary…

  10. A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF ORAL MATRICARIA RECUTITA (CHAMOMILE) EXTRACT THERAPY OF GENERALIZED ANXIETY DISORDER

    PubMed Central

    Amsterdam, Jay D.; Li, Yimei; Soeller, Irene; Rockwell, Kenneth; Mao, Jun James; Shults, Justine

    2013-01-01

    Objective We conducted a randomized, double-blind, placebo-controlled efficacy and tolerability trial of Matricaria recutita (chamomile) extract therapy in patients with mild to moderate Generalized Anxiety Disorder (GAD). We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile. Materials & Methods 61 outpatients with mild to moderate GAD were enrolled and 57 were randomized to either double blind chamomile extract (n=28) or placebo (n=29) therapy for 8 weeks. The study was powered to detect a statistically significant and clinically meaningful group difference in change over time in total Hamilton Anxiety Rating (HAM-A) scores. Secondary outcomes included change in the Beck Anxiety Inventory score, Psychological Well Being score, Clinical Global Impression Severity score, and the proportion of patients with ≥50% reduction in baseline HAM-A score. Results We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy (p=0.047). Although the study was not powered to identify small to moderate differences in secondary outcomes, we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure. One patient in each treatment group discontinued therapy for adverse events. The proportion of patients experiencing 0, 1, 2, or ≥3 adverse events was not significantly different between groups (p=0.417). Conclusion This is the first, controlled clinical trial of chamomile extract for GAD. The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD. Future studies are needed to replicate these observations. PMID:19593179

  11. Pilot Study of the Effects of Lisdexamfetamine on Cocaine Use: A Randomized, Double-Blind, Placebo-Controlled Trial*

    PubMed Central

    Mooney, Marc E.; Herin, David V.; Specker, Sheila; Babb, David; Levin, Frances R.; Grabowski, John

    2015-01-01

    Background Amphetamine analogues have been demonstrated to have some efficacy in reducing use in cocaine dependent individuals. However, these agents also have potential for abuse. Lisdexamfetamine (LDX), a lysine+dextroamphetamine formulation, has been approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) and as a prodrug, has less abuse potential. Objective This pilot study sought to evaluate the safety, tolerability, and efficacy of LDX as a candidate treatment for cocaine dependence. Methods A randomized, double-blind, placebo-controlled parallel group study served to evaluate LDX in 43 cocaine-dependent individuals: (1) Placebo (PBO; 0 mg, n = 21), (2) LDX (70 mg, n = 22). Participants received medication for 14 weeks. Cocaine use was determined based on urine analysis for benzoylecgonine (BE; a cocaine metabolite). Results Retention rates were higher though not significantly different in the PBO (71.4%) than the LDX condition (57.1%). Compared to those in the PBO condition, those receiving LDX were more likely to report experiencing (ps < .05) diarrhea (45.5% vs. 14.3%), headaches (45.5% vs. 9.5%), and anxiety (31.8% vs. 4.8%). No differences in medication conditions were observed for blood pressure, heart rate, or body weight. In the randomized sample, no differences in cocaine use were seen. Those receiving LDX reported significantly less craving for cocaine than participants receiving PBO. Conclusions LDX did not significantly reduce cocaine use compared to PBO in the randomized sample. PMID:26116930

  12. Antidepressant Augmentation Using the NMDA-Antagonist Memantine: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Smith, Eric G.; Deligiannidis, Kristina M.; Ulbricht, Christine M.; Landolin, Chelsea S.; Patel, Jayendra K.; Rothschild, Anthony J.

    2014-01-01

    Objective Intravenous NMDA antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo-controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial (NCT00344682) of the NMDA antagonist memantine as an augmentation treatment for patients with DSM-IV major depressive disorder. Method 31 participants with partial or nonresponse to their current antidepressant were randomized (from 2006–2011) to add memantine (flexible dose 5–20 mg/day, with all memantine group participants reaching the dose of 20 mg/day) (n= 15) or placebo (n= 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated measures mixed effects models using last-observation-carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects. Results Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (β=0.133, favoring placebo, p=0.74) or at study completion (week 8 MADRS score change: −7.13 +/−6.61 (memantine); −7.25 +/−11.14 (placebo), p=0.97). A minimal-to-small effect size (comparing change to baseline variability) was observed (d=0.19), favoring placebo. Similarly, no substantial effect sizes favoring memantine, nor statistically significant between-group differences, were observed on secondary efficacy or safety outcomes. Conclusions This trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment against

  13. Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial.

    PubMed

    Ghaleiha, Ali; Ghyasvand, Mohammad; Mohammadi, Mohammad-Reza; Farokhnia, Mehdi; Yadegari, Noorollah; Tabrizi, Mina; Hajiaghaee, Reza; Yekehtaz, Habibeh; Akhondzadeh, Shahin

    2014-07-01

    The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms.

  14. Salivary antioxidants of male athletes after aerobic exercise and garlic supplementation on: A randomized, double blind, placebo-controlled study

    PubMed Central

    Damirchi, Arsalan; Saati Zareei, Alireza; Sariri, Reyhaneh

    2015-01-01

    Purpose Production of reactive oxygen species and reactive nitrogen species is a natural biological event in metabolism. However, the presence of antioxidants can highly reduce the negative effect of free radicals. Thus, the efficiency of antioxidant system in the physiology of exercise is very important. Design Considering the known antioxidant capacity of garlic, the purpose of this study was to evaluate the effect on combining 14 days aerobic exercise till exhaustion with garlic extract supplementation on the antioxidant capacity of saliva. Methods Sixteen young men volunteered to participate in this randomized, double blind, placebo-controlled study and were randomly placed into two groups, placebo (Group I) and garlic extract (Group II). The participants performed exhaustive aerobic exercise on a treadmill before and after supplementation. Their unstimulated salivary samples were collected before, immediately after, and 1 h after the activity. The antioxidant activity in terms of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) was then measured in the collected samples using their specific substrates. Results A significant increase in salivary antioxidant activity of SOD, POD, and CAT was observed in saliva of the supplement group compared to the placebo group (P ≤ 0.05). Conclusion The findings from this study suggest that increased activity of antioxidant enzymes could possibly decrease exercise-induced oxidative damage in male athletes. PMID:26605139

  15. Efficacy of betamethasone valerate medicated plaster on painful chronic elbow tendinopathy: a double-blind, randomized, placebo-controlled trial

    PubMed Central

    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

    Summary Objective to investigate the efficacy and safety of a medicated plaster containing betamethasone valerate (BMV) 2.25 mg in patients with chronic elbow tendinopathy. Methods 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. Results 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. Conclusions 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. PMID:27331041

  16. Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial.

    PubMed

    Talbot, Nick P; Smith, Thomas G; Privat, Catherine; Nickol, Annabel H; Rivera-Ch, Maria; León-Velarde, Fabiola; Dorrington, Keith L; Robbins, Peter A

    2011-01-01

    Acute mountain sickness (AMS) is a common and disabling condition that occurs in healthy individuals ascending to high altitude. Based on the ability of iron to influence cellular oxygen sensing pathways, we hypothesized that iron supplementation would protect against AMS. To examine this hypothesis, 24 healthy sea-level residents were randomized to receive either intravenous iron(III)-hydroxide sucrose (200 mg) or saline placebo, before ascending rapidly to Cerro de Pasco, Peru (4340 m). The Lake Louise scoring system was used to assess incidence and severity of AMS at sea level and on the first full day at altitude. No significant difference in absolute AMS score was detected between the two groups either at baseline or at high altitude. However, the mean increase in AMS score was 65% smaller in the iron group than in the saline group (p<0.05), and the change in AMS score correlated negatively with the change in ferritin (R=-0.43; p<0.05). Hematocrit and arterial oxygen saturation were unaffected by iron. In conclusion, this preliminary randomized, double-blinded, placebo-controlled trial suggests that intravenous iron supplementation may protect against the symptoms of AMS in healthy volunteers.

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

    PubMed Central

    Kim, Kyung-Ah; Yim, Jung-Eun

    2015-01-01

    Background: Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman. Methods: This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively. Results: Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption. Conclusions: These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women. PMID:26473159

  18. Oral zinc sulphate supplementation for six months in SCA2 patients: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Velázquez-Pérez, Luis; Rodríguez-Chanfrau, Jorge; García-Rodríguez, Julio Cesar; Sánchez-Cruz, Gilberto; Aguilera-Rodríguez, Raúl; Rodríguez-Labrada, Roberto; Rodríguez-Díaz, Julio Cesar; Canales-Ochoa, Nalia; Gotay, Dennis Almaguer; Almaguer Mederos, Luis E; Laffita Mesa, José M; Porto-Verdecia, Marlene; Triana, Consuelo González; Pupo, Noemí Rodríguez; Batista, Idania Hidalgo; López-Hernandez, Orestes D; Polanco, Iverlis Díaz; Novas, Arelis Jayme

    2011-10-01

    Cuban patients with Spinocerebellar Ataxia type 2 (SCA2) have reduced concentrations of zinc in serum and cerebrospinal fluid (CSF). To assess the effect and safety of zinc supplementation, 36 Cuban SCA2 patients were randomly assigned to receive daily either 50 mg ZnSO(4) or placebo, together with neurorehabilitation therapy in a randomized, double-blind, placebo-controlled clinical trial during 6 months. Outcome measures included the changes of zinc levels in CSF and serum, ataxia score, oxidative stress and saccadic eye movements. At the end of the study, the Zinc-treated group showed: (i) a significant increase of the Zn levels in the CSF, (ii) mild decrease in the ataxia scale subscores for gait, posture, stance and dysdiadochocinesia (iii) reduction of lipid's oxidative damage, and (iv) reduction of saccadic latency when compared with the placebo group. The treatment was safe and well tolerated by all subjects. This study demonstrated the efficacy and safety of Zn supplementation, combined with neurorehabilitation for SCA2 patients and therefore it may encourage further studies on the clinical effect of zinc supplementation in SCA2 based in the conduction of future clinical trials with higher number of subjects.

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

    PubMed Central

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

    2015-01-01

    Background: Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. Objectives: The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. Patients and Methods: This study was a randomized double-blind placebo-controlled trial. Children aged 4 to 16 years with chronic functional abdominal pain (based on Rome III criteria) were enrolled in the study. They were randomly divided into two groups, one receiving probiotic and the other placebo. Results: Forty children received probiotic and forty others placebo. There were no significant differences in age, weight, sex, location of pain, associated symptoms, frequency and intensity of pain between the groups. The severity and frequency of abdominal pain in the first month compared to baseline was significantly less and at the end of the second month, there was no significant difference between both groups compared to the end of the first month. Conclusions: This study showed that the severity of pain was significantly reduced in both groups. There was no significant difference in pain scores between them. The effect of probiotic and placebo can probably be attributed to psychological effect of the drugs. PMID:26635937

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

    PubMed

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

    2009-08-01

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

  1. Curcumin for Radiation Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Thirty Breast Cancer Patients

    PubMed Central

    Ryan, Julie L.; Heckler, Charles E.; Ling, Marilyn; Katz, Alan; Williams, Jacqueline P.; Pentland, Alice P.; Morrow, Gary R.

    2014-01-01

    Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS =2.6 vs. 3.4; P =0.008). Fisher’s exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P =0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients. PMID:23745991

  2. Oral zinc sulphate supplementation for six months in SCA2 patients: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Velázquez-Pérez, Luis; Rodríguez-Chanfrau, Jorge; García-Rodríguez, Julio Cesar; Sánchez-Cruz, Gilberto; Aguilera-Rodríguez, Raúl; Rodríguez-Labrada, Roberto; Rodríguez-Díaz, Julio Cesar; Canales-Ochoa, Nalia; Gotay, Dennis Almaguer; Almaguer Mederos, Luis E; Laffita Mesa, José M; Porto-Verdecia, Marlene; Triana, Consuelo González; Pupo, Noemí Rodríguez; Batista, Idania Hidalgo; López-Hernandez, Orestes D; Polanco, Iverlis Díaz; Novas, Arelis Jayme

    2011-10-01

    Cuban patients with Spinocerebellar Ataxia type 2 (SCA2) have reduced concentrations of zinc in serum and cerebrospinal fluid (CSF). To assess the effect and safety of zinc supplementation, 36 Cuban SCA2 patients were randomly assigned to receive daily either 50 mg ZnSO(4) or placebo, together with neurorehabilitation therapy in a randomized, double-blind, placebo-controlled clinical trial during 6 months. Outcome measures included the changes of zinc levels in CSF and serum, ataxia score, oxidative stress and saccadic eye movements. At the end of the study, the Zinc-treated group showed: (i) a significant increase of the Zn levels in the CSF, (ii) mild decrease in the ataxia scale subscores for gait, posture, stance and dysdiadochocinesia (iii) reduction of lipid's oxidative damage, and (iv) reduction of saccadic latency when compared with the placebo group. The treatment was safe and well tolerated by all subjects. This study demonstrated the efficacy and safety of Zn supplementation, combined with neurorehabilitation for SCA2 patients and therefore it may encourage further studies on the clinical effect of zinc supplementation in SCA2 based in the conduction of future clinical trials with higher number of subjects. PMID:21562746

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

    PubMed Central

    Shin, Jae-Young; Ku, Boncho; Kim, Jaeuk U.; Lee, Yu Jung; Kang, Jae Hui; Heo, Hyun; Choi, Hyo-Joon; Lee, Jun-Hwan

    2015-01-01

    Purpose. This trial was performed to investigate the efficacy of laser acupuncture for the alleviation of lower back pain. Methods. This was a randomized, placebo-controlled, double-blind trial. Fifty-six participants were randomly assigned to either the laser acupuncture group (n = 28) or the sham laser acupuncture group (n = 28). Participants in both groups received three treatment sessions over the course of one week. Thirteen acupuncture points were selected. The visual analogue scale for pain, pressure pain threshold, Patient Global Impression of Change, and Euro-Quality-of-Life Five Dimensions questionnaire (Korean version) were used to evaluate the effect of laser acupuncture treatment on lower back pain. Results. There were no significant differences in any outcome between the two groups, although the participants in both groups showed a significant improvement in each assessed parameter relative to the baseline values. Conclusion. Although there was no significant difference in outcomes between the two groups, the results suggest that laser acupuncture can provide effective pain alleviation and can be considered an option for relief from lower back pain. Further studies using long-term intervention, a larger sample size, and rigorous methodology are required to clarify the effect of laser acupuncture on lower back pain. PMID:26516333

  4. Evaluation of a Crataegus-Based Multiherb Formula for Dyslipidemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Zeng, Weiwei; Tomlinson, Brian

    2014-01-01

    Background. We for the first time examined the effects of a multiherb formula containing Crataegus pinnatifida (1 g daily), Alisma orientalis, Stigma maydis, Ganoderma lucidum, Polygonum multiflorum, and Morus alba on plasma lipid and glucose levels in Chinese patients with dyslipidemia. Methods. In this randomized, double-blind, placebo-controlled study, 42 patients were randomized at a ratio of 1 : 1 to receive the herbal formula or placebo for 12 weeks and 40 patients completed the study. Lipid profiles, glucose, glycated haemoglobin (HbA1c), and laboratory safety parameters were performed before and after treatment. Results. The difference in the changes in low-density lipoprotein cholesterol (LDL-C) levels between placebo and active treatment (−9%) was significantly (P < 0.05) better with active treatment. HbA1c levels significantly decreased by −3.9% in the active treatment group, but the change was not significantly different from that with placebo (−1.1%) (P = 0.098). There were no apparent adverse effects or changes in laboratory safety parameters with either treatment. Conclusions. The multiherb formula had mild beneficial effects on plasma LDL-C after 12-weeks treatment in subjects with dyslipidemia without any noticeable adverse effects. PMID:24834096

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

    PubMed

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

    2015-01-01

    Vitamin C ascorbic acid) is a well-known antioxidant that is involved in anxiety, stress, depression, fatigue and mood state in humans. Studies have suggested that oxidative stress may trigger neuropsychological disorders. Antioxidants may play an important therapeutic role in combating the damage caused by oxidative stress in individuals that suffer from anxiety. In this context, it was hypothesized that oral vitamin C supplementation would reduce anxiety. However, few up to date studies have evaluated the consequences of oral vitamin C supplementation on anxiety in humans. The present study examined the effects of oral vitamin C supplements in 42 high school students, in a randomized, double-blind, placebo-controlled trial. The students were given either vitamin C (500 mg day(-1)) or placebo. Plasma concentrations of vitamin C and blood pressure were measured before the intervention and then one day after the intervention. Anxiety levels were evaluated for each student before and after 14 days following supplementation with the Beck Anxiety Inventory. Results showed that vitamin C reduced anxiety levels and led to higher plasma vitamin C concentration compared to the placebo. The mean heart rates were also significantly different between vitamin C group and placebo control group. Present study results not only provide evidence that vitamin C plays an important therapeutic role for anxiety but also point a possible use for antioxidants in the prevention or reduction of anxiety. This suggests that a diet rich in vitamin C may be an effective adjunct to medical and psychological treatment of anxiety and improve academic performance. PMID:26353411

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

    PubMed Central

    2011-01-01

    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 PMID:21827704

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

    PubMed

    Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

    2016-01-01

    The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14-65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood. PMID:26870678

  8. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone.

    PubMed

    Waldinger, M D; Zwinderman, A H; Olivier, B

    2001-06-01

    Antidepressant medication is often associated with sexual side effects. A double-blind, placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin (5-HT) reuptake inhibitors--paroxetine and sertraline--and the 5-HT2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate. Forty-eight men with an intravaginal ejaculation latency time (IELT) of a maximum of 1 minute were randomly assigned to receive paroxetine (20 mg/day), sertraline (50 mg/day), nefazodone (400 mg/day), or placebo for 6 weeks. During the 1-month baseline and 6-week treatment period, IELTs were measured at home with a stopwatch. The trial was completed by 40 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was stable at approximately 20 seconds. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.002); the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds, respectively, compared with 28 seconds in the nefazodone group. The paroxetine and sertraline groups differed significantly (p < 0.001 and p = 0.024, respectively) from placebo, but the nefazodone group did not (p = 0.85). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, whereas sertraline delayed it only moderately. There was no clinically relevant delay in ejaculation with nefazodone.

  9. Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial.

    PubMed

    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.

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

    PubMed

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

    2013-05-01

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

  11. Deep mineral water accelerates recovery after dehydrating aerobic exercise: a randomized, double-blind, placebo-controlled crossover study

    PubMed Central

    2014-01-01

    Background The effect of deep mineral water (DMW) with moderate mineralization on the recovery of physical performance after prolonged dehydrating aerobic exercise in the heat was studied in nine healthy, physically active (VO2max = 45.8 ± 8.4 mL kg−1 min−1) women aged 24.0 ± 3.7 years. Methods We conducted a randomized, double-blind, placebo-controlled crossover human study to evaluate the effect of ingestion of natural mineral water extracted from a depth of 689 m on recovery from prolonged fatiguing aerobic running conducted at 30°C. Results Mean body weight decreased by 2.6–2.8% following dehydrating exercise. VO2max was 9% higher after 4 h of recovery after rehydrating with DMW compared with plain water. Leg muscle power recovered better during the slow phase of recovery and was significantly higher after 48 h of recovery after rehydrating with DMW compared with plain water. Conclusions DMW with moderate mineralization was more effective in inducing recovery of aerobic capacity and leg muscle power compared with plain water following prolonged dehydrating aerobic running exercise. PMID:25002835

  12. Antidepressants and ejaculation: a double-blind, randomized, placebo-controlled, fixed-dose study with paroxetine, sertraline, and nefazodone.

    PubMed

    Waldinger, M D; Zwinderman, A H; Olivier, B

    2001-06-01

    Antidepressant medication is often associated with sexual side effects. A double-blind, placebo-controlled study in men with lifelong rapid ejaculation was performed to assess the effects of two selective serotonin (5-HT) reuptake inhibitors--paroxetine and sertraline--and the 5-HT2 antagonist and 5-HT/noradrenaline reuptake inhibitor nefazodone on the latency to ejaculate. Forty-eight men with an intravaginal ejaculation latency time (IELT) of a maximum of 1 minute were randomly assigned to receive paroxetine (20 mg/day), sertraline (50 mg/day), nefazodone (400 mg/day), or placebo for 6 weeks. During the 1-month baseline and 6-week treatment period, IELTs were measured at home with a stopwatch. The trial was completed by 40 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was stable at approximately 20 seconds. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.002); the IELT after paroxetine and sertraline gradually increased to approximately 146 and 58 seconds, respectively, compared with 28 seconds in the nefazodone group. The paroxetine and sertraline groups differed significantly (p < 0.001 and p = 0.024, respectively) from placebo, but the nefazodone group did not (p = 0.85). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, whereas sertraline delayed it only moderately. There was no clinically relevant delay in ejaculation with nefazodone. PMID:11386492

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

    PubMed

    Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

    2016-01-01

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

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

    PubMed Central

    Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

    2015-01-01

    The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood. PMID:26870678

  15. Paroxetine Controlled Release for Premenstrual Dysphoric Disorder: Remission Analysis Following a Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Pearlstein, Teri B.; Bellew, Kevin M.; Endicott, Jean; Steiner, Meir

    2005-01-01

    Objective: To compare the efficacy and safety of paroxetine controlled release (CR) (12.5 mg/day or 25 mg/day) versus placebo in premenstrual dysphoric disorder (PMDD). Method: A double-blind, randomized, placebo-controlled trial was conducted over 3 menstrual cycles in women aged 18–45 years with confirmed DSM-IV PMDD in 47 outpatient centers across the United States and Canada from November 1999 to January 2002. The primary efficacy measure was the visual analog scale (VAS)-Mood, which is the mean of 4 core symptoms: irritability, tension, depressed mood, and affective lability. Results: A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = −12.58 mm, 95% CI = −18.40 to −6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = −7.51 mm, 95% CI = −13.40 to −1.62; p = .013). Paroxetine CR was generally well tolerated. Conclusion: Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated. PMID:15841196

  16. A double blind, randomized, placebo controlled clinical study evaluates the early efficacy of aflapin in subjects with osteoarthritis of knee.

    PubMed

    Vishal, Amar A; Mishra, Artatrana; Raychaudhuri, Siba P

    2011-01-01

    Aflapin(®) is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is more efficacious as an anti-inflammatory agent compared to the existing Boswellia products, 5-Loxin(®) and traditional 65% Boswellia extract. A 30-day, double-blind, randomized, placebo-controlled study was conducted to validate the efficacy of Aflapin(®) in the management of clinical symptoms of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN69643551). Sixty eligible OA subjects selected through screening were included in the study. The subjects received either 100 mg (n=30) of Aflapin(®) or placebo (n=30) daily for 30 days. Each subject was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 5, 15 and 30. A series of biochemical tests in serum, urine and hematological parameters established the safety of Aflapin. The observations suggest that Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Aflapin provided significant improvements in pain score and functional ability in as early as 5 days of treatment. In conclusion, our observations suggest that Aflapin is a safe, fast acting and effective alternative intervention in the management of OA. PMID:22022214

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

    PubMed Central

    Udani, Jay K

    2013-01-01

    Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults. Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale. Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P < 0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P < 0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported. Conclusions. Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood. PMID:24371452

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

    PubMed

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

    2015-10-01

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

  19. A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease.

    PubMed

    2013-01-01

    BACKGROUND Latrepirdine is an orally administered experimental small molecule that was initially developed as an antihistamine and subsequently was shown to stabilize mitochondrial membranes and function, which might be impaired in Huntington disease. OBJECTIVE To determine the effect of latrepirdine on cognition and global function in patients with mild to moderate Huntington disease. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Sixty-four research centers in Australia, Europe, and North America. PATIENTS Four hundred three patients with mild to moderate Huntington disease and baseline cognitive impairment (Mini-Mental State Examination score, 10-26). INTERVENTION Latrepirdine (20 mg) vs matching placebo administered orally 3 times daily for 26 weeks. MAIN OUTCOME MEASURES The co-primary outcome measures were cognition as measured by the change in Mini-Mental State Examination score from baseline to week 26 and global function at week 26 as measured by the Clinician Interview-Based Impression of Change, plus carer interview, which ranges from 1 (marked improvement) to 7 (marked worsening). Secondary efficacy outcome measures included behavior, daily function, motor function, and safety. RESULTS The mean change in Mini-Mental State Examination score among participants randomized to latrepirdine (1.5-point improvement) did not differ significantly from that among participants randomized to placebo (1.3-point improvement) (P=.39). Similarly, the distribution of the Clinician Interview-Based Impression of Change, plus carer interview did not differ significantly among those randomized to latrepirdine compared with placebo (P=.84). No significant treatment effects were detected on the secondary efficacy outcome measures. The incidence of adverse events was similar between those randomized to latrepirdine (68.5%) and placebo (68.0%). CONCLUSION In patients with mild to moderate Huntington disease and cognitive impairment, treatment with

  20. Consumption of Sutherlandia frutescens by HIV-Seropositive South African Adults: An Adaptive Double-Blind Randomized Placebo Controlled Trial

    PubMed Central

    Williams, Karen; Gerkovich, Mary M.; Gqaleni, Nceba; Syce, James; Bartman, Patricia; Johnson, Quinton; Folk, William R.

    2015-01-01

    Background Sutherlandia frutescens (L.) R. Br. is widely used as an over the counter complementary medicine and in traditional medications by HIV seropositive adults living in South Africa; however the plant’s safety has not been objectively studied. An adaptive two-stage randomized double-blind placebo controlled study was used to evaluate the safety of consuming dried S. frutescens by HIV seropositive adults with CD4 T-lymphocyte count of >350 cells/μL. Methods In Stage 1 56 participants were randomized to S. frutescens 400, 800 or 1,200 mg twice daily or matching placebo for 24 weeks. In Stage 2 77 additional participants were randomized to either 1,200 mg S. frutescens or placebo. In the final analysis data from Stage 1 and Stage 2 were combined such that 107 participants were analysed (54 in the S. frutescens 1,200 mg arm and 53 in the placebo arm). Results S. frutescens did not change HIV viral load, and CD4 T-lymphocyte count was similar in the two arms at 24 weeks; however, mean and total burden of infection (BOI; defined as days of infection-related events in each participant) was greater in the S. frutescens arm: mean (SD) 5.0 (5.5) vs. 9.0 (12.7) days (p = 0.045), attributed to two tuberculosis cases in subjects taking isoniazid preventive therapy (IPT). Conclusion A possible interaction between S. frutescens and IPT needs further evaluation, and may presage antagonistic interactions with other herbs having similar biochemical (antioxidant) properties. No other safety issues relating to consumption of S. frutescens in this cohort were identified. Trial Registration ClinicalTrials.gov NCT00549523 PMID:26186450

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

    SciTech Connect

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

    2011-04-01

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

  2. Effect of Zolpidem on Sleep Quality of Professional Firefighters; a Double Blind, Randomized, Placebo-Controlled Crossover Clinical Trial.

    PubMed

    Mehrdad, Ramin; Sadeghniiat Haghighi, Khosro; Naseri Esfahani, Amir Hossein

    2015-01-01

    Professional firefighting is among the most demanding jobs. Prior studies have showed the notable prevalence of poor sleep quality among professional firefighters that may result in catastrophes. The aim of this study was in field confirmation of zolpidem usage (10 mg/PO/bed time) for short term management of poor sleeps quality among professional firefighters. In a double-blind, randomized, placebo-controlled crossover clinical trial among professional firefighters, 27 poor sleepers were assigned randomly to one of the two groups. Two 14 days experimental periods were separated by a 14-day washout phase. Sleep quality was assessed using the Persian version of Pittsburgh Sleep Quality Index (PSQI). Six of the 27 enrolled voluntaries dropped out. Two rare side effects of zolpidem occurred in the study. A significant improvement of the PSQI score was detected in zolpidem period versus placebo in both groups (7.14 ± 3.02 vs 12.38 ± 2.51, P<0.001) although zolpidem had no significant effect on time of waking up (6.76 ± 1.21 vs.6.64 ± 1.27, P=0.89). Zolpidem significantly improved all components of PSQI (Subjective sleep quality, Sleep latency, Sleep duration, Habitual sleep efficiency, Sleep disturbances and Daytime dysfunction) in the current study except the use of sleep medication. Sleep onset latency was the component of PSQI with the greatest degree of abnormality among firefighters in a previous study. Interestingly, sleep latency was the component of PSQI with the most treatment effect of zolpidem in the current study. Zolpidem can be used asa part of treatment regimens in short time management of poor sleep quality among professional firefighters. PMID:26553086

  3. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial

    PubMed Central

    2012-01-01

    Background Axonal sensory peripheral neuropathy is the major dose-limiting side effect of paclitaxel.Omega-3 fatty acids have beneficial effects on neurological disorders from their effects on neurons cells and inhibition of the formation of proinflammatory cytokines involved in peripheral neuropathy. Methods This study was a randomized double blind placebo controlled trial to investigate the efficacy of omega-3 fatty acids in reducing incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN). Eligible patients with breast cancer randomly assigned to take omega-3 fatty acid pearls, 640 mg t.i.d during chemotherapy with paclitaxel and one month after the end of the treatment or placebo. Clinical and electrophysiological studies were performed before the onset of chemotherapy and one month after cessation of therapy to evaluate PIPN based on "reduced Total Neuropathy Score". Results Twenty one patients (70%) of the group taking omega-3 fatty acid supplement (n = 30) did not develop PN while it was 40.7%( 11 patients) in the placebo group(n = 27). A significant difference was seen in PN incidence (OR = 0.3, .95% CI = (0.10-0.88), p = 0.029). There was a non-significant trend for differences of PIPN severity between the two study groups but the frequencies of PN in all scoring categories were higher in the placebo group (0.95% CI = (−2.06 -0.02), p = 0.054). Conclusions Omega-3 fatty acids may be an efficient neuroprotective agent for prophylaxis against PIPN. Patients with breast cancer have a longer disease free survival rate with the aid of therapeutical agents. Finding a way to solve the disabling effects of PIPN would significantly improve the patients’ quality of life. Trial registration This trial was registered at ClinicalTrials.gov (NCT01049295) PMID:22894640

  4. An integral topical gel for cellulite reduction: results from a double-blind, randomized, placebo-controlled evaluation of efficacy

    PubMed Central

    Dupont, Eric; Journet, Michel; Oula, Marie-Laure; Gomez, Juan; Léveillé, Claude; Loing, Estelle; Bilodeau, Diane

    2014-01-01

    Background Cellulite is a serious cosmetic concern for most of the 90% of women affected by it. Objective To assess the clinical efficacy of a complex integral anti-cellulite gel. Methods This double-blind, randomized, placebo-controlled study involved 44 healthy women, aged 25–55 years. Subjects had a normal to slightly overweight body mass index and presented slight to moderate cellulite on their thighs, buttocks, and/or hips at baseline. Subjects were randomly assigned to either the treated or placebo group and accordingly applied the active product or placebo on their hips, stomach, buttocks, and thighs, twice daily for 3 months. Skin tonicity, orange-peel aspect, and stubborn cellulite were assessed at day 0, 28, 56, and 84. A self-evaluation questionnaire was completed by all volunteers. Results At the end of the study, an average of 81% of the subjects applying the active product presented improvement in their cellulite condition versus 32% for the placebo group (all descriptors and sites combined). At day 84, skin tonicity, orange-peel appearance, and stubborn cellulite were improved in a significant manner (P<0.05) over placebo, on all studied areas. Skin tonicity improved on average by +41% for buttocks, +35% for hips, and +31% for thighs. Orange peel appearance was reduced on average by −25% for buttocks, −22% for hips, and −22% for thighs. Stubborn cellulite was reduced on average by −19% for buttocks, −24% for hips, and −22% for thighs. Circumference measurements decreased in a significant manner (P<0.05) over placebo, for the abdomen (average value of −1.1 cm) and thighs (average value of −0.8 cm). The product was well tolerated and perceived by the volunteers themselves as better performing than placebo on all criteria. Conclusion All results validate the efficacy of the present integral formulation to significantly reduce signs of cellulite and reshape the silhouette. PMID:24600240

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

    PubMed Central

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

    2016-01-01

    Objective To test the efficacy of adjunctive ziprasidone in adults with non-psychotic unipolar major depression experiencing persistent symptoms following 8 weeks of open-label escitalopram. Method This was a multi-center, parallel randomized, double-blind, placebo-controlled trial conducted at three academic medical centers in the United States. The participant pool consisted of 139 outpatients with persistent symptoms of major depressive disorder following an 8-week open label trial of escitalopram (phase 1). Subjects were randomized (1:1, n=139) to adjunctive ziprasidone (escitalopram+ziprasidone, n=71) or adjunctive placebo (escitalopram+placebo, n=68), with 8 weekly follow-up assessments. Primary outcome was defined by clinical response according to the 17-item Hamilton Depression Rating Scale (HAMD-17) and determined by a 50% or greater reduction in scale scores. The Hamilton Anxiety Rating scale (HAM-A) and Visual Analogue Scale for Pain were defined a priori as key secondary outcome measures. Results Rates of clinical response (35.2% vs. 20.5%, p=0.04) and mean improvement in HAMD-17 total scores (−6.4 ± 6.4 vs. −3.3 ± 6.2, p=0.04) were significantly greater for the escitalopram+ziprasidone group. Several secondary measures of antidepressant efficacy were also in favor of adjunctive ziprasidone. Escitalopram+ziprasidone also resulted in significantly greater improvement in HAM-A, but not Visual Analogue Scale for Pain scores. Ten (14%) patients discontinued escitalopram+ziprasidone due to intolerance versus none for escitalopram+placebo (p<0.01 versus placebo). Conclusions Adjunctive ziprasidone, when added to escitalopram, demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms following 8 weeks of open-label escitalopram. PMID:26085041

  6. Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial

    PubMed Central

    2013-01-01

    Background Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention. Methods Healthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score ≥ 3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping. Results One hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) = 0.69–1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR = 1.42, 95% CI = 0.90–2.25). Conclusions R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo. Trial registration ClinicalTrials.gov NCT01536288. PMID:24176010

  7. Symptomatic improvement with gluten restriction in irritable bowel syndrome: a prospective, randomized, double blinded placebo controlled trial

    PubMed Central

    Pawar, Sunil V; Gambhire, Pravir A; Jain, Samit S; Surude, Ravindra G; Shah, Vinaya B; Contractor, Qais Q; Rathi, Pravin M

    2016-01-01

    Background/Aims The existence of non-celiac gluten sensitivity has been debated. Indeed, the intestinal and extra-intestinal symptoms of many patients with irritable bowel syndrome (IBS) but without celiac disease or wheat allergy have been shown to improve on a gluten-free diet. Therefore, this study set out to evaluate the effects of gluten on IBS symptoms. Methods We performed a double-blind randomized placebo-controlled rechallenge trial in a tertiary care hospital with IBS patients who fulfilled the Rome III criteria. Patients with celiac disease and wheat allergy were appropriately excluded. The participants were administered a gluten-free diet for 4 weeks and were asked to complete a symptom-based questionnaire to assess their overall symptoms, abdominal pain, bloating, wind, and tiredness on the visual analog scale (0-100) at the baseline and every week thereafter. The participants who showed improvement were randomly assigned to one of two groups to receive either a placebo (gluten-free breads) or gluten (whole cereal breads) as a rechallenge for the next 4 weeks. Results In line with the protocol analysis, 60 patients completed the study. The overall symptom score on the visual analog scale was significantly different between the two groups (P<0.05). Moreover, the patients in the gluten intervention group scored significantly higher in terms of abdominal pain, bloating, and tiredness (P<0.05), and their symptoms worsened within 1 week of the rechallenge. Conclusions A gluten diet may worsen the symptoms of IBS patients. Therefore, some form of gluten sensitivity other than celiac disease exists in some of them, and patients with IBS may benefit from gluten restrictions. PMID:27799885

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

    PubMed

    Andresen, Sven R; Bing, Jette; Hansen, Rikke M; Biering-Sørensen, Fin; Johannesen, Inger L; Hagen, Ellen Merete; Rice, Andrew S C; Nielsen, Jørgen F; Bach, Flemming W; Finnerup, Nanna B

    2016-09-01

    Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide that is produced in many cells in the body, is thought to potentiate the action of endocannabinoids and to reduce pain and inflammation. This randomized, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation carried forward). Secondary outcomes included a per protocol analysis and effects on spasticity, evoked pain, sleep problems, anxiety, depression, and global impression of change. We randomized 73 individuals with neuropathic pain due to SCI, of which 5 had a major protocol violation, and thus 68 were included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (-0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity, insomnia, or psychological functioning. PEA was not associated with more adverse effects than placebo. PMID:27227691

  9. Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Yousefichaijan, Parsa; Cyrus, Ali; Dorreh, Fatemeh; Rafeie, Mohammad; Sharafkhah, Mojtaba; Frohar, Faryar; Safi, Fatemeh

    2015-01-01

    Background: Nephrolithiasis in children is associated with a high rate of complications and recurrence. Objectives: Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. Results: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group. Conclusions: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field. PMID:26635934

  10. A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington's disease.

    PubMed

    López-Sendón Moreno, Jose Luis; García Caldentey, Juan; Trigo Cubillo, Patricia; Ruiz Romero, Carolina; García Ribas, Guillermo; Alonso Arias, M A Alonso; García de Yébenes, María Jesús; Tolón, Rosa María; Galve-Roperh, Ismael; Sagredo, Onintza; Valdeolivas, Sara; Resel, Eva; Ortega-Gutierrez, Silvia; García-Bermejo, María Laura; Fernández Ruiz, Javier; Guzmán, Manuel; García de Yébenes Prous, Justo

    2016-07-01

    Huntington's disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex(®), a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex(®) and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex(®) as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex(®) is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations.Clincaltrals.gov identifier: NCT01502046. PMID:27159993

  11. A Randomized, Double, Blind, Placebo, Controlled Trial of Venlafaxine for the Treatment of Depressed Cocaine-Dependent Patients

    PubMed Central

    Raby, Wilfrid Noel; Rubin, Eric A.; Garawi, Fatima; Cheng, Wendy; Mason, Ella; Sanfilippo, Lisa; Lord, Stephanie; Bisaga, Adam; Aharonovich, Efrat; Levin, Frances; McDowell, David; Nunes, Edward V.

    2014-01-01

    Objective This study tested the hypothesis that the antidepressant venlafaxine would be an effective treatment for cocaine abusers with concurrent depressive disorders. Methods This was a randomized, 12-week, double-blind, placebo-controlled trial of outpatients (N = 130) meeting DSM-IIIR criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with venlafaxine, up to 300 mg/day versus placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included Clinical Global Impression Scale (CGI), self-reported cocaine use, urine toxicology and the Hamilton Depression Scale (Ham-D). Results Mood response, defined as a 50% reduction in the Ham-D between randomization and end of study, was 41% (26/64) on venlafaxine, and 33% (22/66) on placebo (p = .39). Measures of depression (Ham-D and CGI) improved more rapidly on venlafaxine than placebo, but these differences disappeared by weeks 6–8. Cocaine outcomes did not differ between treatment groups, and the proportion of patients achieving three or more consecutive weeks of urine-confirmed abstinence was low (venlafaxine: 16%; placebo: 15%). Reduction in cocaine use was associated with mood response. Conclusions Overall, venlafaxine was not superior to placebo on either mood or cocaine use outcomes. Mood improvement was associated with improvement in cocaine use. However, placebo mood response was only moderate, and the proportion of patients achieving sustained abstinence was low. This suggests that the subgroup of cocaine-dependent patients with depressive disorders is relatively treatment resistant, and that further research is needed to improve outcomes for these patients. PMID:24313244

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

    PubMed Central

    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

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

    PubMed

    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

  14. A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression

    PubMed Central

    Brown, E Sherwood; Park, John; Marx, Christine E; Hynan, Linda S; Gardner, Claire; Davila, Domingo; Nakamura, Alyson; Sunderajan, Prabha; Lo, Alexander; Holmes, Traci

    2014-01-01

    Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology—Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ2(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=−0.43, p=0.036) and pregNANolone (r(22)=−0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered. PMID:24917198

  15. Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial

    PubMed Central

    Fleischer, David M.; Burks, A. Wesley; Vickery, Brian P.; Scurlock, Amy M.; Wood, Robert A.; Jones, Stacie M.; Sicherer, Scott H.; Liu, Andrew H.; Stablein, Donald; Henning, Alice K.; Mayer, Lloyd; Lindblad, Robert; Plaut, Marshall; Sampson, Hugh A.

    2012-01-01

    Background There are presently no available therapeutic options for peanut-allergic patients. Objective To investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT). Methods After a baseline oral food challenge (OFC) of up to 2g of peanut powder (~50% protein) (median successfully consumed dose [SCD] 46mg), 40 subjects, aged 12–37 (median 15) years, were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5g OFC was performed after 44 weeks followed by unblinding; placebo subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5g OFC. Week 44 OFCs from both groups were compared to baseline OFCs; subjects successfully consuming 5g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. Results After 44 weeks of SLIT, 14/20 (70%) subjects receiving peanut SLIT were responders compared to 3/20 (15%) subjects receiving placebo (p<0.001). In peanut-SLIT responders, median SCD increased from 3.5mg to 496mg. After 68 weeks of SLIT, median SCD significantly increased to 996mg (compared to week 44, p=0.05). The median SCD at the Week 44 crossover OFC was significantly higher than baseline (603mg vs 71mg; p=0.02). 7/16 (44%) crossover subjects were responders; median SCD increased from 21mg to 496mg among responders. Of 10,855 peanut doses through Week 44 OFCs, 63.1% were symptom-free; excluding oral/pharyngeal symptoms, 95.2% were symptom-free. Conclusions Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared to placebo. Longer duration of therapy showed statistically significant increases in the SCD. PMID:23265698

  16. Frovatriptan is Effective and Well Tolerated in Korean Migraineurs: A Double-Blind, Randomized, Placebo-Controlled Trial

    PubMed Central

    Moon, Heui-Soo; Chu, Min Kyung; Park, Jeong Wook; Oh, Kyungmi; Chung, Jae Myun; Cho, Yong Jin; Kim, Eung Gyu; Do, Jin Kuk; Jung, Hyong Gi

    2010-01-01

    Background and Purpose Frovatriptan is a selective 5-HT1B/1D agonist with a long duration of action and a low incidence of side effects. Although several placebo-controlled trials have documented the clinical efficacy and safety of frovatriptan in adults with migraine, this drug has not previously been studied in Asian including Korean patients. Methods In this double-blind multicenter trial, 229 patients with migraine were randomized to receive frovatriptan 2.5 mg or placebo upon the occurrence of a moderate-to-severe migraine. The primary outcome was the 2-hour headache response rate. Results Frovatriptan significantly increased the 2-hour headache response rate compared with placebo (52.9% vs. 34.0%, p=0.004). The headache response rates at 4, 6, and 12 hours were significantly higher in the frovatriptan group than in the placebo group, as was the pain-free rate at 2 hours (19.0% vs. 5.7%, p=0.004), 4 hours (40.7% vs. 23.0%, p=0.006), and 6 hours (56.1% vs. 34.0%, p=0.002). The median time to a headache response was significantly shorter in the frovatriptan group than in the placebo group (2.00 hours vs. 3.50 hours, p<0.001). The use of rescue medications was more common in the placebo group (p=0.005). Chest tightness associated with triptan was infrequent (2.5%), mild, and transient. Conclusions These results demonstrate that 2.5-mg frovatriptan is effective and well tolerated in Korean migraineurs for acute treatment of migraine attacks. PMID:20386640

  17. IQP-GC-101 Reduces Body Weight and Body Fat Mass: A Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Chong, Pee-Win; Beah, Zhi-Ming; Grube, Barbara; Riede, Linda

    2014-01-01

    IQP-GC-101 is a patented blend of the standardized extracts of Garcinia cambogia, Camellia sinensis, unroasted Coffea arabica, and Lagerstroemia speciosa. These individual ingredients of IQP-GC-101 have each shown promise in promoting weight loss; however, the efficacy of the blend has not been established. This randomized, placebo-controlled, double-blind, parallel group study conducted over 14 weeks (including a 2-week run-in phase) aimed to investigate the efficacy and safety of IQP-GC-101 in reducing body weight and body fat mass in overweight Caucasian adults. Subjects took three IQP-GC-101 or placebo tablets, twice a day, 30 min before main meals. All subjects also adhered to a 500 kcal/day energy deficit diet with 30% of energy from fat. Ninety-one overweight and mildly obese subjects (46 in the IQP-GC-101 group, 45 in the placebo group) completed the study. After 12-week intervention, IQP-GC-101 resulted in a mean (±SD) weight loss of 2.26 ± 2.37 kg compared with 0.56 ± 2.34 kg for placebo (pU = 0.002). There was also significantly more reduction in body fat mass, waist circumference, and hip circumference in the IQP-GC-101 group. No serious adverse events were reported. The use of IQP-GC-101 has been shown to result in body weight and body fat reduction in the current study, with good tolerability. © 2014 InQpharm Group Sdn Bhd. Phytotherapy Research published by John Wiley & Sons, Ltd. PMID:24797657

  18. Randomized, double-blind, placebo-controlled trial of spironolactone for hypokalemia in continuous ambulatory peritoneal dialysis patients.

    PubMed

    Yongsiri, Somchai; Thammakumpee, Jiranuch; Prongnamchai, Suriya; Tengpraettanakorn, Pechngam; Chueansuwan, Rachaneeporn; Tangjaturonrasme, Siriporn; Dinchuthai, Pakaphan

    2015-02-01

    The incidence of hypokalemia in continuous ambulatory peritoneal dialysis (CAPD) patients is about 15-60%, leading to significant complications. There is no standard treatment other than potassium supplement in this setting. The aim of this study was to evaluate effect of spironolactone 25 mg/day in CAPD patients who have a history of hypokalemia. This is a randomized, double-blind, placebo-controlled, cross-over study in CAPD patients who had a history of hypokalemia. Study intervention is 4 weeks of oral spironolactone 25 mg/day or placebo, cross-over after a 2-week wash-out period. The primary outcome was the difference of serum potassium before and after 4 weeks of spironolactone treatment. Serum potassium was measured every 2 weeks, serum magnesium, urine and peritoneal fluid potassium measured before and after each treatment period. We enrolled 24 patients, and 20 completed the cross-over study. Ten patients were anuric. The total doses of potassium supplement were the same during the study period. Serum potassium levels before and after study intervention were not significantly different in both groups (4.23 ± 0.64 vs. 3.90 ± 0.59 mEq/L for spironolactone P = 0.077 and 3.84 ± 0.62 vs. 3.91 ± 0.52 for placebo P = 0.551). Total 24-h potassium, magnesium, sodium excretion, urine volume and ultrafiltration volume were not affected by spironolactone or placebo. There was one episode of hyperkalemia (5.6 mEq/L) during the spironolactone treatment period. Spironolactone 25 mg/day does not have a significant effect on serum potassium or urine and peritoneal excretion rate in CAPD patients who have a history of hypokalemia.

  19. A randomized, double-blind, placebo-controlled trial of injected capsaicin for pain in Morton's neuroma.

    PubMed

    Campbell, Claudia M; Diamond, Eric; Schmidt, William K; Kelly, Margaret; Allen, Robert; Houghton, William; Brady, Kerrie L; Campbell, James N

    2016-06-01

    Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. The pain can be severe and especially problematic with walking. Treatment options are limited and surgery may lead to permanent numbness in the toes. Capsaicin, the pungent ingredient of hot peppers, produces analgesia by inducing retraction of nociceptive afferents from the area of innervation and is effective in treating certain neuropathic pain disorders. A randomized double-blind placebo-controlled study was conducted to test the efficacy, tolerability, and safety of a single 0.1 mg dose of capsaicin vs placebo injected into the region of the neuroma. A total of 58 subjects diagnosed with Morton's neuroma with foot pain ≥4 (0-10 numerical pain rating scale) were injected with 2 mL of lidocaine into the intermetatarsal space proximal to the neuroma to provide local anesthesia. After 5 minutes, 0.1 mg capsaicin or placebo was injected into the intermetatarsal space containing the painful neuroma. Average foot pain was rated for 2 weeks before through 4 weeks after injection. At weeks 1 and 4, the decrease in pain was significantly greater in the subjects treated with capsaicin (P = 0.021 and P = 0.019, respectively). A trend toward significance was noted at weeks 2 and 3. Improvements in functional interference scores and reductions in oral analgesic use were also seen in the capsaicin-treated group. These findings suggest that injection of capsaicin is an efficacious treatment option for patients with painful intermetatarsal neuroma.

  20. Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIa study

    PubMed Central

    Hernández-Ojeda, Jaime; Román-Pintos, Luis Miguel; Rodríguez-Carrízalez, Adolfo Daniel; Troyo-Sanromán, Rogelio; Cardona-Muñoz, Ernesto Germán; Alatorre-Carranza, María del Pilar; Miranda-Díaz, Alejandra Guillermina

    2014-01-01

    Background Diabetic neuropathy affects 50%–66% of patients with diabetes mellitus. Oxidative stress generates nerve dysfunction by causing segmental demyelinization and axonal degeneration. Antioxidants are considered to be the only etiologic management for diabetic polyneuropathy, and statins such as rosuvastatin increase nitric oxide bioavailability and reduce lipid peroxidation. The aim of this study was to evaluate the antioxidant effect of rosuvastatin in diabetic polyneuropathy. Methods We conducted a randomized, double-blind, placebo-controlled Phase IIa clinical trial in patients with type 2 diabetes and diabetic polyneuropathy (DPN) stage ≥1b. We allocated subjects to two parallel groups (1:1) that received rosuvastatin 20 mg or placebo for 12 weeks. Primary outcomes were neuropathic symptom score, disability score, and nerve conduction studies, and secondary outcomes were glycemic control, lipid and hepatic profile, lipid peroxidation, and nerve growth factor beta (NGF-β) levels. Results Both groups were of similar age and duration since diagnosis of diabetes and DPN. We observed improvement of DPN in the rosuvastatin group from stage 2a (88.2%) to stage 1b (41.2%), improvement of neuropathic symptom score from 4.5±2 to 2.4±1.8, and significant (P=0.001) reductions of peroneal nerve conduction velocity (from 40.8±2.2 to 42.1±1.6 seconds) and lipid peroxidation (from 25.4±2 to 12.2±4.0 nmol/mL), with no significant change in glycemic control or β-NGF. Conclusion The severity, symptoms, and nerve conduction parameters of DPN improved after 12 weeks of treatment with rosuvastatin. These beneficial effects appear to be attributable to reductions in lipid peroxidation and oxidative stress. PMID:25214797

  1. A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal

    PubMed Central

    Rayamajhi, Ajit; Nightingale, Sam; Bhatta, Nisha Keshary; Singh, Rupa; Ledger, Elizabeth; Bista, Krishna Prasad; Lewthwaite, Penny; Mahaseth, Chandeshwar; Turtle, Lance; Robinson, Jaimie Sue; Galbraith, Sareen Elizabeth; Wnek, Malgorzata; Johnson, Barbara Wilmot; Faragher, Brian

    2015-01-01

    Background Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG’s anti-inflammatory properties may also be beneficial. Methodology/Principal Findings We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. Conclusions/Significance A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. Trial Registration ClinicalTrials.gov NCT01856205 PMID:25886645

  2. Lovastatin for the Treatment of Adult Patients With Dengue: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Whitehorn, James; Nguyen, Chau Van Vinh; Khanh, Lam Phung; Kien, Duong Thi Hue; Quyen, Nguyen Than Ha; Tran, Nguyen Thi Thanh; Hang, Nguyen Thuy; Truong, Nguyen Thanh; Hue Tai, Luong Thi; Cam Huong, Nguyen Thi; Nhon, Vo Thanh; Van Tram, Ta; Farrar, Jeremy; Wolbers, Marcel; Simmons, Cameron P.; Wills, Bridget

    2016-01-01

    Background. Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy. Methods. Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms. Results. Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures. Conclusions. We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe. Chinese Clinical Trials Registration. ISRCTN03147572. PMID:26565005

  3. Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

    SciTech Connect

    Burlage, Fred R. Roesink, Judith M.; Kampinga, Harm H.; Coppes, Rob P.; Terhaard, Chris; Langendijk, Johannes A.; Luijk, Peter van; 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 HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.

  4. IQP-GC-101 reduces body weight and body fat mass: a randomized, double-blind, placebo-controlled study.

    PubMed

    Chong, Pee-Win; Beah, Zhi-Ming; Grube, Barbara; Riede, Linda

    2014-10-01

    IQP-GC-101 is a patented blend of the standardized extracts of Garcinia cambogia, Camellia sinensis, unroasted Coffea arabica, and Lagerstroemia speciosa. These individual ingredients of IQP-GC-101 have each shown promise in promoting weight loss; however, the efficacy of the blend has not been established. This randomized, placebo-controlled, double-blind, parallel group study conducted over 14 weeks (including a 2-week run-in phase) aimed to investigate the efficacy and safety of IQP-GC-101 in reducing body weight and body fat mass in overweight Caucasian adults. Subjects took three IQP-GC-101 or placebo tablets, twice a day, 30 min before main meals. All subjects also adhered to a 500 kcal/day energy deficit diet with 30% of energy from fat. Ninety-one overweight and mildly obese subjects (46 in the IQP-GC-101 group, 45 in the placebo group) completed the study. After 12-week intervention, IQP-GC-101 resulted in a mean (±SD) weight loss of 2.26 ± 2.37 kg compared with 0.56 ± 2.34 kg for placebo (pU  = 0.002). There was also significantly more reduction in body fat mass, waist circumference, and hip circumference in the IQP-GC-101 group. No serious adverse events were reported. The use of IQP-GC-101 has been shown to result in body weight and body fat reduction in the current study, with good tolerability.

  5. Homeopathic remedy for arsenic toxicity?: Evidence-based findings from a randomized placebo-controlled double blind human trial.

    PubMed

    Belon, Philippe; Banerjee, Antara; Karmakar, Susanta Roy; Biswas, Surjyo Jyoti; Choudhury, Sandipan Chaki; Banerjee, Pathikrit; Das, Jayanta Kumar; Pathak, Surajit; Guha, Bibhas; Paul, Saili; Bhattacharjee, Nandini; Khuda-Bukhsh, Anisur Rahman

    2007-10-01

    Millions of people are at risk of groundwater arsenic contamination, but supply of arsenic-free drinking water is grossly inadequate. The present study was intended to examine if a potentized homeopathic remedy reportedly showing ameliorating potentials in people inhabiting high-risk arsenic-contaminated areas but drinking arsenic-free water, can also ameliorate arsenic toxicity in subjects living in high-risk arsenic-contaminated areas, and drinking arsenic-contaminated water. This pilot study was conducted on 20 males and 19 females of village Dasdiya (arsenic contaminated) who initially agreed to act as volunteers; but as many as 14, mostly placebo-fed subjects, later dropped out. 18 volunteers, 14 males and 4 females, from a distant village, Padumbasan (arsenic-free), served as negative controls. In a double blind placebo-controlled study, a potentized remedy of homeopathic Arsenicum Album-30 and its placebo (Succussed Alcohol-30) were given randomly to volunteers. Arsenic contents in urine and blood and several widely accepted toxicity biomarkers and pathological parameters in blood were analyzed before and after 2 months of administration of either verum or placebo. Elevated levels of ESR, creatinine and eosinophils and increased activities of AST, ALT, LPO and GGT were recorded in arsenic exposed subjects. Decreased levels of hemoglobin, PCV, neutrophil percentages, and GSH content and low G-6-PD activity were also observed in the arsenic exposed people. The administration of "verum" appeared to make positive modulations of these parameters, suggestive of its ameliorative potentials. Most of the subjects reported better appetite and improvement in general health, thereby indicating possibility of its use in remote arsenic-contaminated areas as an interim health support measure to a large population at risk.

  6. Creatine supplementation and resistance training in vulnerable older women: a randomized double-blind placebo-controlled clinical trial.

    PubMed

    Gualano, Bruno; Macedo, André Regis; Alves, Christiano Robles Rodrigues; Roschel, Hamilton; Benatti, Fabiana Braga; Takayama, Liliam; de Sá Pinto, Ana Lucia; Lima, Fernanda Rodrigues; Pereira, Rosa Maria Rodrigues

    2014-05-01

    This study aimed to examine the efficacy of creatine supplementation, associated or not with resistance training, in vulnerable older women. A 24-week, double-blind, randomized, placebo-controlled trial was performed. Sixty subjects were assigned to compose the following groups: placebo (PL), creatine supplementation (CR), placebo with resistance training (PL+RT), and creatine supplementation with resistance training (CR+RT). The subjects were assessed at baseline and after 24weeks. The primary outcome was muscle strength, as assessed by one-repetition maximum (1-RM) tests. Secondary outcomes included appendicular lean mass, bone mass, biochemical bone markers, and physical function tests. The changes in 1-RM leg press were significantly greater in the CR+RT group (+19.9%) than in the PL (+2.4%) and the CR groups (+3.7%), but not than in the PL+RT group (+15%) (p=0.002, p=0.002, and p=0.357, respectively). The CR+RT group showed superior gains in 1-RM bench press (+10%) when compared with all the other groups (p≤0.05). The CR+RT group (+1.31%) showed greater appendicular lean mass accrual than the PL (-1.2%), the CR (+0.3%), and the PL+RT groups (-0.2%) (p≤0.05). The CR and the PL+RT groups experienced comparable gains in appendicular lean mass (p=0.62), but superior to those seen in the PL group. Changes in fat mass, bone mass and serum bone markers did not significantly differ between the groups (p>0.05). In conclusion, creatine supplementation combined with resistance training improved appendicular lean mass and muscle function, but not bone mass, in older vulnerable women. Clinicaltrials.gov: NCT01472393. PMID:24530883

  7. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus

    PubMed Central

    DeVincenzo, John; Lambkin-Williams, Robert; Wilkinson, Tom; Cehelsky, Jeffrey; Nochur, Sara; Walsh, Edward; Meyers, Rachel; Gollob, Jared; Vaishnaw, Akshay

    2010-01-01

    RNA interference (RNAi) is a natural mechanism regulating protein expression that is mediated by small interfering RNAs (siRNA). Harnessing RNAi has potential to treat human disease; however, clinical evidence for the effectiveness of this therapeutic approach is lacking. ALN-RSV01 is an siRNA directed against the mRNA of the respiratory syncytial virus (RSV) nucleocapsid (N) protein and has substantial antiviral activity in a murine model of RSV infection. We tested the antiviral activity of ALN-RSV01 in adults experimentally infected with wild-type RSV. Eighty-eight healthy subjects were enrolled into a randomized, double-blind, placebo-controlled trial. A nasal spray of ALN-RSV01 or saline placebo was administered daily for 2 days before and for 3 days after RSV inoculation. RSV was measured serially in nasal washes using several different viral assays. Intranasal ALN-RSV01 was well tolerated, exhibiting a safety profile similar to saline placebo. The proportion of culture-defined RSV infections was 71.4 and 44.2% in placebo and ALN-RSV01 recipients, respectively (P = 0.009), representing a 38% decrease in the number of infected and a 95% increase in the number of uninfected subjects. The acquisition of infection over time was significantly lower in ALN-RSV01 recipients (P = 0.007 and P = 0.03, viral culture and PCR, respectively). Multiple logistic regression analysis showed that the ALN-RSV01 antiviral effect was independent of other factors, including preexisting RSV antibody and intranasal proinflammatory cytokine concentrations. ALN-RSV01 has significant antiviral activity against human RSV infection, thus establishing a unique proof-of-concept for an RNAi therapeutic in humans and providing the basis for further evaluation in naturally infected children and adults. PMID:20421463

  8. Clinical Evidence of Effects of Lactobacillus plantarum HY7714 on Skin Aging: A Randomized, Double Blind, Placebo-Controlled Study.

    PubMed

    Lee, Dong Eun; Huh, Chul-Sung; Ra, Jehyeon; Choi, Il-Dong; Jeong, Ji-Woong; Kim, Sung-Hwan; Ryu, Ja Hyun; Seo, Young Kyoung; Koh, Jae Sook; Lee, Jung-Hee; Sim, Jae-Hun; Ahn, Young-Tae

    2015-12-28

    The beneficial effects of probiotics are now widely reported, although there are only a few studies on their anti-aging effects. We have found that Lactobacillus plantarum HY7714 (HY7714) improves skin hydration and has anti-photoaging effects, and in the present study, we have further evaluated the anti-aging effect of HY7714 via a randomized, double blind, placebo-controlled clinical trial. The trial included 110 volunteers aged 41 and 59 years who have dry skin and wrinkles. Participants took 1 × 10(10) CFU/day of HY7714 (probiotic group) or a placebo (placebo group) for 12 weeks. Skin hydration, wrinkles, skin gloss, and skin elasticity were measured every 4 weeks during the study period. There were significant increases in the skin water content in the face (p < 0.01) and hands (p < 0.05) at week 12 in the probiotic group. Transepidermal water loss decreased significantly in both groups at weeks 4, 8, and 12 (p < 0.001 compared with baseline), and was suppressed to a greater extent in the face and forearm in the probiotic group at week 12. Volunteers in the probiotic group had a significant reduction in wrinkle depth at week 12, and skin gloss was also significantly improved by week 12. Finally, skin elasticity in the probiotic group improved by 13.17% (p < 0.05 vs. controls) after 4 weeks and by 21.73% (p < 0.01 vs. controls) after 12 weeks. These findings are preliminary confirmation of the anti-aging benefit to the skin of L. plantarum HY7714 as a nutricosmetic agent.

  9. Kiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled study.

    PubMed

    Ansell, Juliet; Butts, Christine A; Paturi, Gunaranjan; Eady, Sarah L; Wallace, Alison J; Hedderley, Duncan; Gearry, Richard B

    2015-05-01

    The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, double-blind, placebo-controlled study, we examined the effects of Actazin and Gold, kiwifruit-derived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14-day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were observed in stool form as determined by use of the Bristol stool scale. In a subgroup analysis of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the number of daily bowel movements by greater than 1 bowel movement per week. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup analysis of responders. This study demonstrated that Actazin and Gold produced clinically meaningful increases in bowel movements in healthy individuals.

  10. Effect of myrtle fruit syrup on abnormal uterine bleeding: a randomized double-blind, placebo-controlled pilot study

    PubMed Central

    2014-01-01

    Background Myrtle (Myrtus communis L.) has been used in the Iranian Traditional Medicine as a treatment for abnormal uterine bleeding-menometrorrhagia. The main aim of this study is to evaluate the effect of myrtle fruit syrup on abnormal uterine bleeding-menometrorrhagia. Methods A randomized, double-blind, placebo-controlled pilot study was conducted on 30 women suffering from abnormal uterine bleeding-menometrorrhagia. Treatment comprised of giving 15 ml oral myrtle syrup daily (5 ml three times a day) for 7 days starting from the onset of bleeding. The myrtle syrup along with placebo was repeated for 3 consecutive menstrual periods. Menstrual duration and number of used pads were recorded by the Pictorial Blood loss Assessment Chart at the end of each menstrual period. The quality of life was also evaluated using the menorrhagia questionnaire. Results The mean number of bleeding days significantly declined from 10.6 ± 2.7 days to 8.2 ± 1.9 days after 3 months treatment with the syrup (p = 0.01) and consequently the participants in the intervention group used fewer pads after 3 months (16.4 ± 10.7) compared with the number of pads used at the beginning of the treatment (22.7 ± 12.0, p = 0.01). Bleeding days and number of pads used by the participants in the placebo group did not change significantly. Also significant changes of quality of life scores were observed in the intervention group after 3 months compared to the baseline. Conclusion Myrtle syrup is introduced as a potential remedy for abnormal uterine bleeding-menometrorrhagia. PMID:24888316

  11. A Double-Blind, Randomized, Placebo-Controlled Trial of Escitalopram in the Treatment of Pediatric Depression

    ERIC Educational Resources Information Center

    Wagner, Karen Dineen; Jonas, Jeffrey; Findling, Robert L.; Ventura, Daniel; Saikali, Khalil

    2006-01-01

    Objective: Escitalopram is a selective serotonin reuptake inhibitor antidepressant indicated for use in adults. This trial examined the efficacy and safety of escitalopram in pediatric depression. Method: Patients (6-17 years old) with major depressive disorder were randomized to receive 8 weeks of double-blind flexibly dosed treatment with…

  12. Transcranial pulsed electromagnetic fields for multiple chemical sensitivity: study protocol for a randomized, double-blind, placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Multiple chemical sensitivity (MCS) is a chronic condition of unknown etiology. MCS is characterized by recurrent nonspecific symptoms from multiple organ systems in response to chemical exposures in concentrations that are normally tolerated by the majority of the population. The symptoms may have severe impact on patients’ lives, but an evidence-based treatment for the condition is nonexisting. The pathophysiology is unclarified, but several indicators point towards abnormal processing of sensory signals in the central nervous system. Pulsed electromagnetic fields (PEMF) offer a promising new treatment for refractory depression and can be targeted at the brain, thereby activating biochemical cell processes. Methods/Design In a parallel, randomized, double-blind, placebo-controlled trial conducted at the Danish Research Centre for Chemical Sensitivities, the effects of PEMF in MCS patients will be assessed using the Re5 Independent System. Based on sample size estimation, 40 participants will be randomized to either PEMF therapy or placebo. The allocation sequence will be generated by computer. All involved parties (that is, participants, investigators, the research nurse, and the statistician) will be blinded to group allocation. The participants will receive PEMF therapy or placebo applied transcranially 30 minutes twice a day for 7 days a week over 6 consecutive weeks. Outcomes will be measured at baseline, once weekly during treatment, post treatment, and at 2.5-month and 4.5-month follow-up according to a predefined timetable. The primary outcome will be a measurement of the impact of MCS on everyday life. The secondary outcomes will be measurements of MCS symptoms, psychological distress (stress, anxiety or depressive symptoms), capsaicin-induced secondary punctate hyperalgesia, immunological markers in serum, and quality of life. Discussion This trial will assess the effects of PEMF therapy for MCS. Currently, there is no treatment with a

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

    PubMed Central

    2012-01-01

    Background Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) – a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. Methods 78 men aged 25–50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator’s Global assessment and Subjects’ opinion. Results In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator’s global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject’s rating for tolerability of treatment was similar in both groups. Conclusions Vig

  14. Protective Effect of Folic Acid on Oxidative DNA Damage: A Randomized, Double-Blind, and Placebo Controlled Clinical Trial.

    PubMed

    Guo, Xiaojuan; Cui, Huan; Zhang, Haiyang; Guan, Xiaoju; Zhang, Zheng; Jia, Chaonan; Wu, Jia; Yang, Hui; Qiu, Wenting; Zhang, Chuanwu; Yang, Zuopeng; Chen, Zhu; Mao, Guangyun

    2015-11-01

    Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal.In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948.Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) = -0.88 (-1.62, -0.14) and P = 0.020 for low-FA; and β (95% confidence interval) = -2.68 (-3.42, -1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend < 0.001). Test of

  15. Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study123

    PubMed Central

    Velmurugan, Shanti; Gan, Jasmine Ming; Rathod, Krishnaraj S; Khambata, Rayomand S; Ghosh, Suborno M; Hartley, Amy; Van Eijl, Sven; Sagi-Kiss, Virag; Chowdhury, Tahseen A; Curtis, Mike; Kuhnle, Gunter GC; Wade, William G; Ahluwalia, Amrita

    2016-01-01

    Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo

  16. Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Trial

    PubMed Central

    Miskowiak, Kamilla W; Vinberg, Maj; Christensen, Ellen M; Bukh, Jens D; Harmer, Catherine J; Ehrenreich, Hannelore; Kessing, Lars V

    2014-01-01

    Pharmacological treatments for depression have insufficient efficacy in 30–40% of patients and fail to reverse cognitive deficits. Erythropoietin (EPO) has neurotrophic actions and aids neurocognitive function. The aim of this exploratory study was to determine whether recombinant human EPO improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ⩾17 were randomized to eight weekly EPO (Eprex; 40 000 IU) or saline infusions in a double-blind, placebo-controlled, parallel-group design. Patients were assessed at baseline and at weeks 5, 9, and 14. Primary outcome was reduction in HDRS-17 score. Global assessment of function (GAF) was reported in addition. Secondary outcome was remission rate, and tertiary outcomes were changes in Rey Auditory Verbal Learning Test (RAVLT), Beck Depression Inventory-21 (BDI-21), and World Health Organization Quality of life-BREF (WHOQOL-BREF). Exploratory outcomes were depression and cognition composite scores. HDRS-17, GAF, and remission rates showed no effects of EPO over saline at week 9 (P-value ⩾0.09). However, EPO improved BDI (P=0.02) and WHOQOL-BREF (P=0.01), and this was maintained at follow-up week 14 (P-values ⩽0.04). EPO enhanced verbal recall (P=0.02) and recognition (P=0.03), which was sustained at follow-up (P-values ⩽0.04). Exploratory analysis in patients fulfilling depression severity criteria at trial start revealed ameliorated HDRS-17 in EPO (N=14) vs saline groups (N=17), which was sustained at week 14 (P-values ⩽0.05). Exploratory analysis in the complete cohort showed that EPO reduced depression composite at weeks 9 and 14 (P-values=0.02). The findings of this exploratory study highlight EPO as an interesting compound for treatment-resistant depression, which deserves further investigation. PMID:24322509

  17. Homeopathy for Depression - DEP-HOM: study protocol for a randomized, partially double-blind, placebo controlled, four armed study

    PubMed Central

    2011-01-01

    Background Homeopathy is often sought by patients with depression. In classical homeopathy, the treatment consists of two main elements: the case history and the prescription of an individually selected homeopathic remedy. Previous data suggest that individualized homeopathic Q-potencies were not inferior to the antidepressant fluoxetine in a sample of patients with moderate to severe depression. However, the question remains whether individualized homeopathic Q-potencies and/or the type of the homeopathic case history have a specific therapeutical effect in acute depression as this has not yet been investigated. The study aims to assess the two components of individualized homeopathic treatment for acute depression, i.e., to investigate the specific effect of individualized Q-potencies versus placebo and to investigate the effect of different approaches to the homeopathic case history. Methods/Design A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2 × 2 factorial design with a six-week study duration per patient will be performed. 228 patients diagnosed with major depression (moderate episode) by a psychiatrist will be included. The primary endpoint is the total score on the 17-item Hamilton Depression Rating Scale after six weeks. Secondary end points are: Hamilton Depression Rating Scale total score after two and four weeks; response and remission rates, Beck Depression inventory total score, quality of life and safety at two, four and six weeks. Statistical analyses will be by intention-to-treat. The main endpoint will be analysed by a two-factorial analysis of covariance. Within this model generalized estimation equations will be used to estimate differences between verum and placebo, and between both types of case history. Discussion For the first time this study evaluates both the specific effect of homeopathic medicines and of a homeopathic case taking in patients with depression. It is an attempt to deal with the

  18. A randomized, double-blind, placebo-controlled clinical trial on the treatment of vitamin D insufficiency in postmenopausal women

    PubMed Central

    Hansen, Karen E.; Johnson, R. Erin; Chambers, Kaitlin R.; Johnson, Michael G.; Lemon, Christina C.; Thuy Vo, Tien Nguyen; Marvdashti, Sheeva

    2015-01-01

    Importance Experts debate optimal 25(OH)D levels for musculoskeletal health. Objective To compare effects of placebo, low-dose and high-dose vitamin D on one-year changes in total fractional calcium absorption, bone mineral density, Timed-Up-and-Go and 5-sit-to-stand tests and muscle mass in postmenopausal women with vitamin D insufficiency. Design Randomized, double-blind, placebo-controlled, clinical trial conducted from May 2010 to August 2014. Setting Single-center trial conducted in Madison, Wisconsin. Participants 230 postmenopausal women ≤75 years old with baseline 25(OH)D levels 14-27 ng/mL and no osteoporosis. Intervention Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=76), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels ≥30 ng/mL. Main Outcome Measures One year change in total fractional calcium absorption using two stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed-Up-and-Go and 5-Sit-to-Stand tests, functional status (Health Assessment Questionnaire) and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of p-values to control the false discovery rate. Results After controlling for baseline absorption, calcium absorption increased 1% (10 mg/day) in the high-dose arm, but decreased by 2% in low-dose (p=0.005 vs. high-dose) and by 1.3% placebo (p=0.03 vs. high-dose) arms. We found no between-arm changes in spine, mean total hip, mean femoral neck or total body bone mineral density, trabecular bone score, muscle mass, 5-sit-to-stand or Timed-Up-and-Go test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity or functional status. Conclusion and Relevance High-dose vitamin D therapy increased calcium absorption, but the

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

    PubMed

    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.

  20. Weight Maintenance with Litramine (IQP-G-002AS): A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

    PubMed Central

    Grube, Barbara; Chong, Pee-Win; Alt, Felix; Uebelhack, Ralf

    2015-01-01

    Background. Litramine (IQP-G-002AS) was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day) or a matching placebo. Primary endpoints were difference of mean body weight (kg) between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (−0.62 ± 1.55 kg versus 1.62 ± 1.48 kg, p < 0.001). More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387. PMID:26435849

  1. Effects of Dendropanax morbifera Léveille extracts on cadmium and mercury secretion as well as oxidative capacity: A randomized, double-blind, placebo-controlled trial

    PubMed Central

    SEO, JAE SAM; YOO, DAE YOUNG; JUNG, HYO YOUNG; KIM, DONG-WOO; HWANG, IN KOO; LEE, JONG YOUNG; MOON, SEUNG MYUNG

    2016-01-01

    In this randomized, double-blind, placebo controlled clinical trial, the effects of Dendropanax morbifera (D. morbifera) Léveille on heavy metal (cadmium and mercury) excretion as well as on lipid peroxidation and Cu, Zn-superoxide dismutase (SOD1) activity were investigated. For this study, tablets containing placebo or 300 mg of the leaf extract from D. morbifera Léveille were used. A total of 60 eligible healthy subjects were enrolled in this randomized, double-blind, placebo-controlled study. The differences in cadmium, mercury, and malondialdehyde (MDA) levels and SOD1 activity were measured in the serum 60 days after treatment with placebo or D. morbifera Léveille extracts. No significant differences between baseline characteristics and biochemical values were identified in subjects in the placebo and D. morbifera Léveille groups. Serum levels of cadmium, mercury and MDA decreased following consumption of D. morbifera Léveille extracts; however, no significant differences were identified. In addition, female, but not male, subjects who consumed D. morbifera Léveille extracts showed a significant increase in SOD1 activity. This result suggests that chronic consumption of D. morbifera Léveille extract can help to facilitate excretion of cadmium and mercury from serum and increase the antioxidant capacity in humans. PMID:27123258

  2. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial.

    PubMed

    Durgam, Suresh; Earley, Willie; Li, Rui; Li, Dayong; Lu, Kaifeng; Laszlovszky, István; Fleischhacker, W Wolfgang; Nasrallah, Henry A

    2016-10-01

    Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3-9mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9mg/d) or placebo for double-blind treatment (up to 72weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n=99) or cariprazine (n=101). Time to relapse was significantly longer in cariprazine- versus placebo-treated patients (P=.0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI]=0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥10% of patients during open-label treatment; there were no cariprazine adverse events ≥10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060.

  3. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial.

    PubMed

    Durgam, Suresh; Earley, Willie; Li, Rui; Li, Dayong; Lu, Kaifeng; Laszlovszky, István; Fleischhacker, W Wolfgang; Nasrallah, Henry A

    2016-10-01

    Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3-9mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9mg/d) or placebo for double-blind treatment (up to 72weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n=99) or cariprazine (n=101). Time to relapse was significantly longer in cariprazine- versus placebo-treated patients (P=.0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI]=0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥10% of patients during open-label treatment; there were no cariprazine adverse events ≥10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. PMID:27427558

  4. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study.

    PubMed

    Sarris, Jerome; Stough, Con; Bousman, Chad A; Wahid, Zahra T; Murray, Greg; Teschke, Rolf; Savage, Karen M; Dowell, Ashley; Ng, Chee; Schweitzer, Isaac

    2013-10-01

    Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. γ-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders-diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ≤ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava.

  5. Salacia Extract Improves Postprandial Glucose and Insulin Response: A Randomized Double-Blind, Placebo Controlled, Crossover Study in Healthy Volunteers

    PubMed Central

    Jeykodi, Shankaranarayanan; Deshpande, Jayant

    2016-01-01

    Thirty-five healthy subjects were randomly assigned to different doses of Salacia chinensis extract (200 mg, 300 mg, and 500 mg SCE) capsules and compared with placebo. It is a placebo controlled randomized crossover design study. Subjects were given oral sucrose solution along with capsules and plasma glucose and insulin responses were analyzed. Blood samples were collected at 0, 30, 60, 90, 120, and 180 minutes after administration. AUC insulin significantly lowered after ingestion of SCE. No significant adverse events were observed. Reducing glucose and insulin is very important in reducing postprandial hyperglycemia. PMID:27803937

  6. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial.

    PubMed

    Guekht, Alla B; Moessler, Herbert; Novak, Philipp H; Gusev, Evgenyi I

    2011-01-01

    No drug to treat vascular dementia (VaD) has yet been approved by the American or European authorities, leaving a large population of patients without effective therapy. Cerebrolysin has a long record of safety and might be efficacious in this condition. We conducted a large, multicenter, double-blind, placebo-controlled study in 242 patients meeting the criteria for VaD. The primary endpoint was the combined outcome of cognition (based on Alzheimer's Disease Assessment Scale Cognitive Subpart, Extended Version [ADAS-cog+] score) and overall clinical functioning (based on Clinician's Interview-Based Impression of Change plus Caregiver Input [CIBIC+] score) assessed after 24 weeks of treatment. Intravenous Cerebrolysin 20 mL was administered once daily over the course of 2 treatment cycles as add-on therapy to basic treatment with acetylsalicylic acid. The addition of Cerebrolysin was associated with significant improvement in both primary parameters. At week 24, ADAS-cog+ score improved by 10.6 points in the Cerebrolysin group, compared with 4.4 points in the placebo group (least squares mean difference, -6.17; P < .0001 vs placebo). CIBIC+ showed a mean improvement of 2.84 in the treatment arm and 3.68 in the placebo arm, a treatment difference of 0.84 (P < .0001 vs placebo). These findings were confirmed by responder analyses demonstrating higher rates in the Cerebrolysin group (ADAS-cog+ improvement of ≥4 points from baseline, 82.1% vs 52.2%; CIBIC+ score of <4 at week 24, 75.3% vs 37.4%; combined response in ADAS-cog+ and CIBIC+, 67.5% vs 27.0%). For Cerebrolysin, the odds ratio for achieving a favorable CIBIC+ response was 5.08 (P < .05), and that for achieving a favorable combined response was 5.63 (P < .05). Our data indicate that the addition of Cerebrolysin significantly improved clinical outcome, and that the benefits persisted for at least 24 weeks. Cerebrolysin was safe and well tolerated.

  7. Interventions That Affect Gastrointestinal Motility in Hospitalized Adult Patients: A Systematic Review and Meta-Analysis of Double-Blind Placebo-Controlled Randomized Trials.

    PubMed

    Asrani, Varsha M; Yoon, Harry D; Megill, Robin D; Windsor, John A; Petrov, Maxim S

    2016-02-01

    Gastrointestinal (GI) dysmotility is a common complication in acute, critically ill, postoperative, and chronic patients that may lead to impaired nutrient delivery, poor clinical, and patient-reported outcomes. Several pharmacological and nonpharmacological interventions to treat GI dysmotility were investigated in dozens of clinical studies. However, they often yielded conflicting results, at least in part, because various (nonstandardized) definitions of GI dysmotility were used and methodological quality of studies was poor. While a universally accepted definition of GI dysmotility is yet to be developed, a systematic analysis of data derived from double-blind placebo-controlled randomized trials may provide robust data on absolute and relative effectiveness of various interventions as the study outcome (GI motility) was assessed in the least biased manner.To systematically review data from double-blind placebo-controlled randomized trials to determine and compare the effectiveness of interventions that affect GI motility.Three electronic databases (MEDLINE, SCOPUS, and EMBASE) were searched. A random effects model was used for meta-analysis. The summary estimates were reported as mean difference (MD) with the corresponding 95% confidence interval (CI).A total of 38 double-blind placebo-controlled randomized trials involving 2371 patients were eligible for inclusion in the systematic review. These studies investigated a total of 20 different interventions, of which 6 interventions were meta-analyzed. Of them, the use of dopamine receptor antagonists (MD, -8.99; 95% CI, -17.72 to -0.27; P = 0.04) and macrolides (MD, -26.04; 95% CI, -51.25 to -0.82; P = 0.04) significantly improved GI motility compared with the placebo group. The use of botulism toxin significantly impaired GI motility compared with the placebo group (MD, 5.31; 95% CI, -0.04 to 10.67; P = 0.05). Other interventions (dietary factors, probiotics, hormones) did not affect GI motility

  8. Botulinum toxin type A on oral health in treating sialorrhea in children with cerebral palsy: a randomized, double-blind, placebo-controlled study.

    PubMed

    Wu, Katie Pei-Hsuan; Ke, Jyh-Yuh; Chen, Chung-Yao; Chen, Chia-Ling; Chou, Ming-Yen; Pei, Yu-Cheng

    2011-07-01

    Intrasalivary gland injection of botulinum toxin type A is known to treat sialorrhea effectively in children with cerebral palsy. However, oral health may be compromised with escalating dose. In this randomized, double-blind, and placebo-controlled pilot trial, the authors aim to determine the therapeutic effect of low-dose, ultrasonography-controlled botulinum toxin type A injection to bilateral parotid and submandibular glands on oral health in the management of sialorrhea. Twenty children diagnosed with cerebral palsy were randomly assigned to 2 groups. The treatment group received botulinum toxin type A injections, whereas the control received normal saline in the same locations. The authors evaluated subjective drooling scales, salivary flow rate, and oral health (salivary compositions and cariogenic bacterial counts). A significant decrease was found in salivary flow rate at the 1- and 3-month follow-up in the botulinum toxin-treated group. The authors suggest that current protocol can effectively manage sialorrhea while maintaining oral health.

  9. Effects of a Topical Saffron (Crocus sativus L) Gel on Erectile Dysfunction in Diabetics: A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Mohammadzadeh-Moghadam, Hossein; Nazari, Seyed Mohammad; Shamsa, Ali; Kamalinejad, Mohammad; Esmaeeli, Habibollah; Asadpour, Amir Abbas; Khajavi, Abdoljavad

    2015-10-01

    Erectile dysfunction is a man's persistent or recurrent inability to achieve and maintain erection for a satisfactory sexual relationship. As diabetes is a major risk factor for erectile dysfunction, the prevalence of erectile dysfunction among diabetic men has been reported as 35% to 90%. This randomized, parallel-group, double-blind, placebo-controlled trial investigated the effects of a topical saffron (Crocus sativus L) gel on erectile dysfunction in diabetic men. Patients were randomly allocated to 2 equal groups (with 25 patients each). The intervention group was treated with topical saffron, and the control received a similar treatment with placebo. The 2 groups were assessed using the International Index of Erectile Function Questionnaire before the intervention and 1 month after the intervention. Compared to placebo, the prepared saffron gel could significantly improve erectile dysfunction in diabetic patients (P < .001). This preliminary evidence suggests that saffron can be considered as a treatment option for diabetic men with erectile dysfunction.

  10. A double-blind, placebo-controlled, randomized withdrawal study of lurasidone for the maintenance of efficacy in patients with schizophrenia

    PubMed Central

    Tandon, Rajiv; Cucchiaro, Josephine; Phillips, Debra; Hernandez, David; Mao, Yongcai; Pikalov, Andrei; Loebel, Antony

    2016-01-01

    Objective: To evaluate the effectiveness of lurasidone as maintenance treatment for schizophrenia. Method: Adults experiencing an acute exacerbation of schizophrenia initially received 12–24 weeks of open-label treatment with lurasidone (40–80 mg/d, flexibly dosed). Patients who maintained clinical stability for ⩾12 weeks were randomized in double-blind fashion to placebo or lurasidone (40–80 mg/d, flexibly dosed) for an additional 28-week treatment period. The primary efficacy endpoint was time to relapse (based on Kaplan–Meier survival analysis). Results: A total of 676 patients enrolled in the open-label phase; 285 met protocol-specified stabilization criteria and were randomized to lurasidone (N=144) or placebo (N=141). During the open-label phase, mean Positive and Negative Syndrome Scale total score decreased from 90.1 to 54.4 in patients who met clinical stability criteria and were randomized. In the double-blind phase, lurasidone significantly delayed time to relapse compared with placebo (log-rank test, p=0.039), reflecting a 33.7% reduction in risk of relapse (Cox hazard ratio (95% confidence interval), 0.663 (0.447–0.983); p=0.041). Probability of relapse at the double-blind week 28 endpoint (based on Kaplan–Meier analysis) was 42.2% in the lurasidone group and 51.2% in the placebo group. Minimal changes in weight, lipid, glucose, and prolactin were observed throughout the study. Conclusions: This multicenter, placebo-controlled, randomized withdrawal study demonstrated the efficacy of lurasidone for the maintenance treatment of patients with schizophrenia. PMID:26645209

  11. Dairy proteins and the response to pneumovax in senior citizens: a randomized, double-blind, placebo-controlled pilot study.

    PubMed

    Freeman, Samara L; Fisher, Laura; German, J Bruce; Leung, Patrick S; Prince, Harry; Selmi, Carlo; Naguwa, Stanley M; Gershwin, M Eric

    2010-03-01

    With the progressive aging of the world's population, immunosenescence is rapidly becoming a clinical concern as it accounts for a higher incidence of severe infections and poor response to vaccines. To identify nutritional approaches that may counteract immunosenescence is of obvious importance in clinical practice. Dairy products in general and whey proteins in particular share the capacity to stimulate the immune system within the digestive tract while the antibody response to Streptococcus pneumoniae vaccine is a good marker of the immune function. We performed a controlled, randomized, double-blind pilot study to determine if an eight-week supplementation with whey protein (or soy protein used as control) could enhance the serum response to pneumococcal vaccine in healthy senior citizens. Out of 127 volunteers, 17 subjects were eligible and completed the study receiving the vaccine after four weeks of supplementation. Antibody levels were measured at baseline and the end of the study against 14 pneumococcal types and a detailed nutritional questionnaire was administered to all subjects. Subjects receiving whey protein manifested a serum response higher compared to the control soy supplementation against 12/14 bacterial types. In particular, whey led to a higher frequency of response to all four more virulent types (4, 9, 14, and 23). Calorie and protein intake data suggest a better nutritional status in the whey group. Whey protein supplementation is a promising supplement to stimulate the immune response to vaccine in senior citizens and possibly to counteract immunosenescence while larger studies are warranted.

  12. Efficacy of a pre-thickened infant formula: a multicenter, double-blind, randomized, placebo-controlled parallel group trial in 104 infants with symptomatic gastroesophageal reflux.

    PubMed

    Vanderhoof, Jon A; Moran, J Roberto; Harris, Cheryl L; Merkel, Kimberly L; Orenstein, Susan R

    2003-01-01

    To evaluate a pre-thickened formula (Enfamil AR) for regurgitant gastroesophageal reflux, 104 infants were enrolled in a 5-week, multicenter, double-blind, randomized, placebo-controlled parallel group trial. The Enfamil AR group showed greater symptom reduction by the end of the first week: percent feedings with any regurgitation (p = 0.045), total regurgitation volume score (p = 0.035), and percent feedings with choke-gag-cough (p = 0.004). The most symptomatic infants at baseline had a reduction in trouble sleeping significantly with Enfamil AR by the end of the study (p = 0.030). This formula flows through a standard nipple, reduces regurgitation and choking-gagging-coughing within a week, and improves sleep in the most symptomatic babies by 5 weeks, without causing constipation.

  13. The effects of capsaicin topical therapy in dogs with atopic dermatitis: a randomized, double-blinded, placebo-controlled, cross-over clinical trial.

    PubMed

    Marsella, Rosanna; Nicklin, Constance F; Melloy, Caroline

    2002-06-01

    The efficacy of twice daily topical application of capsaicin (0.025%) for the management of pruritus in dogs with atopic dermatitis (AD) was evaluated in double-blinded, placebo-controlled study. Twelve dogs with AD were randomly assigned to either 0.025% capsaicin or vehicle lotion applied twice daily for 6 weeks. After a 4-week wash-out period, treatments were switched. Significant improvement was reported by owners (P = 0.0006), but not by investigators. Owners noted temporary worsening of pruritus after the first week of capsaicin therapy. Overall capsaicin was well tolerated. Substance P (SP) concentrations in the skin did not correlate with the severity of the pruritus and did not change significantly over time and between treatments. Lesional skin had less SP than nonlesional skin (P = 0.03). These observations suggest that topical capsaicin should be further evaluated as an adjunctive antipruritic agent in dogs with AD.

  14. In a double-blind, randomized and placebo-controlled trial, adjuvant allopurinol improved symptoms of mania in in-patients suffering from bipolar disorder.

    PubMed

    Jahangard, Leila; Soroush, Sara; Haghighi, Mohammad; Ghaleiha, Ali; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

    2014-08-01

    Allopurinol is a drug used primarily to treat hyperuricemia. In patients suffering from acute mania, increased levels of uric acid are observed, and symptom improvements are associated with decreased levels of uric acid. Accordingly, a purinergic dysfunction is plausibly a causative factor in the pathophysiology of mania. The aim of the present study was therefore to investigating whether allopurinol has benefits for patients treated with sodium valproate during acute mania. (Background) A double-blind, placebo-controlled study lasting 4 weeks was performed. The intention-to-treatment population included 57 patients; 50 concluded the study per protocol. Patients suffering from BPD and during acute mania were randomly assigned either to a treatment (sodium valproate 15-20 mg/kg+300 mg allopurinol twice a day) or to a control condition (sodium valproate 15-20 mg/kg+placebo). Experts rated illness severity and illness improvements (Clinical Global impression), and extent of mania via the Young Mania Rating scale. Uric acid levels were assessed at the beginning and end of the study. (Experimental procedures) Compared to the control group, symptoms of mania decreased significantly over time in the treatment group. Uric acid levels declined significantly in the treatment as compared to the control group. Probability of remission after 4 weeks was 23 times higher in the treatment than the control group. Lower uric acid levels after 4 weeks were associated with symptom improvements. (Results) The pattern of results from this double-blind, randomized and placebo-controlled study indicates that adjuvant allopurinol leads to significant improvements in patients suffering from acute mania (Conclusion). PMID:24953766

  15. Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Madsen, Michael Tvilling; Hansen, Melissa Voigt; Andersen, Lærke Toftegård; Hageman, Ida; Rasmussen, Lars Simon; Bokmand, Susanne; Rosenberg, Jacob; Gögenur, Ismail

    2016-01-01

    Study Objectives: To investigate whether administration of an oral dose of 6 mg melatonin before bedtime perioperatively in breast cancer surgery could change sleep outcomes measured by actigraphy. Methods: This paper reports secondary outcomes from a double-blind, placebo-controlled, randomized clinical trial where patients received 6 mg melatonin (n = 27) or placebo (n = 21) approximately 60 minutes before bedtime 3 nights preoperatively until at least one week postoperatively. Participants were monitored in the entire period with actigraphy, and were instructed to complete visual analogue scale (VAS) for sleep, and the Karolinska Sleepiness Scale (KSS) each morning. Results: Administration of 6 mg oral melatonin approximately 1 hour before bedtime resulted in significantly increased sleep efficiency and reduced wake after sleep onset for the entire 2-week postoperative period. No other significant differences for actigraphy determined sleep outcomes or subjective outcome parameters in the perioperative period were found between the groups. Overall, the patients sleep outcomes were within normal ranges and no participants had pathological sleep disturbances. Conclusions: Melatonin significantly changed sleep efficiency and wake after sleep onset after surgery, but had no effects on other objective sleep outcomes or on subjective sleep quality (VAS and KSS). Clinical Trial Registration: The trial was registered on www.clinicaltrials.gov (NCT01355523) before inclusion of the first patient. Citation: Madsen MT, Hansen MV, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I. Effect of melatonin on sleep in the perioperative period after breast cancer surgery: a randomized, double-blind, placebo-controlled trial. J Clin Sleep Med 2016;12(2):225–233. PMID:26414973

  16. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome

    PubMed Central

    Huang, Jehn-Yu; Yeh, Po-Ting; Hou, Yu-Chih

    2016-01-01

    Purpose To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). Methods A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer’s test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. Results Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti-SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer’s test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. Conclusion Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable-based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES. PMID:27274185

  17. Polyethylene glycol 3350 in occasional constipation: A one-week, randomized, placebo-controlled, double-blind trial

    PubMed Central

    McGraw, Thomas

    2016-01-01

    AIM: To evaluate the efficacy and safety of polyethylene glycol (PEG) 3350 in subjects with self-reported occasional constipation. METHODS: Eligible subjects ≥ 17 years of age were randomized to receive either placebo or PEG 3350 17 g once daily in this multicenter, double-blind trial. Evaluations were conducted before (baseline) and after a 7-d treatment period. The primary efficacy variable was the proportion of subjects reporting complete resolution of straining and hard or lumpy stools. Secondary efficacy variables assessed the severity of the subjects’ daily bowel movement (BM) symptoms, and preference of laxatives based on diary entries, visual analog scale scores, and questionnaires. RESULTS: Of the 203 subjects enrolled in the study, 11 had major protocol violations. Complete resolution was noted by 36/98 (36.7%) subjects in the PEG 3350 group and 23/94 (24.5%) in the placebo group (P = 0.0595). The number of complete BMs without straining or lumpy stools was similar between both groups. Subjects receiving PEG 3350 experienced significant relief in straining and reduction in hardness of stools over a 7-d period (P < 0.0001). Subjects reported that PEG 3350 had a better effect on their daily lives, provided better control over a BM, better relief from constipation, cramping, and bloating, and was their preferred laxative. Adverse events (AEs) were balanced between the PEG 3350 and the placebo groups. No deaths, serious AEs, or discontinuations due to AEs were reported. This trial is registered at clinicaltrials.gov as NCT00770432. CONCLUSION: Oral administration of 17 g PEG 3350 once daily for a week is effective, safe, and well tolerated in subjects with occasional constipation. PMID:27158544

  18. Effects of add-on mirtazapine on neurocognition in schizophrenia: a double-blind, randomized, placebo-controlled study.

    PubMed

    Stenberg, Jan-Henry; Terevnikov, Viatcheslav; Joffe, Marina; Tiihonen, Jari; Tchoukhine, Evgueni; Burkin, Mark; Joffe, Grigori

    2010-05-01

    Mirtazapine added to antipsychotics appears to improve the clinical picture of schizophrenia, including both negative and positive symptoms. This study explored the effect of adjunctive mirtazapine on neurocognition in patients with schizophrenia who had shown an insufficient response to first-generation antipsychotics (FGAs). Thirty-seven schizophrenia patients, who were at least moderately ill despite their FGA treatment, received add-on mirtazapine (n=19) or placebo (n=18) in a 6-wk double-blind, randomized trial. Widely used neuropsychological tests were performed to explore visual-spatial functions, verbal and visual memory, executive functions, verbal fluency and general mental and psychomotor speed. The data were analysed on the modified intent-to-treat basis with last observation carried forward. False discovery rate was applied to correct for multiple testing. Mirtazapine outperformed placebo in the domains of visual-spatial ability and general mental speed/attentional control as assessed by, correspondingly, Block Design and Stroop dots. The difference in the degree of change (i.e. change while on mirtazapine minus that on placebo) was 18.6% (p=0.044) and 11.1% (p=0.044), respectively. Adjunctive mirtazapine might offer a safe, effective and cost-saving option as a neurocognitive enhancer for FGA-treated schizophrenia patients. Mirtazapine+FGA combinations may become especially useful in light of the currently increasing attention towards FGAs. Larger and longer studies that incorporate functional outcomes, as well as comparisons with second-generation antipsychotics are, however, still needed for more definite conclusions. PMID:19941694

  19. Vilazodone in patients with generalized anxiety disorder: a double-blind, randomized, placebo-controlled, flexible-dose study

    PubMed Central

    Forero, Giovanna; Mathews, Maju; Nunez, Rene; Tang, Xiongwen; Durgam, Suresh; Sambunaris, Angelo

    2015-01-01

    Vilazodone is a selective serotonin reuptake inhibitor and a 5-HT1A receptor partial agonist that is approved for treatment of major depressive disorder in adults in the USA and Mexico. The efficacy, safety, and tolerability of vilazodone for generalized anxiety disorder (GAD) were investigated in a clinical trial (NCT01766401 ClinicalTrials.gov). Participants (18–70 years, inclusive) who met Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, criteria for GAD were randomized (1 : 1) to placebo or flexible-dose vilazodone (20–40 mg/day) for 8 weeks of double-blind treatment. Primary and secondary efficacy parameters were changes from baseline to week 8 in Hamilton Rating Scale for Anxiety and Sheehan Disability Scale total scores, respectively. Analysis was based on a mixed-effects model for repeated measures approach on the intent-to-treat population. The intent-to-treat population comprised 395 patients (placebo=197, vilazodone=198); 77% completed the study. The least squares mean difference in change from baseline to week 8 in the Hamilton Rating Scale for Anxiety total score was statistically significant for vilazodone versus placebo [−1.50 (−2.96, −0.04), P=0.0438]. The mean change from baseline to week 8 in the Sheehan Disability Scale total score for vilazodone versus placebo was not statistically significant. Adverse events were reported in 60% of placebo-treated and 83% of vilazodone-treated patients. This was a positive clinical trial of 20–40 mg/day vilazodone versus placebo in the treatment of GAD. PMID:26291335

  20. Influence of inhomogeneous static magnetic field-exposure on patients with erosive gastritis: a randomized, self- and placebo-controlled, double-blind, single centre, pilot study

    PubMed Central

    Juhász, Márk; Nagy, Viktor L.; Székely, Hajnal; Kocsis, Dorottya; Tulassay, Zsolt; László, János F.

    2014-01-01

    This pilot study was devoted to the effect of static magnetic field (SMF)-exposure on erosive gastritis. The randomized, self- and placebo-controlled, double-blind, pilot study included 16 patients of the 2nd Department of Internal Medicine, Semmelweis University diagnosed with erosive gastritis. The instrumental analysis followed a qualitative (pre-intervention) assessment of the symptoms by the patient: lower heartburn (in the ventricle), upper heartburn (in the oesophagus), epigastric pain, regurgitation, bloating and dry cough. Medical diagnosis included a double-line upper panendoscopy followed by 30 min local inhomogeneous SMF-exposure intervention at the lower sternal region over the stomach with peak-to-peak magnetic induction of 3 mT and 30 mT m−1 gradient at the target site. A qualitative (post-intervention) assessment of the same symptoms closed the examination. Sham- or SMF-exposure was used in a double-blind manner. The authors succeeded in justifying the clinically and statistically significant beneficial effect of the SMF- over sham-exposure on the symptoms of erosive gastritis, the average effect of inhibition was 56% by p = 0.001, n = 42 + 96. This pilot study was aimed to encourage gastroenterologists to test local, inhomogeneous SMF-exposure on erosive gastritis patients, so this intervention may become an evidence-based alternative or complementary method in the clinical use especially in cases when conventional therapy options are contraindicated. PMID:25008086

  1. Chinese Medicine Shensongyangxin Is Effective for Patients with Bradycardia: Results of a Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

    PubMed Central

    Liu, Yunfang; Li, Ning; Jia, Zhenhua; Lu, Feng; Pu, Jielin

    2014-01-01

    To evaluate the efficacy and safety of Shensong Yangxin (SSYX) in patients with bradycardia arrhythmias, a randomized, double-blind, and placebo-controlled study was conducted. Patients with bradycardia were randomly assigned to receive either SSYX (trial group, n = 115) or placebo (control group, n = 104) for 4 weeks. ECG, 24-hour continuous ECG recording, echocardiography, and hepatic and renal function were evaluated at baseline and after treatment. Results showed that the average heart rate, the fastest heart rate, and the lowest heart rate in the trial group were all significantly higher than those in the control group at the end of treatment (P < 0.05 or 0.01, resp.). Compared with pretreatment, the average heart rate, the fastest heart rate, and the lowest heart rate in the trial group all increased significantly after treatment (P < 0.05 or 0.01, resp.). Both the efficacy and the symptom scores in the trial group were significantly better than those in the control group after treatment (both having P < 0.01). No severe adverse effects were reported. In conclusion, SSYX treatment significantly increased the heart rate in patients with bradycardia without severe side effects. The exact mechanisms remain to be further explored. PMID:24527049

  2. Short-Term Soy Isoflavone Intervention in Patients with Localized Prostate Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Hamilton-Reeves, Jill M.; Banerjee, Snigdha; Banerjee, Sushanta K.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Kambhampati, Suman; Keighley, John; Van Veldhuizen, Peter

    2013-01-01

    Purpose We describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer. Methodology/Principal Findings We conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n = 42) or placebo (n = 44) for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM). Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant. Conclusions/Significance These data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA. Trial Registration ClinicalTrials.gov NCT00255125 PMID:23874588

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

    ERIC Educational Resources Information Center

    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. Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial†

    PubMed Central

    YaDeau, J. T.; Lin, Y.; Mayman, D. J.; Goytizolo, E. A.; Alexiades, M. M.; Padgett, D. E.; Kahn, R. L.; Jules-Elysee, K. M.; Ranawat, A. S.; Bhagat, D. D.; Fields, K. G.; Goon, A. K.; Curren, J.; Westrich, G. H.

    2015-01-01

    Background Pregabalin may reduce postoperative pain and opioid use. Higher doses may be more effective, but may cause sedation and confusion. This prospective, randomized, blinded, placebo-controlled study tested the hypothesis that pregabalin reduces pain at 2 weeks after total knee arthroplasty, but increases drowsiness and confusion. Methods Patients (30 per group) received capsules containing pregabalin (0, 50, 100, or 150 mg); two capsules before surgery, one capsule twice a day until postoperative day (POD) 14, one on POD15, and one on POD16. Multimodal analgesia included femoral nerve block, epidural analgesia, oxycodone–paracetamol, and meloxicam. The primary outcome was pain with flexion (POD14). Results Pregabalin did not reduce pain at rest, with ambulation, or with flexion at 2 weeks (P=0.69, 0.23, and 0.90, respectively). Pregabalin increased POD1 drowsiness (34.5, 37.9, 55.2, and 58.6% in the 0, 50, 100, and 150 mg arms, respectively; P=0.030), but did not increase confusion (0, 3.5, 0, and 3.5%, respectively; P=0.75). Pregabalin had no effect on acute or chronic pain, opioid consumption, or analgesic side-effects. Pregabalin reduced POD14 patient satisfaction [1–10 scale, median (first quartile, third quartile): 9 (8, 10), 8 (7, 10), 8 (5, 9), and 8 (6, 9.3), respectively; P=0.023). Protocol compliance was 63% by POD14 (50.0, 70.0, 76.7, and 56.7% compliance, respectively), with no effect of dose on compliance. Per-protocol analysis of compliant patients showed no effect of pregabalin on pain scores. Conclusions Pregabalin had no beneficial effects, but increased sedation and decreased patient satisfaction. This study does not support routine perioperative pregabalin for total knee arthroplasty patients. Clinical trial registration. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/study/NCT01333956. PMID:26170351

  5. Utility of intranasal Ketamine and Midazolam to perform gastric aspirates in children: a double-blind, placebo controlled, randomized study

    PubMed Central

    2014-01-01

    Background We performed a prospective, randomized, placebo-controlled study aimed to evaluate the efficacy and safety of a sedation protocol based on intranasal Ketamine and Midazolam (INKM) administered by a mucosal atomizer device in uncooperative children undergoing gastric aspirates for suspected tuberculosis. Primary outcome: evaluation of Modified Objective Pain Score (MOPS) reduction in children undergoing INKM compared to the placebo group. Secondary outcomes: evaluation of safety of INKM protocol, start time sedation effect, duration of sedation and evaluation of parents and doctors’ satisfaction about the procedure. Methods In the sedation group, 19 children, mean age 41.5 months, received intranasal Midazolam (0.5 mg/kg) and Ketamine (2 mg/kg). In the placebo group, 17 children received normal saline solution twice in each nostril. The child’s degree of sedation was scored using the MOPS. A questionnaire was designed to evaluate the parents’ and doctors’ opinions on the procedures of both groups. Results Fifty-seven gastric washings were performed in the sedation-group, while in the placebo-group we performed 51 gastric aspirates. The degree of sedation achieved by INMK enabled all procedures to be completed without additional drugs. The mean duration of sedation was 71.5 min. Mean MOPS was 3.5 (range 1-8) in the sedation-group, 7.2 (range 4-9) in the placebo-group (p <0.0001). The questionnaire revealed high levels of satisfaction by both doctors and parents in the sedation-group compared to the placebo-group. The only side effect registered was post-sedation agitation in 6 procedures in the sedation group (10.5%). Conclusions Our experience suggests that atomized INKM makes gastric aspirates more acceptable and easy to perform in children. Trial registration Unique trial Number: UMIN000010623; Receipt Number: R000012422. PMID:24598046

  6. Relapse Prevention in Pediatric Patients with ADHD Treated with Atomoxetine: A Randomized, Double-Blind, Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Michelson, David; Buitelaar, Jan K.; Danckaerts, Marina; Gillberg, Christopher; Spencer, Thomas J.; Zuddas, Alessandro; Faries, Douglas E.; Zhang, Shuyu; Biederman, Joseph

    2004-01-01

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

  7. Oral amrinone for the treatment of chronic congestive heart failure: results of a multicenter randomized double-blind and placebo-controlled withdrawal study.

    PubMed

    DiBianco, R; Shabetai, R; Silverman, B D; Leier, C V; Benotti, J R

    1984-11-01

    A placebo-controlled study was employed to evaluate the effects of oral amrinone in patients with congestive heart failure. After a baseline period of at least 4 weeks of standard treatment for refractory congestive heart failure, oral amrinone was added to the treatment regimen of 173 patients. Patients were predominantly male (89%), aged 24 to 76 years (mean 54), with ischemic (52%) or idiopathic (37%) dilated cardiomyopathy, in New York Heart Association functional class II (40%), III (59%) and IV (1%) and having a mean (+/- standard deviation) left ventricular ejection fraction of 25 +/- 15%. Phase 1: After the addition of amrinone (113 +/- 33 mg three times daily), 52 patients (30%) showed a maximal increase in treadmill exercise time exceeding 2 minutes (Naughton protocol), 72 (42%) had a lesser increase, 24 (14%) developed limiting adverse reactions, 20 (12%) died and 5 dropped out of the study. Fifty-two "responders" (30%) who were free of limiting side effects and had a greater than 2 minute increase in exercise time were randomized in double-blind fashion to continued amrinone or switched to placebo (each plus standard treatment) for an additional 12 weeks. Phase 2: Comparison of 31 of these 52 responders who continued to receive amrinone with the remaining 21 randomized to placebo revealed no significant differences in vital signs, indexes of left ventricular size and function, systolic time intervals or maximal exercise time. Continued follow-up study of patients receiving either amrinone or placebo revealed decreases in exercise times of 7 and 10%, respectively (both p less than 0.05 compared with before randomization). Episodes of worsened congestive heart failure severe enough to mandate termination of double-blind treatment were as frequent in patients taking placebo (4[18%] of 21) as in those taking amrinone (4[13%] of 31; p = NS). The average symptom score and functional class of each treatment group remained comparable. Adverse effects such as

  8. Pharmacogenetic study of the effects of raloxifene on negative symptoms of postmenopausal women with schizophrenia: A double-blind, randomized, placebo-controlled trial.

    PubMed

    Labad, Javier; Martorell, Lourdes; Huerta-Ramos, Elena; Cobo, Jesús; Vilella, Elisabet; Rubio-Abadal, Elena; Garcia-Pares, Gemma; Creus, Marta; Núñez, Cristian; Ortega, Laura; Miquel, Eva; Usall, Judith

    2016-10-01

    Several double-blind clinical trials have reported improvement in positive, negative and cognitive symptoms of schizophrenia with raloxifene, a selective receptor estrogen modulator. However, there are some inconsistencies in replicating findings between studies of different countries. The failure to replicate these findings may result from genetic factors that could explain some of the variability in the treatment response. However, pharmacogenetic studies exploring this topic in women with schizophrenia are lacking. We aimed to conduct an exploratory pharmacogenetic analysis of a double-blind, randomized, parallel, placebo-controlled study of 24 weeks' duration of raloxifene aiming to improve negative symptoms in postmenopausal women with schizophrenia. Four single nucleotide polymorphisms (SNPs) were studied: rs9340799, rs2234693 and rs1801132 in the Estrogen Receptor 1 (ESR1) gene, and rs1042597 in the UDP-glucuronosyltransferase 1A8 (UGT1A8) gene. Sixty-five postmenopausal women with schizophrenia (DSM-IV) were randomized to either 60mg/day adjunctive raloxifene (36 women) or adjunctive placebo (29 women). Psychopathological symptoms were assessed at baseline and at weeks 4, 12, and 24 with the Positive and Negative Syndrome Scale (PANSS). Of the four studied SNPs, the rs1042597 variant in the UGT1A8 gene was associated with a different treatment response in negative symptoms with raloxifene treatment, whereas the rs2234693 variant in the ESR1 gene was associated with a distinct response in general psychopathology. In conclusion, our study suggests that genetic variants in UGT1A8 and ESR1 genes modulate the treatment response to adding raloxifene to antipsychotic treatment in postmenopausal women with schizophrenia. PMID:27546373

  9. Antipsychotic Augmentation of Serotonin Reuptake Inhibitors in Treatment-Resistant Obsessive-Compulsive Disorder: An Update Meta-Analysis of Double-Blind, Randomized, Placebo-Controlled Trials

    PubMed Central

    Dold, Markus; Aigner, Martin; Lanzenberger, Rupert

    2015-01-01

    Background: Many patients with obsessive-compulsive disorder do not respond adequately to serotonin reuptake inhibitors. Augmentation with antipsychotic drugs can be beneficial in this regard. However, since new relevant randomized controlled trials evaluating new antipsychotics were conducted, a recalculation of the effect sizes appears necessary. Methods: We meta-analyzed all double-blind, randomized, placebo-controlled trials comparing augmentation of serotonin reuptake inhibitors with antipsychotics to placebo supplementation in treatment-resistant obsessive-compulsive disorder. The primary outcome was mean change in the Yale-Brown Obsessive–Compulsive Scale total score. Secondary outcomes were obsessions, compulsions, response rates, and attrition rates. The data collection process was conducted independently by 2 authors. Hedges’s g and risks ratios were calculated as effect sizes. In preplanned meta-regressions, subgroup analyses, and sensitivity analyses, we examined the robustness of the results and explored reasons for potential heterogeneity. Results: Altogether, 14 double-blind, randomized, placebo-controlled trials (n=491) investigating quetiapine (N=4, n=142), risperidone (N=4, n=132), aripiprazole (N=2, n=79), olanzapine (N=2, n=70), paliperidone (N=1, n=34), and haloperidol (N=1, n=34) were incorporated. Augmentation with antipsychotics was significantly more efficacious than placebo in Yale-Brown Obsessive–Compulsive Scale total reduction (N=14, n=478; Hedges’s g=-0.64, 95% CI: -0.87 to -0.41; P=<.01). Aripiprazole (Hedges’s g=-1.35), haloperidol (Hedges’s g=-0.82), and risperidone (Hedges’s g=-0.59) significantly outperformed placebo. Antipsychotics were superior to placebo in treating obsessions, compulsions, and achieving response. There was no between-group difference concerning all-cause discontinuation. The nonsignificant meta-regressions suggest no influence of the antipsychotic dose or baseline symptom severity on the meta

  10. The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study

    PubMed Central

    Ahmed, Mansoor; Aamir, Rozina; Jishi, Zahra; Scharf, Martin B.

    2016-01-01

    Objective: This study examined the effects of milnacipran on polysomnographic (PSG) measures of sleep and subjective complaints in patients with fibromyalgia and disturbed sleep. Methods: This was a single-site, double-blind, placebo-controlled, two-period crossover PSG study. Eligible subjects (aged 28–72 y) were randomized (1:1) to milnacipran (100 mg/d) or placebo for crossover period 1, and vice versa for period 2. Each crossover period comprised a dose-escalation and dose-maintenance phase, with a 2-w taper/washout between periods. In-laboratory PSGs were collected at baseline, and at the end of each treatment period. The primary endpoints were the difference in PSG-recorded wake after sleep onset (WASO), number of awakenings after sleep onset (NAASO), and sleep efficiency (SE) between 4 w of maintenance treatment with milnacipran and placebo. Other PSG measures, subject-rated sleep, fatigue, physical functioning, and pain were assessed. Post hoc analysis was performed in subjects showing at least 25% reduction in pain from baseline in the Brief Pain Inventory Score (responders). Results: Of 19 subjects randomized, 15 completed both periods. Subjects treated with milnacipran showed no significant improvements in WASO and NAASO, but showed reduced SE (p = 0.049). Milnacipran did not show significant improvement in other PSG parameters or subjective endpoints. Two thirds of completers met responder criteria and additionally showed a significant improvement in daily effect of pain (p = 0.043) and subjective sleep quality (p = 0.040). Conclusion: The data suggest that milnacipran is not sedating in most patients with fibromyalgia and improvements in sleep are likely a result of pain improvement. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01234675 Citation: Ahmed M, Aamir R, Jishi Z, Scharf MB. The effects of milnacipran on sleep disturbance in fibromyalgia: a randomized, double-blind, placebo-controlled, two-way crossover study. J Clin Sleep

  11. Escitalopram treatment of depression in human immunodeficiency virus/acquired immunodeficiency syndrome: a randomized, double-blind, placebo-controlled study.

    PubMed

    Hoare, Jacqueline; Carey, Paul; Joska, John A; Carrara, Henri; Sorsdahl, Katherine; Stein, Dan J

    2014-02-01

    Depression can be a chronic and impairing illness in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Large randomized studies of newer selective serotonin reuptake inhibitors such as escitalopram in the treatment of depression in HIV, examining comparative treatment efficacy and safety, have yet to be done in HIV-positive patients. This was a fixed-dose, placebo-controlled, randomized, double-blind study to investigate the efficacy of escitalopram in HIV-seropositive subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, major depressive disorder. One hundred two participants were randomly assigned to either 10 mg of escitalopram or placebo for 6 weeks. An analysis of covariance of the completers found that there was no advantage for escitalopram over placebo on the Montgomery-Asberg Depression Rating Scale (p = 0.93). Sixty-two percent responded to escitalopram and 59% responded to placebo on the Clinical Global Impression Scale. Given the relatively high placebo response, future trials in this area need to be selective in participant recruitment and to be adequately powered.

  12. Comparison of the analgesic efficacy of oral ketorolac versus intramuscular tramadol after third molar surgery: A parallel, double-blind, randomized, placebo-controlled clinical trial

    PubMed Central

    Isiordia-Espinoza, Mario-Alberto; Martinez-Rider, Ricardo; Perez-Urizar, Jose

    2016-01-01

    Background Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery. Material and Methods A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo (1 mL saline solution); or Group B, oral placebo (similar tablet to oral ketorolac) plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects. Results Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol. Conclusions According to the VAS and AUC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery. Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. PMID:27475688

  13. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

    PubMed Central

    2010-01-01

    Background Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no

  14. Evaluation of the effect of Vaccinium arctostaphylos L. fruit extract on serum inflammatory biomarkers in adult hyperlipidemic patients: a randomized double-blind placebo-controlled clinical trial

    PubMed Central

    Asgary, Sedigheh; Soltani, Rasool; Mirvakili, Saeide; Sarrafzadegan, Nizal

    2016-01-01

    Atherosclerosis is a chronic inflammatory condition. Many pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) are expressed in atherosclerotic lesions. The plants of genus Vaccinium are rich in anthocyanins with anti-inflammatory effects. This study aimed to evaluate the effects of Vaccinium arctostaphylos fruit extract on the serum level of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult patients with mild hyperlipidemia to detect its possible inhibitory effects on progression of atherosclerosis. In a randomized double-blind placebo-controlled clinical trial, eligible hyperlipidemic patients were randomly and equally divided in to two groups of study drug or placebo control to receive either the Vaccinium extract or placebo capsules, respectively, twice daily for four consecutive weeks. Each drug capsule contained 0.8 mg of anthocyanins. Serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 were measured before and after the interventions and finally were compared.A total of 8 men and 12 women in drug group as well as 11 men and 9 women in placebo group completed the study (P = 0.527). The use of Vaccinium extract significantly reduced only the IL-6 level (P = 0.037); however, this reduction was not significant compared to placebo (P = 0.062). Consumption of Vaccinium arctostaphylos fruit extract with the dose of 500 mg twice daily did not show any significant effect on serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult hyperlipidemic patients. However, considering slight decrease in the level of IL-6, ICAM-1, and VCAM-1, the use of higher doses with longer duration might have significant effects on these factors. PMID:27651815

  15. Evaluation of the effect of Vaccinium arctostaphylos L. fruit extract on serum inflammatory biomarkers in adult hyperlipidemic patients: a randomized double-blind placebo-controlled clinical trial.

    PubMed

    Asgary, Sedigheh; Soltani, Rasool; Mirvakili, Saeide; Sarrafzadegan, Nizal

    2016-07-01

    Atherosclerosis is a chronic inflammatory condition. Many pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) are expressed in atherosclerotic lesions. The plants of genus Vaccinium are rich in anthocyanins with anti-inflammatory effects. This study aimed to evaluate the effects of Vaccinium arctostaphylos fruit extract on the serum level of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult patients with mild hyperlipidemia to detect its possible inhibitory effects on progression of atherosclerosis. In a randomized double-blind placebo-controlled clinical trial, eligible hyperlipidemic patients were randomly and equally divided in to two groups of study drug or placebo control to receive either the Vaccinium extract or placebo capsules, respectively, twice daily for four consecutive weeks. Each drug capsule contained 0.8 mg of anthocyanins. Serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 were measured before and after the interventions and finally were compared.A total of 8 men and 12 women in drug group as well as 11 men and 9 women in placebo group completed the study (P = 0.527). The use of Vaccinium extract significantly reduced only the IL-6 level (P = 0.037); however, this reduction was not significant compared to placebo (P = 0.062). Consumption of Vaccinium arctostaphylos fruit extract with the dose of 500 mg twice daily did not show any significant effect on serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult hyperlipidemic patients. However, considering slight decrease in the level of IL-6, ICAM-1, and VCAM-1, the use of higher doses with longer duration might have significant effects on these factors. PMID:27651815

  16. Evaluation of the effect of Vaccinium arctostaphylos L. fruit extract on serum inflammatory biomarkers in adult hyperlipidemic patients: a randomized double-blind placebo-controlled clinical trial

    PubMed Central

    Asgary, Sedigheh; Soltani, Rasool; Mirvakili, Saeide; Sarrafzadegan, Nizal

    2016-01-01

    Atherosclerosis is a chronic inflammatory condition. Many pro-inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) are expressed in atherosclerotic lesions. The plants of genus Vaccinium are rich in anthocyanins with anti-inflammatory effects. This study aimed to evaluate the effects of Vaccinium arctostaphylos fruit extract on the serum level of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult patients with mild hyperlipidemia to detect its possible inhibitory effects on progression of atherosclerosis. In a randomized double-blind placebo-controlled clinical trial, eligible hyperlipidemic patients were randomly and equally divided in to two groups of study drug or placebo control to receive either the Vaccinium extract or placebo capsules, respectively, twice daily for four consecutive weeks. Each drug capsule contained 0.8 mg of anthocyanins. Serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 were measured before and after the interventions and finally were compared.A total of 8 men and 12 women in drug group as well as 11 men and 9 women in placebo group completed the study (P = 0.527). The use of Vaccinium extract significantly reduced only the IL-6 level (P = 0.037); however, this reduction was not significant compared to placebo (P = 0.062). Consumption of Vaccinium arctostaphylos fruit extract with the dose of 500 mg twice daily did not show any significant effect on serum levels of TNF-α, IL-6, ICAM-1, and VCAM-1 in adult hyperlipidemic patients. However, considering slight decrease in the level of IL-6, ICAM-1, and VCAM-1, the use of higher doses with longer duration might have significant effects on these factors.

  17. Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.

    PubMed

    Shahbazkhani, Bijan; Sadeghi, Amirsaeid; Malekzadeh, Reza; Khatavi, Fatima; Etemadi, Mehrnoosh; Kalantri, Ebrahim; Rostami-Nejad, Mohammad; Rostami, Kamran

    2015-06-05

    Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

  18. Clinical effects of topical antifungal therapy in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial of intranasal fluconazole

    PubMed Central

    Hashemian, Farshad; Hashemian, Farnaz; Molaali, Najmeh; Rouini, Mohammadreza; Roohi, Elnaz; Torabian, Saadat

    2016-01-01

    Several studies have been in favor of fungi as a possible pathogenesis of chronic rhinosinusitis (CRS); however, to date, there is no scientific consensus about the use of antifungal agents in disease management. The aim of the present study was to investigate the efficacy of intranasal fluconazole in improving disease symptoms and objective outcomes of patients with CRS. A randomized, double-blind, placebo-controlled study was conducted on 54 patients who were diagnosed with CRS and had not been responsive to routine medical treatments. They were randomly assigned to receive either fluconazole nasal drop 0.2 % or placebo in addition to the standard regimen for a duration of 8 weeks. Patients' outcomes were evaluated according to Sino-Nasal Outcome Test 20 (SNOT-20), endoscopic scores, and Computed Tomography (CT) scores. No statistically significant difference was found in SNOT-20 (p = 0.201), endoscopic (p = 0.283), and CT scores (p = 0.212) of the patients at baseline and after 8-week course of treatment between drug and placebo group. Similar to many studies, the use of topical antifungal treatment for patients with CRS was not shown to be significantly effective. However, further studies are needed to obtain high levels of consistent evidence in order to arrive at a decision whether antifungal therapy is effective in management of CRS or not. PMID:27065776

  19. Randomized double-blind placebo-controlled trial of powdered Brassica rapa ethanol extract on alteration of body composition and plasma lipid and adipocytokine profiles in overweight subjects.

    PubMed

    Jeon, Seon-Min; Kim, Ji-Eun; Shin, Su-Kyung; Kwon, Eun-Young; Jung, Un Ju; Baek, Nam-In; Lee, Kyung-Tae; Jeong, Tae-Sook; Chung, Hae-Gon; Choi, Myung-Sook

    2013-02-01

    We evaluated the effects of Brassica rapa ethanol extract (BREE) on body composition and plasma lipid profiles through a randomized, double-blind, and placebo-controlled trial in overweight subjects. Fifty-eight overweight participants (age 20-50 years, body mass index23.0-24.9) were randomly assigned to two groups and served BREE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. Body compositions, nutrients intake, plasma lipids, adipocytokines, and hepatotoxicity biomarkers were assessed in all subjects at baseline and after 10 weeks of supplementation. The plasma total cholesterol (total-C) concentration was significantly increased after 10 weeks compared to the baseline in both groups. However, BREE supplementation significantly increased the high-density lipoprotein cholesterol (HDL-C) concentration and significantly reduced the total-C/HDL-C ratio, free fatty acid, and adipsin levels after 10 weeks. No significant differences were observed in body compositions, fasting blood glucose, plasma adipocytokines except adipsin, and aspartate aminotransferase and alanine aminotransferase activities between before and after trial within groups as well as between the two groups. The supplementation of BREE partially improves plasma lipid metabolism in overweight subjects without adverse effects.

  20. Oats in the diet of children with celiac disease: preliminary results of a double-blind, randomized, placebo-controlled multicenter Italian study.

    PubMed

    Gatti, Simona; Caporelli, Nicole; Galeazzi, Tiziana; Francavilla, Ruggiero; Barbato, Maria; Roggero, Paola; Malamisura, Basilio; Iacono, Giuseppe; Budelli, Andrea; Gesuita, Rosaria; Catassi, Carlo; Lionetti, Elena

    2013-11-01

    A gluten-free diet (GFD) is currently the only available treatment for patients with celiac disease (CD). Several clinical trials have demonstrated that most celiac patients can tolerate a medium-high quantity of oats without any negative clinical effects; however, the inclusion of oats in GFD is still a matter of debate. In this study, Italian children with CD were enrolled in a 15-month, randomized, double-blind, placebo-controlled multicenter trial. Participants were randomized in two groups following either A-B treatment (6 months of diet "A", 3 months of standard GFD, 6 months of diet "B"), or B-A treatment (6 months of diet "B", 3 months of standard GFD, 6 months of diet "A"). A and B diets included gluten-free (GF) products (flour, pasta, biscuits, cakes and crisp toasts) with either purified oats or placebo. Clinical data (Gastrointestinal Symptoms Rate Scale [GSRS] score) and intestinal permeability tests (IPT), were measured through the study period. Although the study is still blinded, no significant differences were found in GSRS score or the urinary lactulose/mannitol (L/M) ratio between the two groups after 6 months of treatment. These preliminary results suggest that the addition of non-contaminated oats from selected varieties in the treatment of children with CD does not determine changes in intestinal permeability and gastrointestinal symptoms.

  1. Preventive effects of ulinastatin on complications related to pancreaticoduodenectomy: A Consort-prospective, randomized, double-blind, placebo-controlled trial.

    PubMed

    Zhang, Hao; Tan, Chunlu; Wang, Xing; Kang, Deying; Chen, Yonghua; Xiong, Junjie; Tian, Bole; Li, Kezhou; Hu, Weiming; Chen, Xiaoli; Ke, Nengwen; Li, Ang; Liu, Xubao

    2016-06-01

    Postoperative pancreatic fistula (POPF) is one of the most common major complications after pancreaticoduodenectomy (PD). Ulinastatin is an intrinsic trypsin inhibitor and mainly used to treat acute pancreatitis, chronic recurrent pancreatitis, and acute circulatory failure. The study aims to investigate the efficacy of ulinastatin on pancreatic fistula and other complications after PD. This prospective, randomized, double-blind, placebo-controlled trial was conducted in West China Hospital of Sichuan University from December 2012 to December 2014. A total of 106 consecutive patients undergoing PD were randomly assigned to receive ulinastatin or placebo during and after the surgery for 5 days. Baseline clinical characteristics and outcomes of patients were recorded and analyzed. Ninety-two patients including 42 in the ulinastatin group and 50 in the placebo group were available for outcome assessment. The POPF rates were comparable between ulinastatin group (43%) and placebo group (26%), whereas the severe pancreatic fistula rate (grade B + C) was significantly less in ulinastatin group than that in placebo group (7% vs 24%, P = 0.045). For patients with small pancreatic duct diameter (≤3 mm), ulinastatin could significantly reduce the risk of POPF (P = 0.022). Ulinastatin had protective effects for patients undergoing PD on the prevention of severe postoperative pancreatic fistula.

  2. A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA.

    PubMed

    Hong, Z; Moessler, H; Bornstein, N; Brainin, M; Heiss, W-D

    2009-10-01

    Cerebrolysin has exhibited neuroprotective as well as neurotrophic properties in various animal models of cerebral ischaemia and has shown clinical efficacy and good safety in several small controlled clinical studies in ischaemic stroke. Therefore, a large double-blind placebo-controlled randomized clinical trial was launched in Asia to prove the validity of this treatment strategy. In the more than 50 participating centres patients with acute ischemic hemispheric stroke are randomized within 12 hours of symptoms onset to treatment (30 ml Cerebrolysin diluted in physiologic saline) or placebo (saline) given as intravenous infusion once daily added to standard care for 10 days. The patients are followed with regular visits for 90 days. Efficacy is evaluated on day 90 by three outcome scales - modified Rankin Scale, Barthel Index and NIH Stroke Scale - combined to single global directional test. Additionally, adverse events are documented to prove safety. In this study a total of 1060 patients will be included and analysis of data will be completed in 2010. If positive, this trial will add an effective strategy to the treatment of acute ischaemic stroke.

  3. A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Duliang Soft Capsule in Patients with Chronic Daily Headache

    PubMed Central

    Yu, Shengyuan; Hu, Yueqing; Wan, Qi; Zhou, Jiying; Liu, Xinfeng; Qiao, Xiangyang; Yang, Xiaosu; Feng, Jiachun; Chen, Kangning; Pan, Xiaoping; Yang, Qingwu; Dou, Linsen; Liu, Ming; Chen, Yangmei; Yu, Tingmin; Yu, Juming; Li, Zhiwei; Bai, Xue; Duan, Jingfeng

    2015-01-01

    Objective. To investigate the efficacy and safety of traditional Chinese medicine Duliang soft capsule (DSC) in prophylactic treatment for patients with chronic daily headache (CDH). Methods. A multicenter, double-blind, randomized, placebo-controlled clinical study was conducted at 18 Chinese clinical centers. The participants received either DSC or placebo for 4 weeks. The primary efficacy measure was headache-free rate (HFR) in a 4-week period between the pretreatment and posttreatment stages. The secondary efficacy measures were the decrease of headache days, the duration of headache attacks, the frequency of analgesic usage, quality of life, disability, and the headache severity (VAS scores). The accompanying symptoms and adverse events were also assessed. Results. Of 584 CDH patients assessed, 468 eligible patients were randomized. 338 patients received DSC, while 111 patients were assigned in the placebo group. Following treatment, there was a 16.56% difference in HFR favoring DSC over placebo (P < 0.01). Significant differences were also observed between DSC and placebo groups in the secondary measures. However, no statistical difference was found between the two groups in the associated symptoms. No severe adverse effects were observed in the study. Conclusions. DSC might be an effective and well-tolerated option for the prophylactic treatment of patients with CDH. PMID:26101536

  4. A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

    SciTech Connect

    Lips, Irene M.; Gils, Carla H. van; Kotte, Alexis N.T.J.; Leerdam, Monique E. van; Franken, Stefan P.G.; Heide, Uulke A. van der; Vulpen, Marco van

    2012-06-01

    Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

  5. Effect of a Growing-up Milk Containing Synbiotics on Immune Function and Growth in Children: A Cluster Randomized, Multicenter, Double-blind, Placebo Controlled Study

    PubMed Central

    Xuan, Ninh Nguyen; Wang, Dantong; Grathwohl, Dominik; Lan, Phuong Nguyen Thi; Kim, Hoa Vu Thi; Goyer, Amélie; Benyacoub, Jalil

    2013-01-01

    Common infectious diseases, such as diarrhea, are still the major cause of death in children under 5-years-old, particularly in developing countries. It is known that there is a close relationship between nutrition and immune function. To evaluate the effect of a growing-up milk containing synbiotics on immune function and child growth, we conducted a cluster randomized, multicenter, double-blind, placebo controlled clinical trial in children between 18 and 36 months of age in Vietnam. Eligible children from eight and seven kindergartens were randomly assigned to receive test and isocaloric/ isoproteic control milk, respectively, for 5 months. We found that the blood immunoglobulin A (IgA) level and growth parameters were increased in the test group. Compared to the control group, there was also a trend of decreased vitamin A deficiency and fewer adverse events in the test group. These data suggest that a growing-up milk containing synbiotics may be useful in supporting immune function and promoting growth in children. PMID:24353451

  6. Double-blind, randomized, placebo-controlled study of three-month treatment with the combination of ofloxacin and roxithromycin in recent-onset reactive arthritis.

    PubMed

    Kuuliala, Antti; Julkunen, Heikki; Paimela, Leena; Peltomaa, Ritva; Kautiainen, Hannu; Repo, Heikki; Leirisalo-Repo, Marjatta

    2013-11-01

    In a randomized, double-blind, placebo-controlled trial, 56 patients with recent-onset ReA [enteroarthritis, n = 47 (84%); uroarthritis, n = 9 (16%)] were randomly assigned to receive 200 mg ofloxacin and 150 mg roxithromycin twice daily (Combi, n = 26) or placebo (n = 30) for 3 months. Patients were assessed at entry, at 2 weeks, and at 1, 2, 3, 4, 5, and 6 months. The primary outcome measure was recovery from arthritis at 6 months, and secondary outcome measures were swollen and tender joint counts, Ritchie index, serum CRP level, erythrocyte sedimentation rate, and joint pain on a visual analogue scale at 6 months. After 6 months, 20 patients [77% (95% CI 56-91)] in Combi and 20 patients [67% (95% CI 47-83)] in placebo group had recovered from arthritis (p = 0.55), and all clinical and laboratory variables showed improvement with no statistically significant difference between groups. Adverse events were reported by 62% of the patients in the Combi versus 40% in the placebo group. In conclusion, outcome of ReA was good in both treatment groups. Three-month treatment with the combination of ofloxacin and roxithromycin had no advantage over placebo in patients with recent-onset ReA.

  7. Prevention of poststroke depression with milnacipran in patients with acute ischemic stroke: a double-blind randomized placebo-controlled trial.

    PubMed

    Tsai, Ching-Shu; Wu, Chen-Long; Chou, Shih-Yong; Tsang, Hin-Yeung; Hung, Tai-Hsin; Su, Jian-An

    2011-09-01

    Poststroke depression (PSD) is one of the most frequent neuropsychiatric consequences of stroke. It has been shown to be associated with both impaired recovery and increased mortality. The purpose of this study is to investigate the prophylactic effect of milnacipran in PSD. Ninety-two patients were enrolled in the 12 months of this double-blind randomized placebo-controlled trial. The assessment was performed at baseline, and at the first, third, sixth, ninth and 12th month after enrollment. The definition of PSD was in accordance with the diagnostic criteria of major depressive episode based on the Diagnostic and Statistical Manual, fourth edition. Forty-six patients were randomized to the treatment group with milnacipran and another 46 patients to the placebo group. No significant differences were found between the two groups in terms of sex (P=0.83), age (P=0.08), marital status (P=0.66), occupation (P=0.22), educational level (P=0.29), and drug side-effects (P=0.73). The incidence of depression in the two groups was 2.22% and 15.22%, respectively. Milnacipran was proved to have a statistically significant advantage in preventing PSD (P<0.05). In conclusion, milnacipran could prevent the development of depression in the first year following a stroke and is safe to use without significant adverse effects in stroke patients. PMID:21811172

  8. The effect of simvastatin in penile erection: a randomized, double-blind, placebo-controlled clinical trial (Simvastatin treatment for erectile dysfunction-STED TRIAL).

    PubMed

    Mastalir, E T; Carvalhal, G F; Portal, V L

    2011-01-01

    The aim of the study is to evaluate the effect of simvastatin in erectile dysfunction (ED) secondary to endothelial dysfunction. This study is a double-blind, randomized, placebo-controlled, clinical trial in patients with ED and endothelial dysfunction. Patients were randomized to receive 20 mg simvastatin (n = 21) or placebo (n = 20) daily for 6 months and subsequently 10 mg of vardenafil on demand for 4 weeks. Serum cholesterol, hormone profile, ultrasensitive C-reactive protein, the International Index of Erectile Dysfunction (IIEF) and the ED Index of Treatment Satisfaction were evaluated. There was a significant reduction in serum cholesterol in the treatment group. The hormonal profile remained unaltered. There was no difference in the IIEF between the groups at follow-up, although, at the beginning, 26% of the patients of both groups presented with mild ED and 74% with moderate-to-severe ED; at the end of the 7th month, all patients from the simvastatin group progressed to mild ED, compared with only 83% in the placebo group. There was no statistically significant difference in penile erection after intake of simvastatin or placebo. This study does not support the use of simvastatin as erectogenic medication. Further studies are necessary to verify if simvastatin has any beneficial effect on ED.

  9. Effects of a mouthwash containing potassium nitrate, sodium fluoride, and cetylpyridinium chloride on dentin hypersensitivity: a randomized, double-blind, placebo-controlled study

    PubMed Central

    2016-01-01

    Purpose We evaluated the efficacy of a mouthwash containing potassium nitrate (KNO3) as its main component, along with sodium fluoride (NaF) and cetylpyridinium chloride (CPC). The primary endpoint was the relief of dentin hypersensitivity (DH) against the cold stimuli. The effects on other DH tests and periodontal inflammation were also evaluated. Methods We used a single-center, double-blind, placebo-controlled, randomized design. A total of 82 patients with DH (40 in the test group, 42 placebo controls) were analyzed using visual analog scales (VASs) for a cold test, a tactile test, a compressive air test, and self-reported pain during daily activities, as well as clinical parameters including plaque index, gingival index, modified sulcular bleeding index (mSBI), gingival recession, and probing depth, which were collected at baseline and after four and six weeks of mouthwash use. Results VAS scores for cold sensations, tactile sensations, the compressive air test, and self-reported pain significantly decreased from baseline during the six weeks in both groups (P<0.01), and no significant differences between the groups were found. In male patients (10 in the test group and 7 in the control group), both groups showed significant reductions in VAS scores for the cold test over the six weeks, and greater reductions were found in the test group than in the control group between four and six weeks (P=0.01) and between baseline and six weeks (P<0.01). In addition, the mSBI in the test group significantly decreased from baseline during the six weeks (P<0.01), and the changes at four and six weeks from baseline were significantly greater in the test group compared to the control group (P=0.03 and P=0.02, respectively). Conclusions A mouthwash containing a mixture of KNO3, NaF, and CPC reduced DH and gingival inflammation, however, the efficacy was comparable to the control group. PMID:26937293

  10. A Prospective Randomized Double Blind Placebo Controlled Trial on the Efficacy of Ethanol Celiac Plexus Neurolysis in Patients with Operable Pancreatic and Periampullary Adenocarcinoma

    PubMed Central

    Lavu, Harish; Lengel, Harry B; Sell, Naomi M; Baiocco, Joseph A; Kennedy, Eugene P; Yeo, Theresa P; Burrell, Sherry A; Winter, Jordan M; Hegarty, Sarah; Leiby, Benjamin E.; Yeo, Charles J

    2015-01-01

    Background Ethanol celiac plexus neurolysis (ECPN) has been shown to be effective in reducing cancer-related pain in patients with locally advanced pancreatic and periampullary adenocarcinoma (PPA). This study examined its efficacy in patients undergoing PPA resection. Study Design 485 patients participated in this prospective, randomized, double blind placebo controlled trial. Patients were stratified by preoperative pain and disease resectability. They received either ECPN (50% ethanol) or 0.9% normal saline placebo control. The primary endpoint was short and long-term pain and secondary endpoints included postoperative morbidity, QOL and overall survival. Results Data from 467 patients were analyzed. The primary endpoint, the percentage of PPA patients experiencing a worsening of pain compared to preoperative baseline for resectable patients, was not different between the ethanol and saline groups in either the resectable/pain stratum (22% vs 18%, RR 1.23 (0.34, 4.46)), or the resectable/no pain stratum (37% vs 34%, RR 1.10 (0.67, 1.81)). On multivariable analysis of resected pancreatic ductal adenocarcinoma (PDA) patients, there was a significant reduction in pain in the resectable/pain group, suggesting that surgical resection of the malignancy alone (independent of ECPN) decrements pain to a significant degree. Conclusions In this study, we have demonstrated a significant reduction in pain following surgical resection of PPA. However the addition of ECPN did not synergize to result in a further reduction in pain, and in fact its effect may have been masked by surgical resection. Given this, we cannot recommend the use of ECPN to mitigate cancer related pain in resectable PPA patients. PMID:25667135

  11. Nitroglycerin 0.4% ointment vs placebo in the treatment of pain resulting from chronic anal fissure: a randomized, double-blind, placebo-controlled study

    PubMed Central

    2013-01-01

    Background Complications of chronic anal fissure (CAF) treatments are prompting interest in lower-risk therapies. This study was conducted to compare nitroglycerin (NTG) 0.4% ointment with placebo for pain associated with CAF. Methods In this randomized, double-blind, placebo-controlled trial, patients with one CAF and moderate-to-severe pain (≥50 mm on a 100 mm visual analog scale [VAS]) received 375 mg NTG 0.4% (1.5 mg active ingredient) or 375 mg placebo ointment applied anally every 12 hours for 21 days. The primary end point was change from baseline VAS score in 24-hour pain averaged over days 14–18. Review of data from patients who withdrew early was blinded to treatment. To control for the confounding effects of analgesics, all patients received 650 mg acetaminophen for headache prophylaxis before each application. Results A total of 247 patients were enrolled (NTG, n = 123; placebo, n = 124). The prespecified baseline observation carried forward (BOCF) analysis found no significant difference between groups; however, a last observation carried forward (LOCF) analysis showed a significant advantage for NTG. A post hoc analysis (LOCF/BOCF hybrid) demonstrated a significant adjusted mean difference of −7.0 mm in favor of NTG 0.4% (95% CI −13.6, –0.4; P = .038). Headache was the most common adverse event in the NTG (69.9%) and placebo (47.6%) groups. Conclusions This was the first placebo-controlled study that also controlled for the confounding effects of analgesics used to treat NTG-induced headache. In patients with moderate-to-severe CAF pain, NTG 0.4% ointment effectively reduced CAF pain compared with placebo. Trial registration ClinicalTrials.gov, NCT00522041 PMID:23815124

  12. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

    PubMed

    Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

    1998-08-01

    Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to

  13. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

    PubMed

    Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

    1998-08-01

    Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p < 0.001, p < 0.001, p = 0.017, respectively) from placebo but the fluvoxamine group did not (p = 0.38). Compared with baseline, paroxetine exerted the strongest delay in ejaculation, followed by fluoxetine and sertraline. There was no clinically relevant delay in ejaculation with fluvoxamine. In men with lifelong rapid ejaculation, paroxetine delayed ejaculation most strongly, whereas fluvoxamine delayed ejaculation the least. The second double-blind, placebo-controlled study was carried out in men with lifelong rapid ejaculation (IELT < or = 1 minute) and in men with lifelong less-rapid ejaculation (IELT > 1 minute) to

  14. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Tiralongo, Evelin; Wee, Shirley S.; Lea, Rodney A.

    2016-01-01

    Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry’s physical and mental health benefits. PMID:27023596

  15. The effect of desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder: a substudy of a randomized, double-blind, placebo-controlled trial.

    PubMed

    Reddy, Sujana; Fayyad, Rana; Edgar, Chris J; Guico-Pabia, Christine J; Wesnes, Keith

    2016-06-01

    The objective of this substudy was to examine the effect of desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for desvenlafaxine (-226.6 msec (-316.7, -136.4); P<0.0001) and for placebo (-133.3 msec (-257.2, -9.4); P=0.0354); however, the treatment effect was not significant. No significant differences between groups were observed on composite measures for attention. Treatment of depression with desvenlafaxine 50 mg/day may improve aspects of cognitive functioning, including working memory.Clinical Trial Registry No.: Clinicaltrials.gov identifier: NCT00824291.

  16. Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Liu, Guosong; Weinger, Jason G.; Lu, Zhong-Lin; Xue, Feng; Sadeghpour, Safa

    2015-01-01

    Background: Cognitive impairment is a major problem in elderly, affecting quality of life. Pre-clinical studies show that MMFS-01, a synapse density enhancer, is effective at reversing cognitive decline in aging rodents. Objective: Since brain atrophy during aging is strongly associated with both cognitive decline and sleep disorder, we evaluated the efficacy of MMFS-01 in its ability to reverse cognitive impairment and improve sleep. Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-designed trial in older adult subjects (age 50–70) with cognitive impairment. Subjects were treated with MMFS-01 (n = 23) or placebo (n = 21) for 12 weeks and cognitive ability, sleep quality, and emotion were evaluated. Overall cognitive ability was determined by a composite score of tests in four major cognitive domains. Results: With MMFS-01 treatment, overall cognitive ability improved significantly relative to placebo (p = 0.003; Cohen’s d = 0.91). Cognitive fluctuation was also reduced. The study population had more severe executive function deficits than age-matched controls from normative data and MMFS-01 treatment nearly restored their impaired executive function, demonstrating that MMFS-01 may be clinically significant. Due to the strong placebo effects on sleep and anxiety, the effects of MMFS-01 on sleep and anxiety could not be determined. Conclusions: The current study demonstrates the potential of MMFS-01 for treating cognitive impairment in older adults. PMID:26519439

  17. The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Zhu, Jingfen; Shi, Rong; Chen, Su; Dai, Lihua; Shen, Tian; Feng, Yi; Gu, Pingping; Shariff, Mina; Nguyen, Tuong; Ye, Yeats; Rao, Jianyu; Xing, Guoqiang

    2016-01-01

    Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47–88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs. PMID:27190539

  18. Efficacy of Chinese Herbal Medicine for Diarrhea-Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

    PubMed Central

    Liu, Shan; Su, Xiao-Lan; Wang, Zi-Song; Li, Yi-Jie; Yang, Yang; Hou, Li-Wei; Wang, Qing-Guo; Wei, Ru-Han; Yang, Jian-Qin

    2016-01-01

    Objective. To explore the efficacy of Chinese herbal medicine in treating diarrhea-predominant irritable bowel syndrome (D-IBS). Methods. Four English and four Chinese databases were searched through November, 2015. Randomized, double-blind and placebo-controlled trials were selected. Data extraction and quality evaluation were performed by two authors independently. RevMan 5.2.0 software was applied to analyze the data of included trials. Results. A total of 14 trials involving 1551 patients were included. Meta-analysis demonstrated superior global symptom improvement (RR = 1.62; 95% CI 1.31, 2.00; P < 0.00001; number needed to treat = 3.6), abdominal pain improvement (RR = 1.95; 95% CI 1.61, 2.35; P < 0.00001), diarrhea improvement (RR = 1.87; 95% CI 1.60, 2.20; P < 0.00001), pain threshold assessment (MD = 54.53; 95% CI 38.76, 70.30; P < 0.00001), and lower IBS Symptom Severity Score (SMD = −1.01; 95% CI −1.72, −0.30; P = 0.005), when compared with placebo, while for defecation threshold assessment, quality of life, and adverse events, no differences were found between treatment groups and controlled groups. Conclusion. This meta-analysis shows that Chinese herbal medicine is an effective and safe treatment for D-IBS. However, due to the small sample size and high heterogeneity, further studies are required. PMID:27547226

  19. A Double Blind, Randomized, Placebo Controlled Clinical Study Evaluates the Early Efficacy of Aflapin® in Subjects with Osteoarthritis of Knee

    PubMed Central

    Vishal, Amar A.; Mishra, Artatrana; Raychaudhuri, Siba P

    2011-01-01

    Aflapin® is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is more efficacious as an anti-inflammatory agent compared to the existing Boswellia products, 5-Loxin® and traditional 65% Boswellia extract. A 30-day, double-blind, randomized, placebo-controlled study was conducted to validate the efficacy of Aflapin® in the management of clinical symptoms of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN69643551). Sixty eligible OA subjects selected through screening were included in the study. The subjects received either 100 mg (n=30) of Aflapin® or placebo (n=30) daily for 30 days. Each subject was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 5, 15 and 30. A series of biochemical tests in serum, urine and hematological parameters established the safety of Aflapin. The observations suggest that Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Aflapin provided significant improvements in pain score and functional ability in as early as 5 days of treatment. In conclusion, our observations suggest that Aflapin is a safe, fast acting and effective alternative intervention in the management of OA. PMID:22022214

  20. Antihelminthic Therapy and Antimony in Cutaneous Leishmaniasis: A Randomized, Double-Blind, Placebo-Controlled Trial in Patients Co-Infected with Helminths and Leishmania braziliensis

    PubMed Central

    Newlove, Tracey; Guimarães, Luiz H.; Morgan, Daniel J.; Alcântara, Leda; Glesby, Marshall J.; Carvalho, Edgar M.; Machado, Paulo R.

    2011-01-01

    Helminth infections influence the clinical response to certain diseases and are associated with delayed healing time of patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. We conducted a randomized, double-blind, placebo-controlled clinical trial to examine the role of early versus deferred treatment of intestinal helminth infection on the clinical course of patients with CL treated with pentavalent antimony. (Clinicaltrials.gov number NCT00469495). A total of 90 patients were enrolled, 51.1% (N = 23) of control patients had persistent lesions at Day 90, compared with 62.2% (N = 28) in the treatment group (difference 11.1%, 95% confidence interval = −9.1–30.0%). There was no statistically significant difference in overall time to cure between groups, although there was a tendency for shorter cure times in the control group. This study shows that early introduction of antihelminthic therapy does not improve clinical outcome in patients co-infected with helminths and L. braziliensis. PMID:21460008

  1. Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

    2015-05-27

    Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

  2. Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study

    PubMed Central

    McCleane, Gary

    2000-01-01

    Aims To assess the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin and a combination of 3.3% doxepin and 0.025% capsaicin in human chronic neuropathic pain. Methods A randomized, double-blind, placebo-controlled study of 200 consenting adult patients. Patients applied placebo, doxepin, capsaicin or doxepin/capsaicin cream daily for 4 weeks. Patients recorded on a daily basis overall pain, shooting, burning, paraesthesia and numbness using a 0–10 visual analogue scale during the week prior to cream application (baseline levels) and for the 4 week study period. Side-effects and desire to continue treatment were also recorded. Results Overall pain was significantly reduced by doxepin, capsaicin and doxepin/capsaicin to a similar extent. The analgesia with doxepin/capsaicin was of more rapid onset. Capsaicin significantly reduced sensitivity and shooting pain. Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin. Side-effects were minor. One patient requested to continue placebo cream, 17 doxepin cream, 13 capsaicin and 9 the combination of doxepin and capsaicin. Conclusions Topical application of 3.3% doxepin, 0.025% capsaicin and 3.3% doxepin/0.025% capsaicin produces analgesia of similar magnitude. The combination produces more rapid analgesia. PMID:10848721

  3. Myoinositol/folic acid combination for the treatment of erectile dysfunction in type 2 diabetes men: a double-blind, randomized, placebo-controlled study.

    PubMed

    Agostini, R; Rossi, F; Pajalich, R

    2006-01-01

    Erectile dysfunction is a common complication of diabetes. Diabetes can cause neuropathy or damage to nerves throughout your body, including the penis. Damaged nerves can't communicate properly. So even though you might be emotionally stimulated to have intercourse, nerve damage means that information isn't relayed to the penis, and it doesn't respond. In addition, poor blood sugar control can inhibit nitric oxide production. Lack of nitric oxide can prevent the pressure of blood in the corpora cavernosa from rising enough to close off penile veins, allowing blood to flow out of the penis instead of remaining trapped for an erection. This prospective, randomized, double-blind, placebo-controlled study included 176 patients with type 2 diabetes. The daily 4 g dose of inositol plus 400 microg of folic acid or placebo was divided and given in three doses. The present study demonstrates that Myoinositol/folic acid combination, deserves consideration as therapeutic agent for preventing and treating erectile dysfunction in diabetic men, probably by virtue of both their chronic metabolic, acute ROS scavenging, and NO protective beneficial effects.

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

    PubMed

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

    2012-09-15

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

  5. Effect of nitrate supplementation on hepatic blood flow and glucose homeostasis: a double-blind, placebo-controlled, randomized control trial.

    PubMed

    Shepherd, Anthony I; Wilkerson, Daryl P; Fulford, Jon; Winyard, Paul G; Benjamin, Nigel; Shore, Angela C; Gilchrist, Mark

    2016-09-01

    Nitric oxide alters gastric blood flow, improves vascular function, and mediates glucose uptake within the intestines and skeletal muscle. Dietary nitrate, acting as a source of nitric oxide, appears to be a potential low-cost therapy that may help maintain glucose homeostasis. In a randomized, double-blind, placebo-controlled crossover study, 31 young and older adult participants had a standardized breakfast, supplemented with either nitrate-rich beetroot juice (11.91 mmol nitrate) or nitrate-depleted beetroot juice as placebo (0.01 mmol nitrate). MRI was used to assess apparent diffusion coefficient (ADC), portal vein flux, and velocity. Plasma glucose, incretin, and C-peptide concentrations and blood pressure were assessed. Outcome variables were measured at baseline and hourly for 3 h. Compared with a placebo, beetroot juice resulted in a significant elevation in plasma nitrate and plasma nitrite concentration. No differences were seen for the young or older adult cohorts between placebo and beetroot juice for ADC, or portal vein flux. There was an interaction effect in the young adults between visits for portal vein velocity. Nitrate supplementation did not reduce plasma glucose, active GLP-1, total GLP-1, or plasma C-peptide concentrations for the young or older adult cohorts. Despite a significant elevation in plasma nitrite concentration following an acute dose of (11.91 mmol) nitrate, there was no effect on hepatic blood flow, plasma glucose, C-peptide, or incretin concentration in healthy adults. PMID:27418682

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

    PubMed

    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. Placebo controlled, prospectively randomized, double-blinded study for the investigation of the effectiveness and safety of the acoustic wave therapy (AWT(®)) for cellulite treatment.

    PubMed

    Russe-Wilflingseder, Katharina; Russe-Wilfingsleder, Katharina; Russe, Elisabeth; Vester, Johannes C; Haller, Gerd; Novak, Pavel; Krotz, Alexander

    2013-06-01

    Placebo controlled double-blinded, prospectively randomized clinical trial with 17 patients (11 verum, 5 placebo) for evaluation of cellulite treatment with Acoustic Wave Therapy, (AWT(®)) was performed. The patients were treated once a week for 7 weeks, a total of 8 treatments with the D-ACTOR(®) 200 by Storz Medical AG. Data were collected at baseline, before 8th treatment, at 1 month (follow-up 1) and at 3 months (follow-up 2) after the last treatment with a patients' questionnaire, weight control, measurement of circumference and standardized photography. Treatment progress was further documented using a specially designed 3D imaging system (SkinSCAN(3D), 3D-Shape GmbH) providing an objective measure of cellulite (primary efficacy criteria). Patient's questionnaire in the verum group revealed an improvement in number and depth of dimples, skin firmness and texture, in shape and in reduction of circumference. The overall result (of skin waviness, Sq and Sz, surface and volume of depressions and elevations, Vvv and Vmp) at two follow-up visits indicates a more than medium sized superiority (MW = 0.6706) and is statistically significant (pWei-Lachin = 0.0106). The placebo group revealed no statistical significance. No side effects were seen. This indicates the efficacy and safety of AWT(®) for patients with cellulite.

  8. N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Moslehi, A; Taghizadeh-Ghehi, M; Gholami, K; Hadjibabaie, M; Jahangard-Rafsanjani, Z; Sarayani, A; Javadi, M; Esfandbod, M; Ghavamzadeh, A

    2014-06-01

    Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) which is frequently observed in hematopoietic SCT settings. Antioxidant agents have been proposed to prevent OM and therefore N-acetyl cysteine (NAC) could have an important role. In the present study, we conducted a double-blind, randomized, placebo-controlled study to evaluate the NAC effect on OM incidence and severity, and also glutathione peroxidase-1 activity. Leukemia patients undergoing allogeneic hematopoietic SCT preceded by HDC were recruited into the study and received either NAC (100 mg/kg/day) (n=38) or placebo (n=42) from the starting day of HDC until day +15 after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the NAC group (23.7% vs 45.3%, P=0.04). Moreover, the mean duration of OM was significantly shorter in the intervention group (6.24(2.96) vs 8.12(3.97) days, P=0.02). The glutathione peroxidase-1 activity was also significantly higher in the NAC group seven days after transplantation (3.38(2.19) vs 2.41(1.70) ng/mL, P=0.003). It is concluded that parenteral NAC is effective in reducing the incidence of severe cases and the total duration of OM. PMID:24614837

  9. Effects Of Recombinant Human Erythropoietin On Platelet Activation In Acute Myocardial Infarction: Results Of A Double-Blind, Placebo-Controlled Randomized Trial

    PubMed Central

    Tang, Yi-Da; Hasan, Faisal; Giordano, Frank J.; Pfau, Stephen; Rinder, Henry M.; Katz, Stuart D.

    2009-01-01

    Background Erythropoietin mitigates myocardial damage and improves ventricular performance after experimental ischemic injury. This study assessed safety and efficacy markers relevant to the biological activity of recombinant human erythropoietin (rHuEpo) in patients with acute myocardial infarction. Methods We conducted a prospective, placebo-controlled, randomized, double-blind trial to determine the effects of intravenous rHuEpo (200 U/kg daily for 3 consecutive days) on measures of platelet and endothelial cell activation, soluble Fas ligand, and peripheral blood mononuclear cell (PBMC) expression of angiogenesis signaling proteins in 44 subjects with acute myocardial infarction (MI) treated with aspirin and clopidogrel after successful percutaneous coronary intervention. Results rHuEpo did not alter bleeding time, platelet function assay closure time, von Willebrand factor levels, soluble P-selectin, or soluble Fas ligand levels when compared with placebo. By contrast, rHuEpo significantly increased expression of erythropoietin receptor, vascular endothelial growth factor receptor Flt-1, and phosphorylated phosphatidylinositol 3-kinase in PBMC’s when compared with placebo (all p<0.05). Conclusions In acute MI patients treated with aspirin and clopidogrel, short-term administration of rHuEpo did not alter markers of platelet and endothelial cell activation associated with thrombosis, yet did increase expression of angiogenesis signaling proteins in PBMC’s when compared with placebo. These data provide preliminary evidence of safety and biologic activity of rHuEpo at this dosing and support continued enrollment in ongoing efficacy trials. PMID:19958860

  10. Sociodemographic and smoking behavioral predictors associated with smoking cessation according to follow-up periods: a randomized, double-blind, placebo-controlled trial of transdermal nicotine patches.

    PubMed

    Myung, Seung Kwon; Seo, Hong Gwan; Park, Sohee; Kim, Yeol; Kim, Dong Jin; Lee, Do Hoon; Seong, Moon Woo; Nam, Myung Hyun; Oh, Seung Won; Kim, Ji Ae; Kim, Mi Young

    2007-12-01

    This study investigated sociodemographic and smoking behavioral factors associated with smoking cessation according to follow-up periods. In this randomized, double-blind, placebo-controlled trial of transdermal nicotine patches, subjects were a total of 118 adult male smokers, who were followed up for 12 months. Univariable logistic regression analysis and stepwise multiple logistic regression analyses were performed to identify the predictors of smoking cessation. The overall self-reported point prevalence rates of abstinence were 20% (24/118) at 12 months follow-up, and there was no significant difference in abstinence rates between placebo and nicotine patch groups. In the univariable logistic regression analysis, predictors of successful smoking cessation were the low consumption of cigarettes per day and the low Fagerstrom Test for Nicotine Dependence (FTND) scores (p<0.05) at 3, 6, and 12 months follow-up. In the stepwise multiple logistic regression analyses, predictors of successful smoking cessation, which were different according to the follow- up periods, were found to be the low consumption of cigarettes per day at the short-term and midterm follow-up (< or =6 months), older age, and the low consumption of cigarettes per day at the long-term follow-up (12 months).

  11. A randomized, double-blind, placebo-controlled trial to assess the bacterial anti-adhesion effects of cranberry extract beverages.

    PubMed

    Kaspar, Kerrie L; Howell, Amy B; Khoo, Christina

    2015-04-01

    In this study, we examined the ex vivo urinary anti-adhesion activity of low-calorie cranberry extract beverages in both a pilot study (n = 10) and a randomized, double-blind, placebo controlled clinical trial (n = 59). In the pilot study, subjects consumed a cranberry extract beverage (CEB) or a cranberry extract and juice beverage (CEJB), compared to placebo. Both cranberry beverages utilized a standardized cranberry extract powder at a level equivalent to low-calorie cranberry juice cocktail (LCJC) on a PAC content basis. Clean-catch urine samples collected at baseline and post intervention were tested for anti-adhesion activity utilizing a mannose-resistant human red blood cell hemagglutination assay specific for P-fimbriated E. coli. Results from the pilot study indicated that ex vivo anti-adhesion activity for both cranberry treatments were higher (p < 0.05) than placebo. In the clinical trial, we compared CEJB to LCJC and a placebo beverage. Post-consumption urine from both cranberry treatment groups showed significantly higher (p < 0.05) anti-adhesion activity compared to placebo. There were no differences observed in anti-adhesion activity between CJEB and LCJC, indicating similar bioactivity. Therefore, acute beverage consumption of cranberry extract and/or juice provides ex vivo anti-adhesion activity, which may help to improve urinary tract health. PMID:25723356

  12. Efficacy of Chinese Herbal Medicine for Diarrhea-Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials.

    PubMed

    Zhu, Jia-Jie; Liu, Shan; Su, Xiao-Lan; Wang, Zi-Song; Guo, Yu; Li, Yi-Jie; Yang, Yang; Hou, Li-Wei; Wang, Qing-Guo; Wei, Ru-Han; Yang, Jian-Qin; Wei, Wei

    2016-01-01

    Objective. To explore the efficacy of Chinese herbal medicine in treating diarrhea-predominant irritable bowel syndrome (D-IBS). Methods. Four English and four Chinese databases were searched through November, 2015. Randomized, double-blind and placebo-controlled trials were selected. Data extraction and quality evaluation were performed by two authors independently. RevMan 5.2.0 software was applied to analyze the data of included trials. Results. A total of 14 trials involving 1551 patients were included. Meta-analysis demonstrated superior global symptom improvement (RR = 1.62; 95% CI 1.31, 2.00; P < 0.00001; number needed to treat = 3.6), abdominal pain improvement (RR = 1.95; 95% CI 1.61, 2.35; P < 0.00001), diarrhea improvement (RR = 1.87; 95% CI 1.60, 2.20; P < 0.00001), pain threshold assessment (MD = 54.53; 95% CI 38.76, 70.30; P < 0.00001), and lower IBS Symptom Severity Score (SMD = -1.01; 95% CI -1.72, -0.30; P = 0.005), when compared with placebo, while for defecation threshold assessment, quality of life, and adverse events, no differences were found between treatment groups and controlled groups. Conclusion. This meta-analysis shows that Chinese herbal medicine is an effective and safe treatment for D-IBS. However, due to the small sample size and high heterogeneity, further studies are required. PMID:27547226

  13. Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Villegas-Rivera, Geannyne; Román-Pintos, Luis Miguel; Cardona-Muñoz, Ernesto Germán; Arias-Carvajal, Oscar; Rodríguez-Carrizalez, Adolfo Daniel; Troyo-Sanromán, Rogelio; Pacheco-Moisés, Fermín Paul; Moreno-Ulloa, Aldo; Miranda-Díaz, Alejandra Guillermina

    2015-01-01

    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. PMID:26290682

  14. A randomized, double-blind, placebo-controlled trial of a Chinese herbal Sophora flower formula in patients with symptomatic haemorrhoids: a preliminary study.

    PubMed

    Man, Kee-Ming; Chen, Wen-Chi; Wang, Hwei-Ming; Chen, Huey-Yi; Shen, Jui-Lung; Chen, Lieh-Der; Tsai, Fuu-Jen; Chen, Yung-Hsiang; Yu, De-Xin; Chiang, Feng-Fan

    2013-01-01

    Dried flowers and buds of Sophora japonica (Huaihua) are used in China, Japan and Korea for treating haematemesis and bleeding haemorrhoids. This study compared the clinical safety and efficacy of a Sophora flower formula with a placebo for the conservative treatment of symptomatic haemorrhoids. The study was a prospective, double-blind, randomized placebo-controlled trial. The clinical effective rate, symptom score and the incidence of important clinical events were used as observation indices to evaluate the effect of the Sophora flower formula. The results showed that after 7 days of treatment, improvement was observed in 87.0% of the patients' major symptoms in the Sophora flower formula group compared with 81.8% of those in the placebo group. After 14 days, 78.2% patients in the Sophora flower formula group were asymptomatic, whereas 40.9% of those in the placebo group exhibited residual symptoms. However, the difference between both groups was not statistically significant. As the bowel habits of the patients improved and as the patients took sitz baths, their symptoms improved drastically, regardless of the use of the Sophora flower formula. These findings indicate that the traditional Chinese Sophora flower formula is clinically safe; however, its effects on haemorrhoids need to be studied in a larger sample size and with different dosages. The present study results may be a potential clinical reference for physicians prescribing medications for patients with symptomatic haemorrhoids. PMID:24146460

  15. Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study

    PubMed Central

    Melnikovova, Ingrid; Fait, Tomas; Kolarova, Michaela; Fernandez, Eloy C.; Milella, Luigi

    2015-01-01

    Background/Aims. Products of Lepidium meyenii Walp. (maca) are touted worldwide as an alimentary supplement to enhance fertility and restore hormonal balance. Enhancing properties of maca on semen parameters in animals were previously reported by various authors, but we present to the best of our knowledge the first double-blind, randomized, placebo-controlled pilot trial in men. The aim of this study was to evaluate the effects of maca on semen parameters and serum hormone levels in healthy adult men. Methods. A group of 20 volunteers aged 20–40 years was supplied by milled hypocotyl of maca or placebo (1.75 g/day) for 12 weeks. Negative controls of semen were compared to the samples after 6 and 12 weeks of maca administration; negative blood controls were compared to the samples after 12 weeks of treatment. Results. Sperm concentration and motility showed rising trends compared to placebo even though levels of hormones did not change significantly after 12 weeks of trial. Conclusion. Our results indicate that maca possesses fertility enhancing properties in men. As long as men prefer to use alimentary supplement to enhance fertility rather than prescribed medication or any medical intervention, it is worth continuing to assess its possible benefits. PMID:26421049

  16. Antihyperlipidemic effects of Salvia officinalis L. leaf extract in patients with hyperlipidemia: a randomized double-blind placebo-controlled clinical trial.

    PubMed

    Kianbakht, S; Abasi, B; Perham, M; Hashem Dabaghian, F

    2011-12-01

    Hyperlipidemia is a common metabolic disorder contributing to morbidities and mortalities due to cardiovascular and cerebrovascular diseases. Conventional antihyperlipidemic drugs have limited efficacies and important side effects, so that alternative lipid lowering agents are needed. Salvia officinalis L. (sage) leaves have PPAR γ agonistic, pancreatic lipase and lipid absorption inhibitory, antioxidant, lipid peroxidation inhibitory and antiinflammatory effects. Thus, in this randomized double-blind placebo-controlled clinical trial with 67 hyperlipidemic (hypercholesterolemic and/or hypertriglyceridemic) patients aged 56.4 ± 30.3 years (mean ± SD), the effects of taking sage leaf extract (one 500 mg capsule every 8 h for 2 months) on fasting blood levels of lipids, creatinine and liver enzymes including SGOT and SGPT were evaluated in 34 patients and compared with the placebo group (n = 33). The extract lowered the blood levels of total cholesterol (p < 0.001), triglyceride (p = 0.001), LDL (p = 0.004) and VLDL (p = 0.001), but increased the blood HDL levels (p < 0.001) without any significant effects on the blood levels of SGOT, SGPT and creatinine (p > 0.05) compared with the placebo group at the endpoint. No adverse effects were reported. The results suggest that sage may be effective and safe in the treatment of hyperlipidemia.

  17. Effect of NR-Salacia on post-prandial hyperglycemia: A randomized double blind, placebo-controlled, crossover study in healthy volunteers

    PubMed Central

    Koteshwar, Pravina; Raveendra, Kadur Ramamurthy; Allan, Joseph Joshua; Goudar, Krishnagouda Shankargouda; Venkateshwarlu, Kudiganti; Agarwal, Amit

    2013-01-01

    Background: Salacia chinensis (S. chinensis) is widely distributed in India and Sri Lanka. Most of the species of genus Salacia are known to have effects on blood glucose levels; however, the effects of S. chinensis on glucose levels are seldom reported. Objective: To evaluate the oral hypoglycemic activity of NR- Salacia (1000 mg extract of S. chinensis) in healthy adults. Materials and Methods: Randomized, double-blind, placebo-controlled, cross-over study was conducted in healthy volunteers. Single dose of NR-Salacia (1000 mg extract of Salacia chinensis) and placebo were administered before carbohydrate-rich diet. A 6-point plasma glucose profile was performed at different time intervals up to 180 min. Results: NR-Salacia treatment significantly lowered plasma glucose level at 90 min, and the percentage reduction in glucose concentration was found to be 13.32 as compared to placebo group. A 33.85% decrease in the plasma glucose positive incremental area under curve (AUC) (0 to 180 min) was observed in comparison to placebo. No adverse events were recorded throughout the study period, except for some mild cases of abdominal discomforts like cramping and distention, vomiting, and headache in both placebo and NR-Salacia-treated groups. Conclusion: The study findings revealed that NR-Salacia lowered the post-prandial plasma glucose levels after a carbohydrate-rich meal and can be used as an oral hypoglycemic agent. PMID:24124287

  18. Effect of onion peel extract supplementation on the lipid profile and antioxidative status of healthy young women: a randomized, placebo-controlled, double-blind, crossover trial.

    PubMed

    Kim, Jungmi; Cha, Yong-Jun; Lee, Kyung-Hea; Park, Eunju

    2013-10-01

    The consumption of fruits and vegetables that have high polyphenol content has been previously associated with a reduced risk for cardiovascular disease. We investigated the effects of onion peel extract on plasma total antioxidant capacity, lipid peroxidation, and leukocyte DNA damage. This study was a randomized, double-blind, placebo-controlled, crossover trial. Healthy female subjects received either onion peel extract or placebo (dextrin) for two weeks, underwent a 1-week washout period, and then received the other treatment for an additional two weeks. After two weeks of onion peel extract supplementation, the total cholesterol level, low-density lipoprotein cholesterol level, and atherogenic index significantly decreased (P < 0.05). No changes were observed in activities of erythrocyte antioxidant enzymes or levels of lipid peroxidation markers following onion peel extract supplementation. Additionally, no significant difference was found in plasma antioxidant vitamin (retinol, tocopherols, carotenoids, and coenzyme Q10) levels or ex vivo H2O2-provoked oxidative DNA damage after onion peel extract supplementation. The present interventional study provides evidence of the health benefits of onion peel extract and demonstrates its effects in modulating lipid profiles in healthy young Korean women. PMID:24133616

  19. Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial

    PubMed Central

    Mazidi, Mohsen; Rokni, Haleh; Sahebkar, Amir Hossein; Mohammadi, Akram; Ghayour-Mobarhan, Majid; Ferns, Gordon A.

    2016-01-01

    Background: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. Methods: Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. Results: Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). Conclusions: Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D. PMID:27330686

  20. A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

    SciTech Connect

    Hille, Andrea . E-mail: ahille@med.uni-goettingen.de; Schmidberger, Heinz; Hermann, Robert M.; Christiansen, Hans; Saile, Bernhard; Pradier, Olivier; Hess, Clemens F.

    2005-12-01

    Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.

  1. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.

    PubMed

    Wade, Derick T; Makela, Petra; Robson, Philip; House, Heather; Bateman, Cynthia

    2004-08-01

    The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild. PMID:15327042

  2. Randomized, double-blind, placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults.

    PubMed

    Valera, Rodrigo; García, Hilda María; Jidy, Manuel Díaz; Mirabal, Mayelin; Armesto, Marlene Isabel; Fando, Rafael; García, Luis; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Ramírez, Margarita; Bravo, Laura; Serrano, Teresita; Palma, Sara; González, Daniel; Miralles, Fernando; Medina, Vilma; Nuñez, Felicita; Plasencia, Yilian; Martínez, Juan Carlos; Mandarioti, Aleyda; Lugones, Juan; Rodríguez, Boris Luis; Moreno, Arlenis; González, Domingo; Baro, Morelia; Solis, Rosa Lidia; Sierra, Gustavo; Barbera, Ramón; Domínguez, Francisco; Gutiérrez, Carlos; Kouri, Gustavo; Campa, Concepción; Menéndez, Jorge

    2009-11-01

    A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.

  3. Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial

    PubMed Central

    Mortazavi, Mehran; Farzin, Davood; Zarhghami, Mehran; Hosseini, Seyed Hamzeh; Mansoori, Parisa; Nateghi, Gholamreza

    2015-01-01

    Background: Zinc can modulate fast-excitatory transmission, facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors. There are also emerging evidences discussing the implication of these neurotransmitters in pathophysiology of schizophrenia. Objectives: The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week, double-blind and placebo-controlled trial. Patients and Methods: Eligible participants were 30 inpatients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Patients were randomly allocated into two equal groups; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate (each containing 50 mg elemental Zn) three times a day and another group received risperidone 6 mg/day plus placebo. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the psychotic symptoms and aggression risk at baseline, week 2, 4, and 6 of the study. Results: The results of this study showed that both protocols significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study. However, this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group. No major clinical side-effects were detected. Conclusions: It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia. PMID:26576178

  4. The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Zhu, Jingfen; Shi, Rong; Chen, Su; Dai, Lihua; Shen, Tian; Feng, Yi; Gu, Pingping; Shariff, Mina; Nguyen, Tuong; Ye, Yeats; Rao, Jianyu; Xing, Guoqiang

    2016-01-01

    Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47-88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs. PMID:27190539

  5. Ananas comosus Effect on Perineal Pain and Wound Healing After Episiotomy: A Randomized Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Golezar, Samira

    2016-01-01

    Background: Ananas comosus has long been used for medical purposes. Currently, we are experiencing an unprecedented interest in the use of complementary medicine as well as a growing attention to traditional products such as bromelain for wound healing and reducing pain. Objectives: The aim of this study was to determine the effect of oral bromelain on perineal pain and wound healing after episiotomy in primiparous women. Patients and Methods: In this double-blind placebo-controlled clinical trial, 82 primiparous women fulfilling the inclusion criteria received bromelain or placebo randomly. Participants were given three tablets, three times a day for six successive days. The initial dose was given 2 hours after delivery. Episiotomy pain was measured using VAS scale before the initial dose, as well as on the 1st hour and on the 3rd, 7th and 14th days after the initial dose. Wound healing was measured using REEDA scale on the 3rd, 7th and 14th days after delivery. Results: Episiotomy pain significantly reduced in bromelain group compared with the placebo group (P < 0.05) and wound healing was faster in bromelain group compared with the placebo group (P < 0.05) on follow-up days. Conclusions: The results showed the effectiveness of bromelain on episiotomy pain and wound healing. Therefore, it is suggested to use bromelain in postoperative stage to improve wound healing and reduce pain. PMID:27247780

  6. Blueberries Improve Endothelial Function, but Not Blood Pressure, in Adults with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Stull, April J.; Cash, Katherine C.; Champagne, Catherine M.; Gupta, Alok K.; Boston, Raymond; Beyl, Robbie A.; Johnson, William D.; Cefalu, William T.

    2015-01-01

    Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus −0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome. PMID:26024297

  7. Improvement of Triglyceride Levels through the Intake of Enriched-β-Conglycinin Soybean (Nanahomare) Revealed in a Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Yuji; Satoh, Hiroki; Takahashi, Yoko; Hajika, Makita; Nishihira, Jun

    2016-01-01

    Soybean is recognized as a beneficial food with various functional components, such as β-conglycinin, which improves lipid metabolism. We evaluated the effects of the β-conglycinin-rich soybean Nanahomare on triglyceride (TG) levels. In this randomized, double-blind, placebo-controlled study, we divided 134 adult subjects into test and placebo groups that consumed processed food containing enriched-β-conglycinin soybean or low-β-conglycinin soybean. Hematological tests and body composition measurements were performed at weeks 0 (baseline), 4, 8, and 12 of the study period. TG levels significantly decreased in the test group compared with the placebo group at weeks 4 (change from baseline to week 4, placebo: 0.27 ± 44.13 mg/dL, test: -20.31 ± 43.74 mg/dL, p = 0.035) and 12 (change from baseline to week 12, placebo: -0.14 ± 65.83 mg/dL, test: -21.30 ± 46.21 mg/dL, p = 0.041). In addition, among subjects whose baseline TG levels were ≥100 mg/dL, the levels significantly improved in the test group at weeks 4 (p = 0.010) and 12 (p = 0.030), whereas the levels were not different between the test and placebo groups among those whose baseline levels were <100 mg/dL. These results suggest that the ingestion of enriched-β-conglycinin soybean improves serum TG levels. PMID:27529274

  8. Effects of polysaccharide derived from black currant on relieving clinical symptoms of Japanese cedar pollinosis: a randomized double-blind, placebo-controlled trial.

    PubMed

    Dejima, Kenji; Ohshima, Akihiro; Yanai, Takaaki; Yamamoto, Reiko; Takata, Ryoji; Yoshikawa, Toshikazu

    2007-12-01

    We investigated the efficacy of the polysaccharide derived from black currant, named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis symptoms and improving quality of life by a randomized double-blind, placebo-controlled trial in 2006. A total of 28 subjects were enrolled in the study, and 10 subjects in each group completed the trial. Although there was no significant difference between the CAPS and placebo group in the weekly mean value of any symptom in the daily symptom diary at any time, a smaller degree of final symptom aggravation was found in the CAPS group. Significant aggravation of the score was finally observed in the placebo group with inferior conch swelling and with sneezing, itchy nose, itchy eye and watery eye in the Japan rhino-conjunctivitis quality of life questionnaire assessment, while the changes observed in the CAPS group were not significant. In conclusion, our findings clearly indicate that CAPS would be useful as a food supplement in assisting the treatment of Japanese cedar pollinosis.

  9. A randomized, double-blind, placebo-controlled study of quetiapine in the treatment of bipolar I and II depression: improvements in quality of life.

    PubMed

    Endicott, Jean; Rajagopalan, Krithika; Minkwitz, Margaret; Macfadden, Wayne

    2007-01-01

    Bipolar depression is associated with significant morbidity, high risk of suicide and substantial impairment of health-related quality of life (QOL), which adversely affects family/social relationships and occupational functioning. Depressive symptomatology is the primary determinant of quality of life, and there is a paucity of clinical trial data on how treatments affect quality of life. This 8-week, randomized, double-blind, parallel-group, placebo-controlled study in 542 patients with bipolar I or II depression used the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire to assess the effect of quetiapine monotherapy, 300 or 600 mg/day, on quality of life. Quality of sleep was also measured using the Pittsburgh Sleep Quality Index. Both doses of quetiapine significantly improved quality of life over baseline values in comparison with placebo, which was evident at first assessment (week 4) and continued up to week 8. The improvement in quality of life was consistent over the majority of the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire domains, and was evident in patients classified as responders on the basis of clinical efficacy measures. Quetiapine therapy also effected a significant improvement in quality of sleep compared with placebo. Improved quality of life may enhance patient compliance, and assessment of quality of life should be incorporated into future clinical trials in bipolar depression.

  10. Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).

    PubMed

    Malerba, Mario; Ponticiello, Antonio; Radaeli, Alessandro; Bensi, Giuliano; Grassi, Vittorio

    2004-01-01

    The objective of this prospective, randomized, double-blind, placebo-controlled, multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria with value of FEV1 between > or =60 and 80% of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo. The percentage of patients free from exacerbation at 6 months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56% with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with more severe baseline symptoms, ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo: 63 vs. 38% (p=0.038). In conclusion, we did not find a significant difference between long-term ambroxol therapy and placebo, in preventing exacerbations in patients with COPD. In patients with more severe respiratory symptoms at baseline, however, we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo, suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD.

  11. A Phase III Randomized, Double Blind, Placebo-Controlled Study of Pilocarpine for Vaginal Dryness: NCCTG study N04CA1

    PubMed Central

    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

    Purpose Vaginal dryness is a common problem, for which effective and safe non-estrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness, the current trial was conducted. Methods 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, to 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 (AUC) summary statistic comprised of the longitudinal responses obtained at baseline and through the six 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-sided alternative to compare the collective pilocarpine treatment arms versus the collective placebo arms. Results 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 to the placebo arm. Conclusion Pilocarpine did not alleviate vaginal dryness. PMID:21702402

  12. Effect of Pumpkin Seed Oil on Hair Growth in Men with Androgenetic Alopecia: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Jeong, Dong Wook; Choi, Eun Jung; Kim, Yun Jin; Lee, Jeong Gyu; Yi, Yu Hyeon; Cha, Hyeong Soo

    2014-01-01

    Pumpkin seed oil (PSO) has been shown to block the action of 5-alpha reductase and to have antiandrogenic effects on rats. This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of PSO for treatment of hair growth in male patients with mild to moderate androgenetic alopecia (AGA). 76 male patients with AGA received 400 mg of PSO per day or a placebo for 24 weeks. Change over time in scalp hair growth was evaluated by four outcomes: assessment of standardized clinical photographs by a blinded investigator; patient self-assessment scores; scalp hair thickness; and scalp hair counts. Reports of adverse events were collected throughout the study. After 24 weeks of treatment, self-rated improvement score and self-rated satisfaction scores in the PSO-treated group were higher than in the placebo group (P = 0.013, 0.003). The PSO-treated group had more hair after treatment than at baseline, compared to the placebo group (P < 0.001). Mean hair count increases of 40% were observed in PSO-treated men at 24 weeks, whereas increases of 10% were observed in placebo-treated men (P < 0.001). Adverse effects were not different in the two groups. PMID:24864154

  13. Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.

    PubMed

    Melnikovova, Ingrid; Fait, Tomas; Kolarova, Michaela; Fernandez, Eloy C; Milella, Luigi

    2015-01-01

    Background/Aims. Products of Lepidium meyenii Walp. (maca) are touted worldwide as an alimentary supplement to enhance fertility and restore hormonal balance. Enhancing properties of maca on semen parameters in animals were previously reported by various authors, but we present to the best of our knowledge the first double-blind, randomized, placebo-controlled pilot trial in men. The aim of this study was to evaluate the effects of maca on semen parameters and serum hormone levels in healthy adult men. Methods. A group of 20 volunteers aged 20-40 years was supplied by milled hypocotyl of maca or placebo (1.75 g/day) for 12 weeks. Negative controls of semen were compared to the samples after 6 and 12 weeks of maca administration; negative blood controls were compared to the samples after 12 weeks of treatment. Results. Sperm concentration and motility showed rising trends compared to placebo even though levels of hormones did not change significantly after 12 weeks of trial. Conclusion. Our results indicate that maca possesses fertility enhancing properties in men. As long as men prefer to use alimentary supplement to enhance fertility rather than prescribed medication or any medical intervention, it is worth continuing to assess its possible benefits. PMID:26421049

  14. Effects of omega-3 fatty acids on tobacco craving in cigarette smokers: A double-blind, randomized, placebo-controlled pilot study.

    PubMed

    Rabinovitz, Sharon

    2014-08-01

    Cigarette smoke induces oxidative stress with subsequent polyunsaturated fatty acids (PUFAs) peroxidation. Low concentrations of omega-3 PUFAs can affect neurotransmission, resulting in hypofunctioning of the mesocortical systems associated with reward and dependence mechanisms and thus may increase cigarette craving, hampering smoking cessation efforts. PUFA deficiency, in particular eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3), has also been linked to reduced psychological health and ability to cope with stress. Although stress is well linked to smoking urges and behavior, no research to date has examined the effects of PUFA supplementation on tobacco craving. In this double-blind, randomized, placebo-controlled pilot study, performed in regular cigarette smokers (n=48), administration of 2710 mg EPA/day and 2040 mg DHA/day for one month was accompanied by a significant decrease in reported daily smoking and in tobacco craving following cigarette cue exposure. Craving did not return to baseline values in the month that followed treatment discontinuation. This is the first study demonstrating that omega-3 PUFA supplementation reduces tobacco craving in regular smokers, compared to placebo treatment. Thus, omega-3 PUFAs may be of benefit in managing tobacco consumption. Further studies are needed on larger samples to explore the possible therapeutic implications for heavy cigarette smokers. PMID:24899596

  15. The Safety and Efficacy of an Enzyme Combination in Managing Knee Osteoarthritis Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Bolten, Wolfgang W.; Glade, Michael J.; Raum, Sonja; Ritz, Barry W.

    2015-01-01

    This randomized, double-blind, placebo-controlled, and comparator-controlled trial evaluated the safety and efficacy of an enzyme combination, as Wobenzym, in adults with moderate-to-severe osteoarthritis (OA) of the knee. Adults (n = 150) received Wobenzym, diclofenac (a nonsteroidal anti-inflammatory drug, NSAID), or placebo for 12 weeks. Improvement in pain scores (Lequesne Functional Index) did not differ between subjects treated with Wobenzym or diclofenac, and both treatment groups improved compared to placebo (P < 0.05). Reduction in total WOMAC scores (secondary outcome measure) did not differ between Wobenzym and diclofenac, although only diclofenac emerged as different from placebo (P < 0.05). The median number of rescue medication (paracetamol) tablets consumed was less in the Wobenzym group compared to placebo (P < 0.05), while there was no difference between diclofenac and placebo. Adverse events were similar in frequency in Wobenzym and placebo groups (7.2% and 9.1% of subjects, resp.) and higher in diclofenac group (15.6%). Wobenzym is comparable to the NSAID diclofenac in relieving pain and increasing function in adults with moderate-to-severe painful knee OA and reduces reliance on analgesic medication. Wobenzym is associated with fewer adverse events and, therefore, may be appropriate for long-term use. PMID:25802756

  16. Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial.

    PubMed

    Tiralongo, Evelin; Wee, Shirley S; Lea, Rodney A

    2016-01-01

    Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry's physical and mental health benefits. PMID:27023596

  17. A randomized, double-blind, placebo-controlled trial of a Chinese herbal Sophora flower formula in patients with symptomatic haemorrhoids: a preliminary study.

    PubMed

    Man, Kee-Ming; Chen, Wen-Chi; Wang, Hwei-Ming; Chen, Huey-Yi; Shen, Jui-Lung; Chen, Lieh-Der; Tsai, Fuu-Jen; Chen, Yung-Hsiang; Yu, De-Xin; Chiang, Feng-Fan

    2013-01-01

    Dried flowers and buds of Sophora japonica (Huaihua) are used in China, Japan and Korea for treating haematemesis and bleeding haemorrhoids. This study compared the clinical safety and efficacy of a Sophora flower formula with a placebo for the conservative treatment of symptomatic haemorrhoids. The study was a prospective, double-blind, randomized placebo-controlled trial. The clinical effective rate, symptom score and the incidence of important clinical events were used as observation indices to evaluate the effect of the Sophora flower formula. The results showed that after 7 days of treatment, improvement was observed in 87.0% of the patients' major symptoms in the Sophora flower formula group compared with 81.8% of those in the placebo group. After 14 days, 78.2% patients in the Sophora flower formula group were asymptomatic, whereas 40.9% of those in the placebo group exhibited residual symptoms. However, the difference between both groups was not statistically significant. As the bowel habits of the patients improved and as the patients took sitz baths, their symptoms improved drastically, regardless of the use of the Sophora flower formula. These findings indicate that the traditional Chinese Sophora flower formula is clinically safe; however, its effects on haemorrhoids need to be studied in a larger sample size and with different dosages. The present study results may be a potential clinical reference for physicians prescribing medications for patients with symptomatic haemorrhoids.

  18. Effects of polysaccharide derived from black currant on relieving clinical symptoms of Japanese cedar pollinosis: a randomized double-blind, placebo-controlled trial.

    PubMed

    Dejima, Kenji; Ohshima, Akihiro; Yanai, Takaaki; Yamamoto, Reiko; Takata, Ryoji; Yoshikawa, Toshikazu

    2007-12-01

    We investigated the efficacy of the polysaccharide derived from black currant, named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis symptoms and improving quality of life by a randomized double-blind, placebo-controlled trial in 2006. A total of 28 subjects were enrolled in the study, and 10 subjects in each group completed the trial. Although there was no significant difference between the CAPS and placebo group in the weekly mean value of any symptom in the daily symptom diary at any time, a smaller degree of final symptom aggravation was found in the CAPS group. Significant aggravation of the score was finally observed in the placebo group with inferior conch swelling and with sneezing, itchy nose, itchy eye and watery eye in the Japan rhino-conjunctivitis quality of life questionnaire assessment, while the changes observed in the CAPS group were not significant. In conclusion, our findings clearly indicate that CAPS would be useful as a food supplement in assisting the treatment of Japanese cedar pollinosis. PMID:18071252

  19. Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study

    PubMed Central

    García-Gea, Consuelo; Ballester, Maria Rosa; Martínez, Juan; Antonijoan, Rosa Maria; Donado, Esther; Izquierdo, Iñaki; Barbanoj, Manuel-José

    2010-01-01

    AIM The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H1-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg. METHODS Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg. RESULTS Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated. CONCLUSION Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations. PMID:20565458

  20. A randomized, double-blind, placebo-controlled trial of selective digestive decontamination in a medical-surgical intensive care unit.

    PubMed

    Wiener, J; Itokazu, G; Nathan, C; Kabins, S A; Weinstein, R A

    1995-04-01

    A randomized, double-blind, placebo-controlled trial of selective decontamination of the oropharynx and gastrointestinal tract was conducted on 61 intubated patients in a medical-surgical intensive care unit (ICU) to determine the impact on nosocomial pneumonia, other infections, and emergence of colonization or infection with antibiotic-resistant bacteria. Over 8 months, 30 patients received an oral paste and solution containing polymyxin, gentamicin, and nystatin; 31 patients received a placebo paste and solution. At study entry, patients in both groups were seriously ill (mean acute physiologic score, 27.2), frequently had pulmonary infiltrates (73.8%), and were likely to be receiving systemic antibiotics (86.9%). There were no differences between study patients and control patients in these characteristics or in frequency of any nosocomial infection (50% vs. 55%), nosocomial pneumonia (27% vs. 26%), febrile days (2.3 vs. 2.0), duration of antibiotic therapy (14.0 vs. 13.4), or mortality rates (37% vs. 48%). There was no difference in infections caused by antibiotic-resistant gram-negative bacilli, although a trend towards more frequent infection with gentamicin-resistant enterococci was found for study patients. Selective decontamination did not appear to be effective in our very ill medical-surgical ICU patients, although the number of patients in our trial was sufficient to detect only a 50% or greater reduction in pneumonia rates.

  1. Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype.

    PubMed

    Miyaki, Koichi; Murata, Mitsuru; Kikuchi, Haruhito; Takei, Izumi; Nakayama, Takeo; Watanabe, Kiyoaki; Omae, Kazuyuki

    2005-01-01

    This study aimed at assessing the effect of folic acid supplementation quantitatively in each MTHFR C677T genotype and considered the efficiency of tailor-made prevention of atherosclerosis. Study design was genotype-stratified, randomized, double-blind, placebo-controlled trials. The setting was a Japanese company in the chemical industry. Subjects were 203 healthy men after exclusion of those who took folic acid or drugs known to effect folic acid metabolism. Intervention was folic acid 1 mg/day p.o. for 3 months. The primary endpoint was plasma total homocysteine level (tHcy). In all three genotypes, there were significant tHcy decreases. The greatest decrease was in the TT homozygote [6.61 (3.47-9.76) micromol/l] compared with other genotypes [CC: 2.59 (1.81-3.36), CT: 2.64 (2.16-3.13)], and there was a significant trend between the mutated allele number and the decrease. The tHcy were significantly lowered in all the genotypes, but the amount of the decrease differed significantly in each genotype, which was observed at both 1 and 3 months. Using these time-series data, the largest benefit obtained by the TT homozygote was appraised as 2.4 times compared with the CC homozygote. Taking into account the high allele frequency of this SNP, this quantitative assessment should be useful when considering tailor-made prevention of atherosclerosis with folic acid. PMID:15895286

  2. Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial.

    PubMed

    Oura, Hajimu; Iino, Masato; Nakazawa, Yosuke; Tajima, Masahiro; Ideta, Ritsuro; Nakaya, Yutaka; Arase, Seiji; Kishimoto, Jiro

    2008-12-01

    Adenosine upregulates the expression of vascular endothelial growth factor and fibroblast growth factor-7 in cultured dermal papilla cells. It has been shown that, in Japanese men, adenosine improves androgenetic alopecia due to the thickening of thin hair due to hair follicle miniaturization. To investigate the efficacy and safety of adenosine treatment to improve hair loss in women, 30 Japanese women with female pattern hair loss were recruited for this double-blind, randomized, placebo-controlled study. Volunteers used either 0.75% adenosine lotion or a placebo lotion topically twice daily for 12 months. Efficacy was evaluated by dermatologists and by investigators and in phototrichograms. As a result, adenosine was significantly superior to the placebo according to assessments by dermatologists and investigators and by self-assessments. Adenosine significantly increased the anagen hair growth rate and the thick hair rate. No side-effects were encountered during the trial. Adenosine improved hair loss in Japanese women by stimulating hair growth and by thickening hair shafts. Adenosine is useful for treating female pattern hair loss in women as well as androgenetic alopecia in men.

  3. Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Chinese subpopulation analysis of a double-blind, randomized, placebo-controlled study

    PubMed Central

    Wang, Gang; Cheng, Yan; Wang, Jia Ning; Wu, Sheng Hu; Xue, Hai Bo

    2016-01-01

    Background Depression in bipolar I disorder responds to the atypical antipsychotic olanzapine. This subpopulation analysis assessed whether olanzapine is superior to placebo specifically in the treatment of Chinese patients with bipolar I depression. Methods This was a subpopulation analysis of a 6-week, multicenter, double-blind, parallel, randomized, placebo-controlled trial among 12 Chinese study centers. Eligible inpatients and outpatients were randomized to olanzapine (5 to 20 mg/day) or placebo. Patients were primarily assessed by the Montgomery-Åsberg Depression Rating Scale total score. Secondary assessments used a range of other efficacy and safety measures. This subpopulation analysis was underpowered to show statistically significant differences between treatment groups. Results In total, 210 patients (mean age 32.9 years at baseline, 54.3% females) were random-ized. Similar proportions of patients treated with olanzapine (75.0%) and placebo (72.9%) completed the double-blind phase. Baseline-to-endpoint least-squares mean ± standard error decrease in the Montgomery-Åsberg Depression Rating Scale total score in the olanzapine group (−13.55±0.80) was similar to that noted in the parent trial (−13.82±0.65). However, the difference between olanzapine and placebo groups was not statistically significant (P=0.44); this finding was also true for the secondary efficacy measures. A post hoc analysis showed a greater emergence of mania in the placebo group, which likely reduced the treatment difference between olanzapine and placebo in the primary efficacy measure. Safety data were consistent with the known safety profile of olanzapine, including a higher incidence of weight gain (≥7%) in the olanzapine group (24.1% vs 1.4%, P<0.001). Conclusion Olanzapine provides similar improvement in depression among Chinese and non-Chinese bipolar I patients. The lack of a statistically significant difference between the olanzapine and placebo groups in this

  4. Efficacy and safety of olanzapine for treatment of patients with bipolar depression: Chinese subpopulation analysis of a double-blind, randomized, placebo-controlled study

    PubMed Central

    Wang, Gang; Cheng, Yan; Wang, Jia Ning; Wu, Sheng Hu; Xue, Hai Bo

    2016-01-01

    Background Depression in bipolar I disorder responds to the atypical antipsychotic olanzapine. This subpopulation analysis assessed whether olanzapine is superior to placebo specifically in the treatment of Chinese patients with bipolar I depression. Methods This was a subpopulation analysis of a 6-week, multicenter, double-blind, parallel, randomized, placebo-controlled trial among 12 Chinese study centers. Eligible inpatients and outpatients were randomized to olanzapine (5 to 20 mg/day) or placebo. Patients were primarily assessed by the Montgomery-Åsberg Depression Rating Scale total score. Secondary assessments used a range of other efficacy and safety measures. This subpopulation analysis was underpowered to show statistically significant differences between treatment groups. Results In total, 210 patients (mean age 32.9 years at baseline, 54.3% females) were random-ized. Similar proportions of patients treated with olanzapine (75.0%) and placebo (72.9%) completed the double-blind phase. Baseline-to-endpoint least-squares mean ± standard error decrease in the Montgomery-Åsberg Depression Rating Scale total score in the olanzapine group (−13.55±0.80) was similar to that noted in the parent trial (−13.82±0.65). However, the difference between olanzapine and placebo groups was not statistically significant (P=0.44); this finding was also true for the secondary efficacy measures. A post hoc analysis showed a greater emergence of mania in the placebo group, which likely reduced the treatment difference between olanzapine and placebo in the primary efficacy measure. Safety data were consistent with the known safety profile of olanzapine, including a higher incidence of weight gain (≥7%) in the olanzapine group (24.1% vs 1.4%, P<0.001). Conclusion Olanzapine provides similar improvement in depression among Chinese and non-Chinese bipolar I patients. The lack of a statistically significant difference between the olanzapine and placebo groups in this

  5. Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction

    PubMed Central

    2014-01-01

    Background Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. Methods and design This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3–6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. Discussion It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for

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

    PubMed Central

    Eskandarian, Tahereh; Eftekharian, Hamidreza; Soleymanzade, Rojin

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

    Abstract 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. PMID:27218868

  8. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial

    PubMed Central

    Tomusiak, Anna; Strus, Magdalena; Heczko, Piotr B; Adamski, Paweł; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena

    2015-01-01

    Objective The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score. Patients and methods The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4–6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag®, or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events. Results Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (P<0.05) and Nugent score (P<0.05), and a significant increase in the abundance of Lactobacillus between visit I and visits III and IV (P<0.05). Molecular typing revealed the presence of Lactobacillus strains originating from inVag in 82% of women taking the drug at visit III, and 47.5% at visit IV. There was no serious adverse event related to inVag administration during the study. Conclusion The probiotic inVag is safe for administration to sustainably restore the healthy vaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota. PMID:26451088

  9. Double blind randomized placebo controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis

    PubMed Central

    Dasarathy, Srinivasan; Dasarathy, Jaividhya; Khiyami, Amer; Yerian, Lisa; Hawkins, Carol; Sargent, Ruth; McCullough, Arthur Joseph

    2014-01-01

    Background Nonalcoholic steatohepatitis (NASH) is common and severe in patients with diabetes mellitus. Although, there are no effective treatments for NASH in diabetic patients, preliminary reports suggest that polyunsaturated fatty acids (PUFA) may be beneficial in these patients. Aim A prospective, randomized, double blind placebo controlled study (NCT 00323414) was performed in NASH patients with diabetes. Methods 37 patients (50.6±9.8y) with well controlled diabetes (HbA1C<8.5%) were randomized to receive either PUFA containing eicosapentaenoic acid 2160 mg and docosahexaenoic acid 1440 mg daily or an isocaloric, identical placebo containing corn oil for 48 weeks under CONSORT guidelines. Clinical, demographics, biochemical laboratory tests, body composition using DEXA® and liver biopsy were done at randomization and at the end of treatment. Liver biopsy was scored by the NASH CRN criteria. An intention to treat analysis was performed. Results At inclusion, gender, age, body weight, biochemical tests, glucose control and liver histology were similar in the 2 treatment groups. There was no change in liver enzymes, body weight or body composition during the study in either group. At the end of treatment, hepatic steatosis and the activity score improved (p<0.05) and lobular inflammation worsened (p<0.001) with placebo but was unchanged with PUFA. At the end of treatment, insulin resistance (serum glucose and HOMA) worsened with PUFA but not placebo. Conclusions PUFA provided no benefit over placebo in NASH patients with diabetes. The effects of PUFA on histology and insulin resistance were inferior to placebo. These data provide no support for PUFA supplements in NASH. PMID:24583757

  10. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim

    2016-01-01

    Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485

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

    PubMed

    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.

  12. Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Hansen, Melissa Voigt; Madsen, Michael Tvilling; Andersen, Lærke Toftegård; Hageman, Ida; Rasmussen, Lars Simon; Bokmand, Susanne; Rosenberg, Jacob; Gögenur, Ismail

    2014-01-01

    Background. Sleep disturbances and cognitive dysfunction are common in patients with breast cancer. Disturbed sleep leads to poor cognitive performance and exogenous melatonin may improve sleep and attenuate cognitive dysfunction. We hypothesized that melatonin would improve sleep and cognitive function after surgery. Methods. This study reports secondary endpoints from a randomized, double-blind, placebo-controlled trial. Women, 30-75 years, were randomized to 6mg oral melatonin/placebo for 3 months. We assessed postoperative cognitive dysfunction (POCD) with a neuropsychological test battery, sleep with a diary, and sleep quality with VAS. Results. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26); 11 withdrew (10 placebo, 1 melatonin, P = 0.002). The incidence of POCD was 0% (0/20) [95% CI 0.0%; 16.8%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 2 weeks postoperatively (P = 1.00) and 6.3% (1/16) [95% CI 0.0%; 30.2%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 12 weeks postoperatively (P = 0.38). Sleep efficiency was significantly greater in the melatonin group; mean difference was 4.28% [95% CI 0.57; 7.82] (P = 0.02). The total sleep period was significantly longer in the melatonin group; mean difference was 37.0 min [95% CI 3.6; 69.7] (P = 0.03). Conclusion. Melatonin increased sleep efficiency and total sleep time but did not affect cognitive function. The dropout rate was significantly lower in the melatonin group. This trial is registered with Clinicaltrials.gov NCT01355523. PMID:25328711

  13. Recombinant Human Growth Hormone and Rosiglitazone for Abdominal Fat Accumulation in HIV-Infected Patients with Insulin Resistance: A Randomized, Double-Blind, Placebo-Controlled, Factorial Trial

    PubMed Central

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

    2013-01-01

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

  14. A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40–120 mg/day) in patients with major depressive disorder

    PubMed Central

    Gommoll, Carl P.; Greenberg, William M.; Chen, Changzheng

    2014-01-01

    Objective Levomilnacipran ER is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). Efficacy and safety have been evaluated in five Phase II/III studies, four of which met the pre-specified primary efficacy outcome. Results of the negative trial (ClinicalTrials.gov NCT00969150) are reported here. Methods A Phase III randomized, double-blind, placebo-controlled trial comparing flexible-dose levomilnacipran ER 40–120 mg/day with placebo was conducted in outpatients with MDD. Patients met the DSM-IV-TR criteria for MDD, had a current episode of depression of at least 4 weeks’ duration, and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥30. The study comprised a 1-week, single-blind, placebo lead-in, 8-week double-blind treatment, and a 2-week down-taper. The primary and secondary efficacy measures were change from baseline to Week 8 in MADRS and Sheehan Disability Scale (SDS) total scores, respectively, analyzed using a mixed-effects model for repeated measures approach. Safety outcomes included adverse events (AEs), laboratory and vital sign measures, the Columbia-Suicide Severity Rating Scale, and the Arizona Sexual Experiences Scale (ASEX). Results Three hundred and fifty-five patients received the study drug and had ≥1 post-baseline MADRS total score assessment (ITT Population); 81.9% of placebo and 77.1% of levomilnacipran ER patients completed the study. For levomilnacipran ER vs placebo, MADRS (−15.7 vs −14.2) and SDS (−8.8 vs −8.2) total score improvements, and rates of MADRS response (38.5% vs 34.8%) and remission (25.3% vs 23.8%) were numerically greater but differences were not statistically significant. Levomilnacipran ER was generally well tolerated. More levomilnacipran ER patients vs placebo reported AEs; the most common AEs for levomilnacipran ER were nausea (17%) and headache (16%). Mean changes in most safety measures were

  15. Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study

    PubMed Central

    Bakish, David; Bose, Anjana; Gommoll, Carl; Chen, Changzheng; Nunez, Rene; Greenberg, William M.; Liebowitz, Michael; Khan, Arif

    2014-01-01

    Background Major depressive disorder (MDD) is a global health concern. This study examined the efficacy, safety and tolerability of an extended-release (ER) formulation of levomilnacipran, an antidepressant approved for the treatment of MDD in adults. Methods This 10-week (1-week placebo run-in period, 8-week double-blind treatment, 1-week down-taper), multicentre, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted between June 2011 and March 2012. Adult outpatients (age 18–75 yr) with MDD were randomly assigned (1:1:1) to placebo or to levomilnacipran ER 40 mg/day or 80 mg/day. For primary efficacy, we analyzed the Montgomery–Åsberg Depression Rating Scale (MADRS) change from baseline to week 8 using a mixed-effects model for repeated-measures approach on the intent-to-treat (ITT) population. For secondary efficacy, we used the Sheehan Disability Scale (SDS), and for safety, we examined adverse events and laboratory, vital sign/physical and electrocardiography findings. Results The ITT population consisted of 185 patients in the placebo group, 185 in the levomilnacipran ER 40 mg/day group and 187 in the levomilnacipran ER 80 mg/day group. Study completion rates were similar among the groups (76%–83%). On MADRS change from baseline the least squares mean difference (LSMD) and 95% confidence interval (CI) versus placebo was significant for levomilnacipran ER 40 mg/day (–3.3 [−5.5 to −1.1], p = 0.003) and 80 mg/day (−3.1, [−5.3 to −1.0], p = 0.004). On SDS change from baseline the LSMD (and 95% CI) versus placebo was also significant for levomilnacipran ER 40 mg/day (−1.8, 95% [−3.6 to 0], p = 0.046) and 80 mg/day (−2.7 [−4.5 to −0.9], p = 0.003). More patients in the levomilnacipran ER than the placebo group prematurely exited the study owing to adverse events; common adverse events (≥ 5% and ≥ double the rate of placebo) were nausea, dry mouth, increased heart rate, constipation, dizziness

  16. Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial

    PubMed Central

    Gerami, Hooshang; Nemati, Shadman; Kazemnejad, Ehsan; Aghajanpour, Mohammad

    2012-01-01

    Background It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus. Methods In a randomized double–blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day), oxcarbazepine (450-900 mg/day) and placebo for 12 weeks. Visual analogue scale (VAS) and tinnitus severity index (TSI) were measured in all subjects in the beginning and at the end of the 8th and 12th weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test. Results Among 51 participants who completed the trial course (28 men, 23 women), carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28). Conclusion Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity. PMID:24250874

  17. Ultrasonographic evaluation of plantar fasciitis after low-level laser therapy: results of a double-blind, randomized, placebo-controlled trial.

    PubMed

    Kiritsi, Olga; Tsitas, Konstantinos; Malliaropoulos, Nikolaos; Mikroulis, Grogorios

    2010-03-01

    The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on plantar fasciitis documented by the ultrasonographic appearance of the aponeurosis and by patients' pain scores. Thirty individuals with diagnosis of unilateral plantar fasciitis were enrolled in a randomized, double-blind, placebo-controlled trial, but 25 participants completed the therapeutic protocol. The contralateral asymptomatic fascia was used as control. After enrolment, symptomatic individuals were randomly assigned to receive LLLT, or identical placebo, for 6 weeks. Ultrasonography was performed at baseline and after completion of therapy. The subjective subcalcaneal pain was recorded at baseline and after treatment on a visual analogue scale (VAS). After LLLT, plantar fascia thickness in both groups showed significant change over the experimental period and there was a difference (before treatment and after treatment) in plantar fascia thickness between the two groups. However, plantar fascia thickness was insignificant (mean 3.627 +/- 0.977 mm) when compared with that in the placebo group (mean 4.380 +/- 1.0042 mm). Pain estimation on the visual analogue scale had improved significantly in all test situations (after night rest, daily activities) after LLLT when compared with that of the placebo group. (P=0.006 and P=0.01, respectively). Additionally, when the difference in pain scores was compared between the two groups, the change was statistically significant (after night rest P=0.000; daily activities P=0.001). In summary, while ultrasound imaging is able to depict the morphologic changes related to plantar fasciitis, 904 nm gallium-arsenide (GaAs) infrared laser may contribute to healing and pain reduction in plantar fasciitis.

  18. The effect of herbal extract (EstroG-100) on pre-, peri- and post-menopausal women: a randomized double-blind, placebo-controlled study.

    PubMed

    Chang, Albert; Kwak, Bo-Yeon; Yi, Kwontaek; Kim, Jae Soo

    2012-04-01

    This clinical research study was designed to evaluate the efficacy of a new herbal product, EstroG-100, containing a mixture of standardized extracts of Cynanchum wilfordii, Phlomis umbrosa and Angelica gigas, on menopausal symptoms. This randomized double-blind, placebo-controlled trial was performed for 12 weeks with 64 pre-, peri- and postmenopausal White Hispanic, White non-Hispanic and African American women who were randomly allocated to either the EstroG-100 group (n = 31) or the placebo group (n =  33). Primary end-points were the mean change in scores of the Kupperman menopause index (KMI) that evaluates 11 symptoms, and the mean change in scores of vaginal dryness. The mean KMI score was significantly reduced in the EstroG-100 group from 29.5 ± 7.4 at baseline to 11.3 ± 5.8 (p < 0.01) compared with change of the placebo group (29.2 ± 6.6 at baseline vs 23.7 ± 7.7 at week 12). The constituting symptoms of vasomotor, paresthesia, insomnia, nervousness, melancholia, vertigo, fatigue and rheumatic pain were significantly improved in the EstroG-100 group in comparison with the placebo group (p < 0.05). Statistically significant improvement in vaginal dryness in the EstroG-100 group was also observed compared with that of the placebo group (p < 0.05). In conclusion, EstroG-100 significantly improved the menopausal symptoms of pre-, peri- and post-menopausal women without weight gain or any serious side effects.

  19. Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model: a randomized, double-blind, placebo-controlled, three-arm crossover study.

    PubMed

    Andersen, Lars P H; Gögenur, Ismail; Fenger, Andreas Q; Petersen, Marian C; Rosenberg, Jacob; Werner, Mads U

    2015-11-01

    Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models. The aim of this study was to investigate the analgesic, antihyperalgesic, and anti-inflammatory properties of melatonin using a validated burn injury (BI) model in healthy male volunteers. The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in 3 identical study sessions with intravenous administration of placebo, melatonin 10 mg, or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined as primary outcomes. Twenty-nine volunteers were randomized and completed the study. While the BI induced large secondary hyperalgesia areas and significantly increased the markers of inflammation, no significant effects of melatonin were observed with respect to primary or secondary outcomes, compared with placebo. The administration of melatonin was not associated with any adverse effects. Melatonin did not demonstrate any analgesic, antihyperalgesic, or anti-inflammatory properties in the BI model. PMID:26164585

  20. Randomized, placebo-controlled, double-blind clinical trial evaluating the treatment of plantar fasciitis with an extracoporeal shockwave therapy (ESWT) device: a North American confirmatory study.

    PubMed

    Kudo, Patricia; Dainty, Katie; Clarfield, Michael; Coughlin, Larry; Lavoie, Pauline; Lebrun, Constance

    2006-02-01

    Despite numerous publications and clinical trials, the results of treatment of recalcitrant chronic plantar fasciitis with extracorporeal shockwave therapy (ESWT) still remain equivocal as to whether or not this treatment provides relief from the pain associated with this condition. The objective of this study was to determine whether extracorporeal shock wave therapy can safely and effectively relieve the pain associated with chronic plantar fasciitis compared to placebo treatment, as demonstrated by pain with walking in the morning. This was set in a multicenter, randomized, placebo-controlled, double-blind, confirmatory clinical study undertaken in four outpatient orthopedic clinics. The patients, 114 adult subjects with chronic plantar fasciitis, recalcitrant to conservative therapies for at least 6 months, were randomized to two groups. Treatment consisted of approximately 3,800 total shock waves (+/-10) reaching an approximated total energy delivery of 1,300 mJ/mm(2) (ED+) in a single session versus placebo treatment. This study demonstrated a statistically significant difference between treatment groups in the change from baseline to 3 months in the primary efficacy outcome of pain during the first few minutes of walking measured by a visual analog scale. There was also a statistically significant difference between treatments in the number of participants whose changes in Visual Analog Scale scores met the study definition of success at both 6 weeks and 3 months posttreatment; and between treatment groups in the change from baseline to 3 months posttreatment in the Roles and Maudsley Score. The results of this study confirm that ESWT administered with the Dornier Epos Ultra is a safe and effective treatment for recalcitrant plantar fasciitis.

  1. Effects of Probiotics on Biomarkers of Oxidative Stress and Inflammatory Factors in Petrochemical Workers: A Randomized, Double-blind, Placebo-controlled Trial

    PubMed Central

    Mohammadi, Ali Akbar; Jazayeri, Shima; Khosravi-Darani, Kianoush; Solati, Zahra; Mohammadpour, Nakisa; Asemi, Zatollah; Adab, Zohre; Djalali, Mahmoud; Tehrani-Doost, Mehdi; Hosseini, Mostafa; Eghtesadi, Shahryar

    2015-01-01

    Background: The aim of the current study was to determine effects of probiotic yoghurt and multispecies probiotic capsule supplementation on biomarkers of oxidative stress and inflammatory factors in petrochemical workers. Methods: This randomized, double-blind, placebo-controlled trial was done among petrochemical workers. Subjects were randomly divided into three groups to receive 100 g/day probiotic yogurt (n = 12) or one probiotic capsule daily (n = 13) or 100 g/day conventional yogurt (n = 10) for 6 weeks. The probiotic yoghurt was containing two strains of Lactobacillus acidophilus and Bifidobacterium lactis with a total of min 1 × 107 CFU. Multispecies probiotic capsule contains seven probiotic bacteria spices Actobacillus casei 3 × 103, L. acidophilus 3 × 107, Lactobacillus rhamnosus 7 × 109, Lactobacillus bulgaricus 5 × 108, Bifidobacterium breve 2 × 1010, Bifidobacterium longum 1 × 109 and Streptococcus thermophilus 3 × 108 CFU/g. Fasting blood samples were obtained at the beginning and end of the trial to quantify biomarkers of oxidative stress and inflammatory factors. Results: Although a significant within-group decrease in plasma protein carbonyl levels was seen in the probiotic capsule group (326.0 ± 308.9 vs. 251.0 ± 176.3 ng/mL, P = 0.02), the changes were similar among the three groups. In addition, significant within-group decreases in plasma iso prostaglandin were observed in the probiotic supplements group (111.9 ± 85.4 vs. 88.0 ± 71.0 pg/mL, P = 0.003) and in the probiotic yogurt group (116.3 ± 93.0 vs. 92.0 ± 66.0 pg/mL, P = 0.02), nevertheless there were no significant change among the three groups. Conclusions: Taken together, consumption of probiotic yogurt or multispecies probiotic capsule had beneficial effects on biomarkers of oxidative stress in petrochemical workers. PMID:26445629

  2. Efficacy and tolerability of a novel herbal formulation for weight management in obese subjects: a randomized double blind placebo controlled clinical study

    PubMed Central

    2012-01-01

    Background The effect of an herbal formulation LI85008F on weight loss in obese human subjects was evaluated in an 8-weeks randomized, double-blind, placebo-controlled study (Clinical Trial Registration no. ISRCTN37381706). Fifty obese subjects (Body mass index 30 to 40 kg/m², 29.3% male; 70.7% female; ages 27–50 years) were randomized into two groups; placebo (n = 25) and LI85008F formulation (n = 25). The participants received either 900 mg/day of LI85008F formulation in three divided doses or three identical placebo capsules and all of them remained on a calorie-controlled diet (2000 cal/day) and 30 min walking for 5 days a week during the entire duration of the study. Results and discussion At the end of the trial period, LI85008F supplemented group showed significant net reductions in body weight and Body Mass Index (BMI). The participants who received the herbal formulation, showed reduced fasting blood glucose, LDL, LDL/HDL ratio, and triglycerides. At the end of the study, LI85008F supplementation also provided 21.26% (p = 0.012) increase in serum adiponectin level, compared with the placebo group. No major adverse events were reported by the participants in the study duration. In addition, Adipokine profiling study in 3T3-L1 adipocytes demonstrates that LI85008F modulates key regulatory factors of adipogenic differentiation and insulin sensitivity, such as Adiponectin, Pref-1, and resistin. Conclusion The herbal formulation LI85008F (Adipromin) is prepared from commonly used medicinal plants extracts, which provides useful and safe application for weight loss in obese humans. It also demonstrates potential promise in controlling healthy blood glucose level in obesity linked type 2 diabetes. PMID:22995673

  3. Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

    PubMed

    Pandaran Sudheeran, Subash; Jacob, Della; Natinga Mulakal, Johannah; Gopinathan Nair, Gopakumar; Maliakel, Abhilash; Maliakel, Balu; Kuttan, Ramadasan; Im, Krishnakumar

    2016-06-01

    Drug delivery systems capable of delivering free (unconjugated) curcuminoids is of great therapeutic significance, since the absorption of bioactive and permeable form plays a key factor in mediating the efficacy of a substance which undergoes rapid biotransformation. Considering the recent understanding on the relatively high bioactivities and blood-brain-barrier permeability of free curcuminoids over their conjugated metabolites, the present human study investigated the safety, antioxidant efficacy, and bioavailability of CurQfen (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin with fenugreek dietary fiber that has shown to possess improved blood-brain-barrier permeability and tissue distribution in rats. In this randomized double-blinded and placebo-controlled trial, 60 subjects experiencing occupational stress-related anxiety and fatigue were randomized to receive CGM, standard curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated the safety, tolerance, and enhanced efficacy of CGM in comparison with unformulated standard curcumin. A significant improvement in the quality of life (P < 0.05) with considerable reduction in stress (P < 0.001), anxiety (P < 0.001), and fatigue (P < 0.001) was observed among CGM-treated subjects as compared with the standard curcumin group, when monitored by SF-36, Perceived Stress Scale with 14 items, and Beck Anxiety Inventory scores. Improvement in the quality of life was further correlated with the significant enhancement in endogenous antioxidant markers (P < 0.01) and reduction in lipid peroxidation (P < 0.001). Further comparison of the free curcuminoids bioavailability after a single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30 days) oral administration revealed enhanced absorption and improved pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1-fold) administrations. PMID:27043120

  4. XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind, placebo-controlled, dose-escalating study

    PubMed Central

    Deloche, Catherine; Lopez-Lazaro, Luis; Mouz, Sébastien; Perino, Julien; Abadie, Claire; Combette, Jean-Marc

    2014-01-01

    The aim of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of the JNK inhibitor XG-102 in a randomized, double blind, placebo controlled, sequential ascending dose parallel group Phase 1 Study. Three groups of male subjects received as randomly assigned ascending single XG-102 doses (10, 40, and 80 μg/kg; 6 subjects per dose) or placebo (2 subjects per dose) as an intravenous (IV) infusion over 60 min. Safety and tolerability were assessed by physical examination, vital signs, electrocardiography, eye examination, clinical laboratory tests and adverse events (AEs). PK was analyzed using noncompartmental methods. All reported AEs were mild to moderate and neither their number nor their distribution by System Organ Class suggest a dose relationship. Only headache and fatigue were considered probably or possibly study drug related. Headache frequency was similar for active and placebo, consequently this was not considered to be drug related but probably to study conditions. The other examinations did not show clinically relevant deviations or trends suggesting a XG-102 relationship. Geometric mean half-life was similar among doses, ranging from 0.36 to 0.65 h. Geometric mean XG-102 AUC0–last increased more than linearly with dose, 90% confidence intervals (CIs) did not overlap for the two highest doses. Geometric mean dose normalized Cmax values suggest a more than linear increase with dose but 90% CIs overlap. It may be concluded that XG-102 single IV doses of 10–80 μg/kg administered over 1 h to healthy male subjects were safe and well tolerated. PMID:25505576

  5. Randomized Double-blind Placebo-controlled Trial of Celecoxib for Oral Mucositis in Patients Receiving Radiation Therapy for Head and Neck Cancer

    PubMed Central

    Lalla, Rajesh V.; Choquette, Linda E.; Curley, Kathleen F.; Dowsett, Robert J.; Feinn, Richard S.; Hegde, Upendra P.; Pilbeam, Carol C.; Salner, Andrew L.; Sonis, Stephen T.; Peterson, Douglas E.

    2016-01-01

    Objectives Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer (H&NC). OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to treatment interruptions. Based on the role of inflammatory pathways in OM pathogenesis, we investigated effect of cyclooxygenase-2 (COX-2) inhibition on severity and morbidity of OM. Methods In this double-blind placebo-controlled trial, 40 H&NC patients were randomized to daily use of 200 mg celecoxib or placebo, for the duration of RT. Clinical OM, normalcy of diet, pain scores, and analgesic use were assessed 2–3 times/week by blinded investigators during the 6–7 week RT period, using validated scales. Results Twenty subjects were randomized to each arm, which were similar with respect to tumor location, radiation dose, and concomitant chemotherapy. In both arms, mucositis and pain scores increased over course of RT. Intention-to-treat analyses demonstrated no significant difference in mean Oral Mucositis Assessment Scale (OMAS) scores at 5000 cGy (primary endpoint). There was also no difference between the two arms in mean OMAS scores over the period of RT, mean worst pain scores, mean normalcy of diet scores, or mean daily opioid medication use in IV morphine equivalents. There were no adverse events attributed to celecoxib use. Conclusions Daily use of a selective COX-2 inhibitor, during period of RT for H&NC, did not reduce the severity of clinical OM, pain, dietary compromise or use of opioid analgesics. These findings also have implications for celecoxib use in H&NC treatment regimens (NCT00698204). PMID:25151488

  6. Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model: a randomized, double-blind, placebo-controlled, three-arm crossover study.

    PubMed

    Andersen, Lars P H; Gögenur, Ismail; Fenger, Andreas Q; Petersen, Marian C; Rosenberg, Jacob; Werner, Mads U

    2015-11-01

    Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models. The aim of this study was to investigate the analgesic, antihyperalgesic, and anti-inflammatory properties of melatonin using a validated burn injury (BI) model in healthy male volunteers. The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in 3 identical study sessions with intravenous administration of placebo, melatonin 10 mg, or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined as primary outcomes. Twenty-nine volunteers were randomized and completed the study. While the BI induced large secondary hyperalgesia areas and significantly increased the markers of inflammation, no significant effects of melatonin were observed with respect to primary or secondary outcomes, compared with placebo. The administration of melatonin was not associated with any adverse effects. Melatonin did not demonstrate any analgesic, antihyperalgesic, or anti-inflammatory properties in the BI model.

  7. Bupropion for the Treatment of Methamphetamine Dependence in Non-Daily Users: a Randomized, Double-Blind, Placebo-Controlled Trial*

    PubMed Central

    Anderson, Ann L.; Li, Shou-Hua; Markova, Denka; Holmes, Tyson H.; Chiang, Nora; Kahn, Roberta; Campbell, Jan; Dickerson, Daniel L.; Galloway, Gantt P.; Stock, Christopher; Elkashef, Ahmed M.

    2015-01-01

    Aims Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users. Methods A randomized, double-blind, placebo-controlled trial, with 12-week treatment and 4-week follow-up, was conducted with 204 treatment-seeking participants having MA dependence per DSM-IV, who used MA on a less-than-daily basis. 104 were randomized to matched placebo and 100 to bupropion, sustained-release 150mg, twice daily. Participants were seen three times weekly to obtain urine for MA and bupropion assays, study assessments, and thrice weekly, 90-minute, group psychotherapy. There was no biomarker for placebo adherence. The primary outcome was achievement of abstinence throughout the last two weeks of treatment; ‘success’ requiring at least two urine samples during each of Weeks 11 and 12, and all samples MA-negative (<300ng/mL). Results Bupropion and placebo groups did not differ significantly in the percentage achieving abstinence for the last 2 weeks of treatment (chi-square, p=0.32). Subgroup analysis of participants with lower baseline MA use (≤18 of last 30 days before consent) also revealed no difference in success between groups (p=0.73). Medication adherence per protocol (detectable bupropion, >5ng/mL, in ≥50% of urine samples from Study Weeks 1–10 and ≥66% of urine samples from Weeks 11–12) was achieved by 47% of participants taking bupropion. Conclusions These data indicate that bupropion did not increase abstinence in dependent participants who were using MA less-than-daily. Medication non-adherence was a limitation in this trial. Psychosocial therapy remains the mainstay of treatment for MA dependence. Further research on subgroups who may respond to bupropion may be warranted. Trial Registration www.ClinicalTrials.gov : NCT00687713. PMID:25818061

  8. Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial1

    PubMed Central

    Owens, Stephen; Gulati, Ruchi; Fulford, Anthony J; Sosseh, Fatou; Denison, Fiona C; Brabin, Bernard J; Prentice, Andrew M

    2015-01-01

    Background: Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction. Objective: We tested the hypothesis that periconceptional multiple-micronutrient supplementation (MMS) affects placental function. Design: We conducted a double-blind, randomized, placebo-controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo. Eligible subjects were pre–randomly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation (UNIMMAP) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive. Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ratio of plasminogen-activator inhibitor (PAI) 1 to PAI-2 and mean uterine-artery resistance index (UtARI)] and placental active transport capacity at delivery [fetal to maternal measles antibody (MMA) ratio]. Results: We recruited 1156 women who yielded 415 pregnancies, of which 376 met all of the inclusion criteria. With adjustment for gestational age at sampling, there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms, but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation (95% CI: −0.03, −0.00; P = 0.040) in women taking UNIMMAP. Conclusions: Placental vascular function was modifiable by periconceptional micronutrient supplementation. However, the effect was small and supplementation did not further affect other variables of placental function. This trial was registered at www.controlled-trials.com as ISRCTN 13687662. PMID:26561613

  9. Effects of Platelet Rich Plasma on Healing Rate of Long Bone Non-union Fractures: A Randomized Double-Blind Placebo Controlled Clinical Trial

    PubMed Central

    Ghaffarpasand, Fariborz; Shahrezaei, Mostafa; Dehghankhalili, Maryam

    2016-01-01

    Objective: To determine the effects of platelet rich plasma PRP on healing rates of long bone non-union fracture. Method: This was a randomized double-blind placebo controlled clinical trial being performed in a 12-month period. We included 75 adult (>18 years) patients suffering from long bone (Femur, Tibia, Humerus and Ulna) non-union fracture who were randomly assigned to receive 5mL PRP (n=37) or 5mL normal saline as placebo (n=38) in the site of fracture after intramedullary nailing or open reduction and internal fixation (ORIF) along with autologous bone graft. Patients were followed each 45 days till 9 months and were evaluated both clinically and radiologically in each visit. The healing rate, failure rate, incidence of infection, mal-union and limb shortening were recorded and compared between groups after 9 months of follow-up. Results: The healing rate was significantly higher in PRP group compared to placebo (81.1% vs. 55.3%; p=0.025). The limb shortening was significantly higher in those who received placebo (2.61±1.5 vs. 1.88±1.2mm; p=0.030). Injection of PRP was also associated with lower pain scores ( p=0.003) and shorter healing duration ( p=0.046). The surgical site infection ( p=0.262) and mal-union rate ( p=0.736) were comparable between groups. Conclusion: Application of PRP along with autologous bone graft in the site of non-union of long bone after intramedullary nailing or ORIF results in higher cure rate, shorter healing duration, lower limb shortening and less postoperative pain. Higher infection rate might be a complication of PRP application. Clinical Trial Registry: This trial is registered with the Iranian Clinical Trials Registry (IRCT201208262445N1; www.irct.ir). PMID:27540547

  10. Preemptive Analgesic Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Postoperative Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Eidy, Mohammad; Fazel, Mohammad Reza; Janzamini, Monir; Haji Rezaei, Mostafa; Moravveji, Ali Reza

    2016-01-01

    Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological analgesic method used to control different types of pain. Objectives The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. Patients and Methods This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. Results The mean estimated postoperative pain intensity was 6.21 ± 1.63 in the intervention group and 5.45 ± 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 ± 1.48 and 5.12 ± 1.41 (P < 0.001), respectively. In the control group these values were 4.0±1.5 and 4.76 ± 1.39 (P = 0.04), respectively. No significant differences were observed in mean pain intensities at 6 and 12 hours. Conclusions TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery. PMID:27275401

  11. Daily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    Nagatomo, Akifumi; Nishida, Norihisa; Fukuhara, Ikuo; Noro, Akira; Kozai, Yoshimichi; Sato, Hisao; Matsuura, Yoichi

    2015-01-01

    Background Obesity has become a great problem all over the world. We repeatedly screened to find an effective food to treat obesity and discovered that rosehip extract shows potent anti-obesity effects. Investigations in mice have demonstrated that rosehip extract inhibits body weight gain and decreases visceral fat. Thus, the present study examined the effect of rosehip extract on human body fat in preobese subjects. Methods We conducted a 12-week, single-center, double-blind, randomized, placebo-controlled study of 32 subjects who had a body mass index of ≥25 but <30. The subjects were assigned to two random groups, and they received one tablet of placebo or rosehip that contained 100 mg of rosehip extract once each day for 12 weeks with no dietary intervention. Abdominal fat area and body fat percent were measured as primary outcomes. The other outcomes were body weight and body mass index. Results Abdominal total fat area, abdominal visceral fat area, body weight, and body mass index decreased significantly in the rosehip group at week 12 compared with their baseline levels (P<0.01) after receiving the rosehip tablet intake, and the decreases in these parameters were significantly higher when compared with those in the placebo group. Additionally, body fat percent tended to decrease compared with the placebo group and their baseline level. Moreover, the abdominal subcutaneous fat area was significantly lower in the rosehip group than in the placebo group at week 12 after the initiation of intake (P<0.05). In addition, there were no abnormalities, subjective symptoms, and findings that may indicate clinical problems during the study period. Conclusion These results suggest that rosehip extract may be a good candidate food material for preventing obesity. PMID:25834460

  12. Improvement of skin condition by oral supplementation with sphingomyelin-containing milk phospholipids in a double-blind, placebo-controlled, randomized trial.

    PubMed

    Higurashi, S; Haruta-Ono, Y; Urazono, H; Kobayashi, T; Kadooka, Y

    2015-10-01

    Sphingomyelin (SM), an essential phospholipid for the skin, is contained largely in the milk fat globule membrane surrounding milk fat, concentrated fractions of which are also generated concurrently during the manufacture of dairy products. Such an SM-containing milk phospholipid concentrate (SM-MPC) is useful for investigating the benefits of dietary SM. Here, we examined the effect of consuming SM-MPC on the condition of skin in a double-blind, placebo-controlled, randomized trial. Ninety-six healthy subjects aged 20 to 39 yr with low skin hydration were randomly assigned to 3 groups: a high-SM group supplemented with SM-MPC at a dose equivalent to 10 mg/d of SM, a low-SM group supplemented with SM-MPC equivalent to 5 mg/d of SM, and a placebo group fed a vehicle composed of olive oil and beeswax. During daily supplementation for 12 wk, parameters related to the condition of skin were evaluated at baseline and every 3 wk. Skin hydration at the heel was significantly increased at wk 9 and 12 in the low-SM group compared with the placebo group. Skin elasticity in the region below the eye was significantly increased at wk 9 in the high-SM group versus placebo. Questionnaire-based subjective perceptions of skin conditions were significantly improved for facial skin moisture at wk 3 and 12, and in the wrinkle around the eyes at wk 9 and 12 in the high-SM group versus placebo. Our results indicate that constant and long-term supplementation with SM-MPC is capable of improving the general condition of skin.

  13. Effects of Cactus Fiber on the Excretion of Dietary Fat in Healthy Subjects: A Double Blind, Randomized, Placebo-Controlled, Crossover Clinical Investigation

    PubMed Central

    Uebelhack, Ralf; Busch, Regina; Alt, Felix; Beah, Zhi-Ming; Chong, Pee-Win

    2014-01-01

    Background Cactus (Opuntia ficus-indica) fiber was shown to promote weight loss in a 3-month clinical investigation. As demonstrated by in vitro studies, cactus fiber binds to dietary fat and its use results in reduced absorption, which in turn leads to reduced energy absorption and ultimately the reduction of body weight. Objective The objective of our study was to elucidate the dietary fat binding capacity of cactus fiber through determination of fecal fat excretion in healthy volunteers. Subjects and Methods This clinical investigation was performed as a double-blind, randomized, placebo-controlled, crossover study in healthy subjects for a period of approximately 45 days. Twenty healthy volunteer subjects were randomized to receive cactus fiber or placebo, 2 tablets thrice daily with main meals. All subjects were provided with meals during the study period (except washout) according to a standardized meal plan, with 35% of daily energy need coming from fat. Two 24-hour feces samples were collected during both the baseline and treatment periods for analysis of the fat content. Results Cactus fiber showed an increased fecal fat excretion compared with placebo (mean [SD] = 15.79% [5.79%] vs 4.56% [3.09%]; P < 0.001). No adverse events were reported throughout the study period. Conclusions Cactus fiber has been shown to significantly promote fecal fat excretion in healthy adults. The results of our study support the hypothesis that cactus fiber helps in reducing body weight by binding to dietary fat and increasing its excretion, thus reducing dietary fat available for absorption. ClinicalTrials.gov identifier: NCT01590667. PMID:25067985

  14. Homeopathic medicine for acute cough in upper respiratory tract infections and acute bronchitis: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Zanasi, Alessandro; Mazzolini, Massimiliano; Tursi, Francesco; Morselli-Labate, Antonio Maria; Paccapelo, Alexandro; Lecchi, Marzia

    2014-02-01

    Cough is a frequent symptom associated to upper respiratory tract infections (URTIs) and, although being self-limiting, it might deeply affect the quality of life. Homeopathic products are often employed by patients to treat cough, but the evidence on their efficacy is scarce. Thus, we tested the efficacy of a homeopathic syrup in treating cough arising from URTIs with a randomized, double blind, placebo controlled clinical trial. Patients were treated with either the homeopathic syrup or a placebo for a week, and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks. Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment; patients were also asked to provide a subjective evaluation of viscosity. Eighty patients were randomized to receive placebo (n = 40) or the homeopathic syrup (n = 40). All patients completed the study. In each group cough scores decreased over time, however, after 4 and 7 days of treatment, cough severity was significantly lower in the homeopathic group than in the placebo one (p < 0.001 and p = 0.023, respectively). Sputum was collected from 53 patients: in both groups its viscosity significantly decreased after 4 days of treatment (p < 0.001); however, viscosity was significantly lower in the homeopathic group (p = 0.018). Instead, the subjective evaluation did not significantly differ between the two groups (p = 0.059). No adverse events related to any treatment were reported. We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity, thereby representing a valid remedy for the management of acute cough induced by URTIs. PMID:23714686

  15. Prophylactic tamsulosin (Flomax) in patients undergoing prostate {sup 125}I brachytherapy for prostate carcinoma: Final report of a double-blind placebo-controlled randomized study

    SciTech Connect

    Elshaikh, Mohamed A.; Ulchaker, James C.; Reddy, Chandana A.; Angermeier, Kenneth W.; Klein, Eric A.; Chehade, Nabil; Altman, Andrew; Ciezki, Jay P. . E-mail: ciezkj@ccf.org

    2005-05-01

    Purpose: To evaluate the effectiveness of prophylactic tamsulosin (Flomax) in reducing the urinary symptoms in patients undergoing {sup 125}I prostate implantation (PI) for prostate adenocarcinoma. Methods and materials: This is a single-institution, double-blind, placebo-controlled, randomized trial for patients undergoing PI for prostate adenocarcinoma comparing prophylactic tamsulosin versus placebo. Eligibility criteria included patients not taking tamsulosin or other {alpha}-blockers treated with PI. The patients were randomly assigned to either tamsulosin (0.8 mg, orally once a day) or matched placebo. All patients started the medication 4 days before PI and continued for 60 days. The American Urologic Association (AUA) symptom index questionnaire was used to assess urinary symptoms. The AUA questionnaire was administered before PI for a baseline score and weekly for 8 weeks after PI. Patients were taken off the study if they developed urinary retention, had intolerable urinary symptoms, or wished to discontinue with the trial. Results: One hundred twenty-six patients were enrolled in this study from November 2001 to January 2003 (118 were evaluable: 58 in the tamsulosin arm and 60 in the placebo group). Pretreatment and treatment characteristics were comparably matched between the two groups. The urinary retention rate was 17% (10 patients) in the placebo group compared with 10% (6 patients) in the tamsulosin group (p = 0.3161). Eighty-eight percent (14 patients) of those who developed urinary retention experienced it within 2 weeks after the PI. Intolerable urinary symptoms were reported equally (10 patients in each group) with 70% occurring in the first 2 weeks after PI. There was a significant difference in mean AUA score in favor of tamsulosin at Week 5 after PI (p = 0.03). Conclusions: Prophylactic tamsulosin (0.8 mg/day) before prostate brachytherapy did not significantly affect urinary retention rates, but had a positive effect on urinary morbidity at

  16. Onion peel extract reduces the percentage of body fat in overweight and obese subjects: a 12-week, randomized, double-blind, placebo-controlled study

    PubMed Central

    Lee, Ji-Sook; Cha, Yong-Jun; Lee, Kyung-Hea

    2016-01-01

    BACKGROUND/OBJECTIVES The anti-obesity effect of quercetin-rich onion peel extract (OPE) was suggested in rats, but information from human studies is limited. This study aimed to investigate the effects of OPE on the body composition of overweight and obese subjects. MATERIALS/METHODS In this 12-week, randomized, double-blind, placebo-controlled study, parallel clinical trials were performed in overweight and obese Korean subjects. Randomly assigned subjects were instructed to take daily either the placebo (male, 6 and female, 30) or OPE capsules containing 100 mg of quercetin (male, 5 and female, 31). Body composition was measured by using bioimpedance and dual-energy X-ray absorptiometry (DXA). Resting energy expenditure (REE) and respiratory quotient (RQ) were evaluated by using indirect calorie measurement methods. Fasting blood levels of glucose, insulin, lipids, and leptin were determined. RESULTS Quercetin-rich OPE supplementation significantly reduced the weight and percentage of body fat as measured by DXA (P = 0.02). These effects were not shown in the control group. Levels of blood glucose (P = 0.04) and leptin (P = 0.001 for placebo, P = 0.002 for OPE) decreased in both groups. Significant increases in REE and RQ were observed in both groups (P = 0.003 for placebo, P = 0.006 for OPE) and in the OPE group alone (P = 0.02), respectively. CONCLUSIONS Quercetin-rich OPE supplementation changed the body composition of the overweight and obese subjects. This result suggests a beneficial role of the anti-obesity effect of OPE human subjects. PMID:27087901

  17. Functional Dyspepsia Treatment Trial (FDTT): A double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics

    PubMed Central

    Talley, Nicholas J.; Locke, G. Richard; Herrick, Linda M.; Silvernail, Vickie M.; Prather, Charlene M.; Lacy, Brian E.; DiBaise, John K.; Howden, Colin W.; Brenner, Darren M.; Bouras, Ernest P.; El-Serag, Hashem B.; Abraham, Bincy P.; Moayyedi, Paul; Zinsmeister, Alan R.

    2014-01-01

    Background Functional dyspepsia (FD) is a common problem affecting up to 10–25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. Objectives The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. Design The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNβ3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. Methods The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651). PMID:22343090

  18. Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation

    PubMed Central

    Spiller, Robin; Pélerin, Fanny; Maudet, Corinne; Housez, Béatrice; Cazaubiel, Murielle; Jüsten, Peter

    2015-01-01

    Background Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and/or discomfort. Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear. Objective This study was designed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms. Methods A randomized, double blind, placebo-controlled trial has been performed in 379 subjects with diagnosed IBS. Subjects were randomly supplemented with the probiotics (1000 mg) or placebo for 12 weeks. Questionnaires (gastrointestinal symptoms, stools, wellbeing, and quality of life) were completed. Primary endpoint was percentage of responders defined as having a 50% decrease in the weekly average “intestinal pain/discomfort score” for at least 4 out of the last 8 weeks of the study. Results There was no overall benefit of S. cerevisiae I-3856 on IBS symptoms and wellbeing in the study population. Moreover, S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects (p > 0.05). Planned subgroup analyses showed significant effect in the IBS-C subjects: improvement of gastrointestinal symptoms was significantly higher in active group, compared to placebo, on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation. Conclusions In this study, S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients. However, it seems to have an effect in the subgroup with constipation which needs further studies to confirm (NCT01613456 in ClinicalTrials.gov registry). PMID:27403301

  19. Metformin intervention in obese non-diabetic patients with breast cancer: phase II randomized, double-blind, placebo-controlled trial.

    PubMed

    Ko, Kwang-Pil; Ma, Seung Hyun; Yang, Jae-Jeong; Hwang, Yunji; Ahn, Choonghyun; Cho, Young-Min; Noh, Dong-Young; Park, Byung-Joo; Han, Wonshik; Park, Sue K

    2015-09-01

    Previous observational studies have suggested that metformin in diabetes patients may reduce breast cancer risk more than the reductions from other anti-diabetes medications. This randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of metformin for controlling physical and metabolic profiles related to prognosis and adverse events in non-diabetic breast cancer patients. Female breast cancer patients (N = 105), at least 6 months post-mastectomy, with obesity (≥25 kg/m(2)) and/or pre-diabetes (fasting blood sugar levels ≥100 mg/dL), were randomly assigned to three groups (placebo, metformin 500 mg, and metformin 1000 mg) stratified by tamoxifen use. A linear mixed model for repeated measurements among three groups and ANOVA for profile differences during 6 months of treatment were used for the intention-to-treat analysis. The metformin 1000 mg group had a significantly greater decline in glucose and HbA1c levels between treatment weeks 0 and 6 month (p = 0.008 and 0.009, respectively), and the declines increased with an increase in body mass index (BMI) level (p interaction with BMI = 0.007 and 0.067, respectively). A marginally significant different effect from the metformin 1000 mg treatment was detected for glucose and HbA1c levels (p interaction = 0.084 and 0.063, respectively) in the intention-to-treat analysis. Metformin 1000 mg treatment had a favorable effect on controlling glucose and HbA1C levels in obese non-diabetic breast cancer patients, indicating prognostic importance. Further trials are needed to elucidate the risk-benefit ratio of long-term use of metformin. PMID:26293146

  20. Homeopathic medicine for acute cough in upper respiratory tract infections and acute bronchitis: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Zanasi, Alessandro; Mazzolini, Massimiliano; Tursi, Francesco; Morselli-Labate, Antonio Maria; Paccapelo, Alexandro; Lecchi, Marzia

    2014-02-01

    Cough is a frequent symptom associated to upper respiratory tract infections (URTIs) and, although being self-limiting, it might deeply affect the quality of life. Homeopathic products are often employed by patients to treat cough, but the evidence on their efficacy is scarce. Thus, we tested the efficacy of a homeopathic syrup in treating cough arising from URTIs with a randomized, double blind, placebo controlled clinical trial. Patients were treated with either the homeopathic syrup or a placebo for a week, and recorded cough severity in a diary by means of a verbal category-descriptive score for two weeks. Sputum viscosity was assessed with a viscosimeter before and after 4 days of treatment; patients were also asked to provide a subjective evaluation of viscosity. Eighty patients were randomized to receive placebo (n = 40) or the homeopathic syrup (n = 40). All patients completed the study. In each group cough scores decreased over time, however, after 4 and 7 days of treatment, cough severity was significantly lower in the homeopathic group than in the placebo one (p < 0.001 and p = 0.023, respectively). Sputum was collected from 53 patients: in both groups its viscosity significantly decreased after 4 days of treatment (p < 0.001); however, viscosity was significantly lower in the homeopathic group (p = 0.018). Instead, the subjective evaluation did not significantly differ between the two groups (p = 0.059). No adverse events related to any treatment were reported. We concluded that the homeopathic syrup employed in the study was able to effectively reduce cough severity and sputum viscosity, thereby representing a valid remedy for the management of acute cough induced by URTIs.

  1. A randomized, placebo-controlled, double-blind trial on the management of post-infective cough by inhaled ipratropium and salbutamol administered in combination.

    PubMed

    Zanasi, Alessandro; Lecchi, Marzia; Del Forno, Manuela; Fabbri, Elisa; Mastroroberto, Marianna; Mazzolini, Massimiliano; Pisani, Lara; Pandolfi, Paolo; Nava, Stefano; Morselli-Labate, Antonio Maria

    2014-12-01

    Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a β-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a β-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.

  2. Improvement of skin condition by oral supplementation with sphingomyelin-containing milk phospholipids in a double-blind, placebo-controlled, randomized trial.

    PubMed

    Higurashi, S; Haruta-Ono, Y; Urazono, H; Kobayashi, T; Kadooka, Y

    2015-10-01

    Sphingomyelin (SM), an essential phospholipid for the skin, is contained largely in the milk fat globule membrane surrounding milk fat, concentrated fractions of which are also generated concurrently during the manufacture of dairy products. Such an SM-containing milk phospholipid concentrate (SM-MPC) is useful for investigating the benefits of dietary SM. Here, we examined the effect of consuming SM-MPC on the condition of skin in a double-blind, placebo-controlled, randomized trial. Ninety-six healthy subjects aged 20 to 39 yr with low skin hydration were randomly assigned to 3 groups: a high-SM group supplemented with SM-MPC at a dose equivalent to 10 mg/d of SM, a low-SM group supplemented with SM-MPC equivalent to 5 mg/d of SM, and a placebo group fed a vehicle composed of olive oil and beeswax. During daily supplementation for 12 wk, parameters related to the condition of skin were evaluated at baseline and every 3 wk. Skin hydration at the heel was significantly increased at wk 9 and 12 in the low-SM group compared with the placebo group. Skin elasticity in the region below the eye was significantly increased at wk 9 in the high-SM group versus placebo. Questionnaire-based subjective perceptions of skin conditions were significantly improved for facial skin moisture at wk 3 and 12, and in the wrinkle around the eyes at wk 9 and 12 in the high-SM group versus placebo. Our results indicate that constant and long-term supplementation with SM-MPC is capable of improving the general condition of skin. PMID:26277314

  3. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Hansen, Melissa V; Andersen, Lærke T; Madsen, Michael T; Hageman, Ida; Rasmussen, Lars S; Bokmand, Susanne; Rosenberg, Jacob; Gögenur, Ismail

    2014-06-01

    Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30-75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077-0.80]), giving a NNT of 3.0 [95 % CI 1.7-11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery. PMID:24756186

  4. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial.

    PubMed

    Bo, S; Ponzo, V; Ciccone, G; Evangelista, A; Saba, F; Goitre, I; Procopio, M; Pagano, G F; Cassader, M; Gambino, R

    2016-09-01

    The polyphenol resveratrol is considered to exert many beneficial actions, such as antioxidant, anti-inflammatory, insulin-sensitizer and anticancer effects. Its benefits in patients with type 2 diabetes mellitus (T2DM) are controversial. Our aims were to determine whether resveratrol supplementation at two different dosages (500 and 40mg/day) for 6 months i) reduced the concentrations of C-reactive-protein (CRP) and ii) ameliorated the metabolic pattern of T2DM patients. In the present double-blind, randomized, placebo-controlled trial, 192 T2DM patients were randomized to receive resveratrol 500mg/day (Resv500arm), resveratrol 40mg/day (Resv40arm) or placebo for 6-months. At baseline and at the trial end, CRP values, anthropometric, metabolic and liver parameters were determined. No serious adverse event occurred. A dose-dependent, though not significant, CRP decrease of 5.6% (Resv40arm) and 15.9% (Resv500arm) was observed vs placebo. We failed to detect significant differences in weight, BMI, waist circumference, and values of arterial blood pressure, fasting glucose, glycated hemoglobin, insulin, C-peptide, free fatty acids, liver transaminases, uric acid, adiponectin, interleukin-6, in both the Resv500 and Resv40 arms vs placebo. Total cholesterol and triglycerides slightly increased in the Resv500arm. Subgroup analyses revealed that lower diabetes duration (in both Resv500 and Resv40arms), and, in the Resv500arm, younger age, aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo. The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations, nor improve the metabolic pattern of T2DM patients. PMID:27520400

  5. Effect of Vitamin C Supplementation on C-reactive Protein Levels in Patients Undergoing Hemodialysis: A Randomized, Double Blind, Placebo-Controlled Study

    PubMed Central

    Biniaz, Vajihe; Sadeghi Shermeh, Mehdi; Ebadi, Abbas; Tayebi, Ali; Einollahi, Behzad

    2013-01-01

    Background: Chronic inflammation is the most important cause of cardiovascular disease in patients undergoing hemodialysis, and vitamin C as a major antioxidant which could be effective to suppress inflammation. Objectives: This study was performed to evaluate the effect of vitamin C supplementation on C-reactive protein levels in patients undergoing hemodialysis. Patients and Methods: This randomized, placebo-controlled and double-blind trial was conducted on 151 patients on hemodialysis who were divided randomly by lottery method to three identical groups. In the intervention group, 250 mg of vitamin C was injected intravenously immediately at the end of each hemodialysis session three times a week for 8 weeks in a row. In the control group 1, same term of placebo saline was injected, and in the control group 2, no intervention was performed. Results: A total of 86 (61%) male and 55 female patients with mean hemodialysis duration of 39.74 ± 45.5 months, and a mean age of 61.36 ± 11.46 years-old, participated in this study. Hypertension and diabetes were the most common underlying diseases (79.4%). Median baseline CRP in the intervention, control 1 and control 2 groups were 16.8, 17.8, and 19.4 mg/L respectively. After 2 months, median CRP reduced significantly in the vitamin C group to 10.7 (P = 0.04) vs. 22.6, and 30.6 mg/L in control groups. Conclusions: Our findings demonstrated that vitamin C supplementation modifies the levels of CRP in patients on hemodialysis. PMID:24719806

  6. Randomized, double-blind, placebo-controlled superiority trial of the Yiqigubiao pill for the treatment of patients with chronic obstructive pulmonary disease at a stable stage

    PubMed Central

    Li, Feng-Sen; Zhang, Yan-Li; Li, Zheng; Xu, Dan; Liao, Chun-Yan; Ma, Huan; Gong, Li; Su, Jun; Sun, Qi; Xu, Qian; Gao, Zhen; Wang, Ling; Jing, Jing; Wang, Jing; Jiang, Min; Tian, Ge; Hasan, Bilal

    2016-01-01

    In traditional Chinese medicine (TCM), the Yiqigubiao pill is commonly used to enhance physical fitness. The current clinical trial was designed to evaluate the efficacy and safety of the Yiqigubiao pill as an adjuvant therapy for patients with stable chronic obstructive pulmonary disease (COPD). The current trial was a randomized, double-blind, placebo-controlled superiority trial. The participants were recruited from outpatients at the Traditional Chinese Medicine Hospital affiliated with Xinjiang Medical University (Ürümqi, China) between February and September 2012. All participants were patients with stable COPD that were randomized to the Yiqigubiao pill (YQGB; n=84) or placebo (Pb; n=87) groups. The occurrences of acute exacerbation (AE) of COPD during the trial were recorded. Lung function value assessments, scoring of life quality and exercise endurance, arterial blood gas analysis and serum inflammatory cytokines level determination were performed prior to and throughout the study. A total of 139 participants completed the intervention and 132 participants completed the study. The interval between the initial intervention and the first AECOPD was greater in the YQGB group compared with the Pb group (P<0.01). The incidence rate of AECOPD was lower in the YQGB group than in the Pb group (P<0.01). Subsequent to the intervention or at the end of the study, the 6-min walking distance difference was longer in the YQGB group compared with the Pb group (P<0.01). The scores reflecting life quality decline became lower in the YQGB group (P<0.01). The serum levels of proinflammatory factors were downregulated to a greater extent in the YQGB group compared with the Pb group. Thus, the Yiqigubiao pill is an efficient and safe adjuvant therapy for the treatment of stable patients with COPD.

  7. Randomized, double-blind, placebo-controlled superiority trial of the Yiqigubiao pill for the treatment of patients with chronic obstructive pulmonary disease at a stable stage

    PubMed Central

    Li, Feng-Sen; Zhang, Yan-Li; Li, Zheng; Xu, Dan; Liao, Chun-Yan; Ma, Huan; Gong, Li; Su, Jun; Sun, Qi; Xu, Qian; Gao, Zhen; Wang, Ling; Jing, Jing; Wang, Jing; Jiang, Min; Tian, Ge; Hasan, Bilal

    2016-01-01

    In traditional Chinese medicine (TCM), the Yiqigubiao pill is commonly used to enhance physical fitness. The current clinical trial was designed to evaluate the efficacy and safety of the Yiqigubiao pill as an adjuvant therapy for patients with stable chronic obstructive pulmonary disease (COPD). The current trial was a randomized, double-blind, placebo-controlled superiority trial. The participants were recruited from outpatients at the Traditional Chinese Medicine Hospital affiliated with Xinjiang Medical University (Ürümqi, China) between February and September 2012. All participants were patients with stable COPD that were randomized to the Yiqigubiao pill (YQGB; n=84) or placebo (Pb; n=87) groups. The occurrences of acute exacerbation (AE) of COPD during the trial were recorded. Lung function value assessments, scoring of life quality and exercise endurance, arterial blood gas analysis and serum inflammatory cytokines level determination were performed prior to and throughout the study. A total of 139 participants completed the intervention and 132 participants completed the study. The interval between the initial intervention and the first AECOPD was greater in the YQGB group compared with the Pb group (P<0.01). The incidence rate of AECOPD was lower in the YQGB group than in the Pb group (P<0.01). Subsequent to the intervention or at the end of the study, the 6-min walking distance difference was longer in the YQGB group compared with the Pb group (P<0.01). The scores reflecting life quality decline became lower in the YQGB group (P<0.01). The serum levels of proinflammatory factors were downregulated to a greater extent in the YQGB group compared with the Pb group. Thus, the Yiqigubiao pill is an efficient and safe adjuvant therapy for the treatment of stable patients with COPD. PMID:27698749

  8. 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

    PubMed Central

    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

  9. Minoxidil 2% lotion for eyebrow enhancement: a randomized, double-blind, placebo-controlled, spilt-face comparative study.

    PubMed

    Lee, Saridpong; Tanglertsampan, Chuchai; Tanchotikul, Mingkwan; Worapunpong, Nigun

    2014-02-01

    Topical minoxidil has been successfully used to treat androgenetic alopecia. It can also be applied to enhance eyebrows. However, there is no study comparing minoxidil lotion with placebo for eyebrow enhancement. In this trial, we determined the efficacy and safety of minoxidil 2% lotion for eyebrow enhancement compared with placebo. Forty patients were randomized for minoxidil on the eyebrow on one side of the face and placebo on the other. Efficacy was evaluated by global photographic assessment, eyebrow diameter, eyebrow count and subject's satisfaction. Side-effects were also evaluated. Thirty-nine patients (97.5%) completed the study. After 16 weeks, the minoxidil group achieved significantly better results in all measured outcomes compared to the placebo group. Side-effects were minor and did not preclude patients from continuing the study. Our study suggests that minoxidil 2% lotion is a safe and effective treatment for eyebrow hypotrichosis. PMID:24471459

  10. Minoxidil 2% lotion for eyebrow enhancement: a randomized, double-blind, placebo-controlled, spilt-face comparative study.

    PubMed

    Lee, Saridpong; Tanglertsampan, Chuchai; Tanchotikul, Mingkwan; Worapunpong, Nigun

    2014-02-01

    Topical minoxidil has been successfully used to treat androgenetic alopecia. It can also be applied to enhance eyebrows. However, there is no study comparing minoxidil lotion with placebo for eyebrow enhancement. In this trial, we determined the efficacy and safety of minoxidil 2% lotion for eyebrow enhancement compared with placebo. Forty patients were randomized for minoxidil on the eyebrow on one side of the face and placebo on the other. Efficacy was evaluated by global photographic assessment, eyebrow diameter, eyebrow count and subject's satisfaction. Side-effects were also evaluated. Thirty-nine patients (97.5%) completed the study. After 16 weeks, the minoxidil group achieved significantly better results in all measured outcomes compared to the placebo group. Side-effects were minor and did not preclude patients from continuing the study. Our study suggests that minoxidil 2% lotion is a safe and effective treatment for eyebrow hypotrichosis.

  11. Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: A randomized, double-blind, placebo-controlled, stratified, parallel-grouptrial

    PubMed Central

    Raine, Adrian; Portnoy, Jill; Liu, Jianghong; Mahoomed, Tashneem; Hibbeln, Joseph

    2014-01-01

    Background While limited evidence suggests that omega-3 supplementation may reduceantisocial behavior in children, studies have not reported on post-treatment follow-up and most treatment periods have been of short duration. This study tests the hypothesis that omega-3 supplementation over six months will reduce behavior problems in children both at the end of treatment and at six months post-treatment. Methods In this randomized, double-blind, placebo-controlled, stratified, parallel group trial, a community sample of 8-16 year old children were randomized into a treatment group (N = 100) and a placebo-control group (N = 100). The supplementation consisted of a fruit drink containing 1 gram/day of omega-3 or a placebo consisting of the same fruit drink without omega-3. Participants, care-givers, and research assistants were blinded to group assignment. The primary outcome measures of externalizing and internalizing behavior problems were reported by both caregivers and their children in a laboratory setting at 0 months (baseline), 6 months (end of treatment) and 12 months (6 months post-treatment), together with the secondary outcome measures of parental antisocial behavior. Data were analyzed on an intention-to-treat basis including all participants. Results Significant group × time interactions were observed with the treatment group showing long-term improvements in child behavior problems. The average post-treatment effect size was d = -.59. Effects were documented for parent-reports, but with theexception of proactive and reactive aggression,child-report data were non-significant.Parents whose children took omega-3showed significant post-treatment reductions in their own antisocial and aggressive behavior.Thisimprovementin caregiver behavior partly mediated the improvements observed in child behavior. Conclusions Findings provide initialevidence that omega-3 supplementation can produce sustained reductions in externalizing andinternalizing behavior problems

  12. Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

    PubMed

    Diamond, Michael P; Carr, Bruce; Dmowski, W Paul; Koltun, William; O'Brien, Chris; Jiang, Ping; Burke, Joshua; Jimenez, Roland; Garner, Elizabeth; Chwalisz, Kristof

    2014-03-01

    This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

  13. S-ADENOSYLMETHIONINE TREATMENT OF ALCOHOLIC LIVER DISEASE: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

    PubMed Central

    Medici, Valentina; Virata, Maria Catrina; Peerson, Janet M.; Stabler, Sally P.; French, Samuel W.; Gregory, Jesse F.; Albanese, Anthony; Bowlus, Christopher L.; Devaraj, Sridevi; Panacek, Edward A.; Richards, John R.; Halsted, Charles H.

    2011-01-01

    Background S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione (GSH), the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALD). The aim of this study was to determine the efficacy of SAM in treatment of ALD in a 24 week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoint was changes in serum levels of methionine metabolites. Methods We randomized 37 patients with ALD to receive 1.2 grams of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects and a post-treatment liver biopsy was performed in 14 subjects. Results Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies. Conclusions Whereas abstinence improved liver function, twenty-four weeks of therapy with SAM was no more effective than placebo in the treatment of ALD. PMID:22044287

  14. Microbial cell preparation in enteral feeding in critically ill patients: A randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Malik, Ausama A; Rajandram, Retnagowri; Tah, Pei Chien; Hakumat-Rai, Vineya-Rai; Chin, Kin-Fah

    2016-04-01

    Gut failure is a common condition in critically ill patients in the intensive care unit (ICU). Enteral feeding is usually the first line of choice for nutrition support in critically ill patients. However, enteral feeding has its own set of complications such as alterations in gut transit time and composition of gut eco-culture. The primary aim of this study was to investigate the effect of microbial cell preparation on the return of gut function, white blood cell count, C-reactive protein levels, number of days on mechanical ventilation, and length of stay in ICU. A consecutive cohort of 60 patients admitted to the ICU in University Malaya Medical Centre requiring enteral feeding were prospectively randomized to receive either treatment (n = 30) or placebo (n = 30). Patients receiving enteral feeding supplemented with a course of treatment achieved a faster return of gut function and required shorter duration of mechanical ventilation and shorter length of stay in the ICU. However, inflammatory markers did not show any significant change in the pretreatment and posttreatment groups. Overall, it can be concluded that microbial cell preparation enhances gut function and the overall clinical outcome of critically ill patients receiving enteral feeding in the ICU.

  15. A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders

    PubMed Central

    2013-01-01

    Background This study examined the efficacy and safety of N-acetylcysteine (NAC) augmentation for treating irritability in children and adolescents with autism spectrum disorders (ASD). Method Forty children and adolescents met diagnostic criteria for ASD according to DSM-IV. They were randomly allocated into one of the two groups of NAC (1200 mg/day)+risperidone or placebo+risperidone. NAC and placebo were administered in the form of effervescent and in two divided doses for 8 weeks. Irritability subscale score of Aberrant Behavior Checklist (ABC) was considered as the main outcome measure. Adverse effects were also checked. Results The mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. Repeated measures of ANOVA showed that there was a significant difference between the two groups after 8 weeks. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect. Conclusions Risperidone plus NAC more than risperidone plus placebo decreased irritability in children and adolescents with ASD. Meanwhile, it did not change the core symptoms of autism. Adverse effects were not common and NAC was generally tolerated well. Trial registration This trial was registered at http://www.irct.ir. The registration number of this trial was IRCT201106103930N6 PMID:23886027

  16. Efficacy of Korean Red Ginseng by Single Nucleotide Polymorphism in Obese Women: Randomized, Double-blind, Placebo-controlled Trial

    PubMed Central

    Kwon, Dong Hyun; Bose, Shambhunath; Song, Mi Young; Lee, Myeong Jong; Lim, Chi Yeon; Kwon, Bum Sun; Kim, Ho Jun

    2012-01-01

    This study examined the effects of Korean red ginseng (KRG) on obese women and aimed to confirm that the effects of KRG on obesity differ dependently on a gene. Fifty obese women were recruited and randomized to receive KRG (n=24) or placebo (n=26) for 8 wk. Measurements of blood pressure, height, weight, waist circumference, waist-hip ratio (WHR), total fat mass, percentage of body fat, resting metabolic rate, basal body temperature, and daily food intake (FI), blood test (serum lipid, liver and renal function), Korean version of obesity-related quality of life scale (KOQOL), and a gene examination were performed. Comparisons of subjects before and after the administration of KRG revealed significant improvements of obesity in terms of weight, body mass index (BMI), WHR, FI, and KOQOL. However, in the comparison between KRG group and placebo group, only KOQOL was significantly different. KRG displayed significant efficacy on BMI and KOQOL in the CT genotype of the G protein beta 3 gene, but not in the CC genotype, on blood sugar test in the Trp64/Arg genotype of the beta 3 adrenergic receptor gene, but not in Trp64/ Trp genotype, on KOQOL in the DD genotype of the angiotensin I converting enzyme gene, but not in the ID and DD genotypes. The effects of KRG on obesity were confirmed to some extent. However, a distinct effect compared to placebo was not confirmed. KRG is more effective for improving the secondary issues of the quality of life derived from obesity rather than having direct effects on the obesity-related anthropometric assessment and blood test indices. PMID:23717118

  17. Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Fornaro, Michele; Martino, Matteo; Mattei, Chiara; Prestia, Davide; Vinciguerra, Valentina; De Berardis, Domenico; De Pasquale, Concetta; Iasevoli, Felice; Mungo, Sergio; Fornaro, Pantaleo

    2014-08-01

    The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=0.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=0.028] non-responder cases in the "+placebo" and "+bupropion" groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features.

  18. Effects of Pentoxifylline on Non-Alcoholic Steatohepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial in Iran

    PubMed Central

    Baniasadi, Nadieh; Salajegheh, Faranak; Pardakhty, Abbas; Seyedmirzaee, Seyed Mehdi; Hayatbakhsh, Mohammad Mahdi; Nikpoor, Amin Reza; Mohammadi, Mojgan

    2015-01-01

    Background: Non-alcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease. Several studies suggest that pentoxifylline (PTX) can improve the disease outcome. Objectives: We aimed to compare the effect of pentoxifylline with placebo on liver aminotransferases and cytokines, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 8 (IL-8) in patients with NASH. Patients and Methods: Thirty patients with NASH were included in the study, based on ultrasonography and 1.5-fold mean change from baseline serum levels of liver aminotransferases. Patients with NASH were randomized to receive 1200 mg PTX (the intervention group) or placebo (the placebo group) for 6 months. The serum levels of liver aminotransferases and cytokines were compared between the intervention and placebo groups, at various time points. Results: The serum levels of liver aminotransferases were significantly reduced at 3 months and at 6 months, compared with baseline, in both groups. The serum levels of IL-6 were significantly decreased, in both groups, only at 6 months, compared with baseline. Compared to the placebo group, the serum level of TNF-α was significantly decreased in the intervention group, at 6 months. The serum level of IL-8 was increased, in both groups, after 6 months, without reaching clinical significance. There was no significant difference in serum levels of liver aminotransferases and cytokines, between intervention and placebo groups. Conclusions: Decreases in the serum levels of liver aminotransferases and cytokines, in both groups, are related to low-calorie diets and exercise, rather than PTX. PMID:26834792

  19. Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Yang, Yi-Sun; Su, Ying-Fang; Yang, Hui-Wen; Lee, Yu-Hsien; Chou, Janet I; Ueng, Kwo-Chang

    2014-12-01

    Human studies of curcumin extract on lipid-lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty-five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high-density lipoprotein cholesterol (HDL-C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low-density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The triglyceride-lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL-C effect in female patients, both of which result in a decrease of T-Chol/HDL-C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid-lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol-related parameters, especially in metabolic syndrome patients.

  20. Duloxetine-bupropion combination for treatment-resistant atypical depression: a double-blind, randomized, placebo-controlled trial.

    PubMed

    Fornaro, Michele; Martino, Matteo; Mattei, Chiara; Prestia, Davide; Vinciguerra, Valentina; De Berardis, Domenico; De Pasquale, Concetta; Iasevoli, Felice; Mungo, Sergio; Fornaro, Pantaleo

    2014-08-01

    The efficacy, safety, and tolerability of combined bupropion versus placebo using duloxetine as active reference drug, in patients with a DSM-IV diagnosis of major depression with atypical features and a history of treatment resistance, were evaluated in this preliminary six-week study. Patients (n=46) had a baseline Hamilton Depression Scale (HAM-D) ≥14 and were randomly assigned to 150/300 mg/day bupropion vs. placebo, which was added to 60 to 120 mg/day duloxetine depending on baseline depression severity. Atypical features of depression were assessed using the additional eight-item module of the Structured Interview Guide for the HAM-D with the Atypical Depression Supplement. By week 6, only five (21.7%) patients receiving duloxetine+placebo vs. six (26.1%) patients on the bupropion combination achieved response. No significant difference in final HAM-D scores between the two groups was observed between those patients achieving response. The presence of a higher number of atypical features significantly predicted non-response, with the relevant binary logistic regression model correctly classifying 17 out 22 (77.3%) of non-responders [Exp(B)=0.294; p=0.016] vs. 17 out 23 (73.9%) [Exp(B)=0.353; p=0.028] non-responder cases in the "+placebo" and "+bupropion" groups, respectively. In those patients receiving bupropion, treatment-emergent adverse events leading to withdrawal were more common among those receiving lower doses of the combination drug, and no life-threating dangers were noted. Additional studies, including an adequate course of duloxetine trial, are nonetheless aimed to allow a firm conclusion about the usefulness of the combination of duloxetine and bupropion for treatment-resistant cases of major depression with atypical features. PMID:24842649

  1. A Phase 1 Randomized, Double Blind, Placebo Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (MTN-007)

    PubMed Central

    Mcgowan, Ian; Hoesley, Craig; Cranston, Ross D.; Andrew, Philip; Janocko, Laura; Dai, James Y.; Carballo-Dieguez, Alex; Ayudhya, Ratiya Kunjara Na; Piper, Jeanna; Hladik, Florian; Mayer, Ken

    2013-01-01

    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. PMID:23573238

  2. Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus.

    PubMed

    Joe, Andrew K; Schnoll-Sussman, Felice; Bresalier, Robert S; Abrams, Julian A; Hibshoosh, Hanina; Cheung, Ken; Friedman, Richard A; Yang, Chung S; Milne, Ginger L; Liu, Diane D; Lee, J Jack; Abdul, Kazeem; Bigg, Michelle; Foreman, Jessica; Su, Tao; Wang, Xiaomei; Ahmed, Aqeel; Neugut, Alfred I; Akpa, Esther; Lippman, Scott M; Perloff, Marjorie; Brown, Powel H; Lightdale, Charles J

    2015-12-01

    This study was conducted to determine the safety and efficacy of the green tea-derived Polyphenon E (Poly E) in patients with Barrett's Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E-treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level--mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa. PMID:26471236

  3. Beneficial effects of dark chocolate on exercise capacity in sedentary subjects: underlying mechanisms. A double blind, randomized, placebo controlled trial.

    PubMed

    Taub, Pam R; Ramirez-Sanchez, Israel; Patel, Minal; Higginbotham, Erin; Moreno-Ulloa, Aldo; Román-Pintos, Luis Miguel; Phillips, Paul; Perkins, Guy; Ceballos, Guillermo; Villarreal, Francisco

    2016-09-14

    In heart failure patients the consumption of (-)-epicatechin ((-)-Epi)-rich cocoa can restore skeletal muscle (SkM) mitochondrial structure and decrease biomarkers of oxidative stress. However, nothing is known about its effects on exercise capacity and underlying mechanisms in normal, sedentary subjects. Twenty normal, sedentary subjects (∼50 years old) were randomized to placebo or dark chocolate (DC) groups and consumed 20 g of the products for 3 months. Subjects underwent before and after treatment, bicycle ergometry to assess VO2 max and work, SkM biopsy to assess changes in mitochondrial density, function and oxidative stress and blood sampling to assess metabolic endpoints. Seventeen subjects completed the trial. In the DC group (n = 9), VO2 max increased (17% increase, p = 0.056) as well as maximum work (watts) achieved (p = 0.026) with no changes with placebo (n = 8). The DC group evidenced increases in HDL levels (p = 0.005) and decreased triglycerides (p = 0.07). With DC, SkM evidenced significant increases in protein levels for LKB1, AMPK and PGC1α and in their active forms (phosphorylated AMPK and LKB1) as well as in citrate synthase activity while no changes were observed in mitochondrial density. With DC, significant increases in SkM reduced glutathione levels and decreases in protein carbonylation were observed. Improvements in maximum work achieved and VO2 max may be due to DC activation of upstream control systems and enhancement of SkM mitochondria efficiency. Larger clinical studies are warranted to confirm these observations. PMID:27491778

  4. Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Greenspan, Susan L.; Brufsky, Adam; Lembersky, Barry C.; Bhattacharya, Rajib; Vujevich, Karen T.; Perera, Subashan; Sereika, Susan M.; Vogel, Victor G.

    2014-01-01

    Purpose Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer–related bone loss in this cohort. Patients and Methods Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. Results At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean ± SE) 4.8% ± 0.8% at the spine and 2.8% ± 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% ± 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% ± 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% ± 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups. Conclusion We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated. PMID:18427147

  5. Intravenous Ibuprofen for Treatment of Post-Operative Pain: A Multicenter, Double Blind, Placebo-Controlled, Randomized Clinical Trial

    PubMed Central

    Escontrela Rodriguez, Blanca; Planas Roca, Antonio; Martínez Ruiz, Alberto

    2016-01-01

    Background Non-steroidal anti-inflammatory drugs are often used as components of multimodal therapy for postoperative pain management, but their use is currently limited by its side effects. The specific objective of this study was to evaluate the efficacy and safety of a new formulation of intravenous (IV) ibuprofen for the management of postoperative pain in a European population. Methods and Findings A total of 206 patients from both abdominal and orthopedic surgery, were randomly assigned in 1:1 ratio to receive 800 mg IV-ibuprofen or placebo every 6 hours; all patients had morphine access through a patient controlled analgesia pump. The primary outcome measure was median morphine consumption within the first 24 hours following surgery. The mean±SEM of morphine requirements was reduced from 29,8±5,25 mg to 14,22±3,23 mg (p = 0,015) and resulted in a decrease in pain at rest (p = 0,02) measured by Visual Analog Scale (VAS) from mean±SEM 3.34±0,35 to 0.86±0.24, and also in pain during movement (p = 0,02) from 4.32±0,36 to 1.90±0,30 in the ibuprofen treatment arm; while in the placebo group VAS score at rest ranged from 4.68±0,40 to 2.12±0,42 and during movement from 5.66±0,42 to 3.38±0,44. Similar treatment-emergent adverse events occurred across both study groups and there was no difference in the overall incidence of these events. Conclusions Perioperative administration of IV-Ibuprofen 800 mg every 6 hours in abdominal surgery patient’s decreases morphine requirements and pain score. Furthermore IV-Ibuprofen was safe and well tolerate. Consequently we consider appropriate that protocols for management of postoperative pain include IV-Ibuprofen 800 mg every 6 hours as an option to offer patients an analgesic benefit while reducing the potentially risks associated with morphine consumption. Trial Registration EU Clinical Trials Register 2011-005007-33 PMID:27152748

  6. Comparison of oral montelukast with oral zileuton in acute asthma: A randomized, double-blind, placebo-controlled study

    PubMed Central

    Magazine, Rahul; Shahul, Hameed Aboobackar; Chogtu, Bharti; Kamath, Asha

    2016-01-01

    Background: Leukotriene modifiers have an established role in the management of chronic asthma but their role in acute asthma is still under evaluation. Objective: To study and compare the effects of oral montelukast with oral zileuton in acute asthma. Materials and Methods: This study included 120 asthmatics and was conducted from September 2012 to March 2014. Patients were randomized into three different groups to receive montelukast or zileuton or placebo in addition to standard treatment for asthma exacerbation. Peak expiratory flow rate (PEFR) values, details of rescue medication and vital signs were recorded at 6 h, 12 h, 24 h, and 48 h of drug or placebo administration and at discharge. Additional recording was done in the morning (8–10 am) following admission. The primary endpoint was the mean PEFR of each group at these time points; the secondary end point being the need for rescue medications. Results: The mean PEFR recordings of the three study groups – placebo, montelukast, and zileuton – respectively, at various time points were as follows: at 6 h (223.25 ± 90.40, 199.00 ± 82.52, 233.75 ± 84.05; P = 0.240); at 12 h (271.00 ± 109.38, 251.50 ± 101.44, 309.50 ± 129.63; P = 0.048); at 24 h (288.25 ± 114.26, 269.00 ± 107.51, 324.50 ± 127.88; P = 0.080); and at 48 h (295.00 ± 114.80, 293.50 ± 113.24, 344.75 ± 119.91; P = 0.015); discharge (305.00 ± 118.56, 305.25 ± 119.51, 361.25 ± 119.70; P = 0.010). The mean PEFR for the three study groups at 8–10 am on the morning following admission was 268.75 ± 111.43, 252.50 ± 99.99, 306.75 ± 114.44; P = 0.047. Total rescue doses needed were 10, 1, and 0, respectively (P = 0.049). Conclusion: Zileuton is better than montelukast as an additional drug in acute asthma and results in significant improvement in lung function, and reduction in the need for rescue medications. PMID:27185992

  7. Butorphanol suppresses fentanyl-induced cough during general anesthesia induction: A randomized, double-blinded, placebo-controlled clinical trial.

    PubMed

    Cheng, Xiao-Yan; Lun, Xiao-Qin; Li, Hong-Bo; Zhang, Zhi-Jie

    2016-06-01

    Fentanyl-induced cough (FIC) is unwanted in the patients requiring stable induction of general anesthesia. This study was designed to evaluate the suppressive effects of butorphanol pretreatment on the incidence and severity of FIC during the induction of general anesthesia. A total of 315 patients of American Society of Anesthesiologists physical status I and II, scheduled for elective surgery under general anesthesia were randomized into 3 equally sized groups (n = 0105). Two minutes before fentanyl bolus, group I received intravenously 5 mL normal saline, groups II and III received butorphanol 0.015 and 0.03 mg/kg (diluted with saline to 5 mL), respectively. Patients were then administrated with fentanyl 2.5 μg/kg within 5 s. The incidence and severity of FIC was recorded for 2 minutes after fentanyl bolus. During experimental period, the mean arterial pressure, heart rate, and peripheral capillary oxygen saturation (SpO2) were recorded before the administration of butorphanol or normal saline (T0), 2 minutes (T1) after butorphanol injection, and 2 minutes (T2) after fentanyl injection. The incidence of FIC was 31.4% in group I, 11.4% in group II, and 3.8% in group III. Group III had a lowest incidence of FIC among 3 groups (P < 0.001, vs group I; P < 0.05, vs group II). The severe FIC was not observed in groups II and III, but was recoded from 6 patients in group I. At 2 minutes after fentanyl injection (T2), the mean arterial pressure was significantly higher in group I than that in groups II and III (P < 0.01, vs group II; P < 0.05, vs group III), but the values remained within safe limits. In conclusion, pretreatment with butorphanol could effectively and safely suppress FIC during anesthesia induction. PMID:27367987

  8. Efficacy of micronutrient supplementation on skin aging and seasonal variation: a randomized, placebo-controlled, double-blind study

    PubMed Central

    Fanian, Ferial; Mac-Mary, Sophie; Jeudy, Adeline; Lihoreau, Thomas; Messikh, Rafat; Ortonne, Jean-Paul; Sainthillier, Jean-Marie; Elkhyat, Ahmed; Guichard, Alexandre; Kenari, Kamran Hejazi; Humbert, Philippe

    2013-01-01

    Background Several studies have confirmed dramatic changes in skin surface parameters during the winter months. Although there are many studies supporting the positive effects of topical treatment, there are no published studies demonstrating the effects of oral supplementation in the prevention of negative skin changes during winter. The purpose of this study was to evaluate the efficacy of an oral micronutrient supplement in preventing the negative effects of winter weather on skin quality using noninvasive biometrologic instruments. Methods This study included 80 healthy female volunteers aged 35–55 years with phototype II–IV skin. Randomization was balanced. Two tablets of a micronutrient supplement (Perfectil® Platinum) or placebo were administered once daily for 4 months. The volunteers were examined at baseline, after 4 months, and 6 weeks after termination of treatment (month 5.5). The evaluation included skin microrelief by Visioscan® as the main outcome, and the secondary outcomes were results on standard macrophotography, skin tension by Reviscometer®, skin high-frequency ultrasound, and self-assessment. Results For all pseudoroughness and microrelief indicators, there was a significant increase from baseline to month 4 in the placebo group (P<0.05) but no change in the active group. Descriptive statistics for the mean minimum, mean maximum, and minimum to maximum ratio on the nonexposed study zone showed a significant and dramatic difference between baseline and month 4 and between baseline and month 5.5 (P<0.05) in the active group, indicating decreasing anisotropy of the skin. High-frequency ultrasound on the exposed study zone revealed that skin thickness was significantly decreased in the placebo group during winter but was stable in the treated group (P<0.01). The photography scaling and self-assessment questionnaire revealed no significant changes in either group. Conclusion These results indicate that the skin is prone to seasonal changes

  9. Patient-Provider Interactions Affect Symptoms in Gastroesophageal Reflux Disease: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Dossett, Michelle L.; Mu, Lin; Davis, Roger B.; Bell, Iris R.; Lembo, Anthony J.; Kaptchuk, Ted J.; Yeh, Gloria Y.

    2015-01-01

    Background It is unclear whether the benefits that some patients derive from complementary and integrative medicine (CIM) are related to the therapies recommended or to the consultation process as some CIM provider visits are more involved than conventional medical visits. Many patients with gastrointestinal conditions seek out CIM therapies, and prior work has demonstrated that the quality of the patient-provider interaction can improve health outcomes in irritable bowel syndrome, however, the impact of this interaction on gastroesophageal reflux disease (GERD) is unknown. We aimed to assess the safety and feasibility of conducting a 2x2 factorial design study preliminarily exploring the impact of the patient-provider interaction, and the effect of an over-the-counter homeopathic product, Acidil, on symptoms and health-related quality of life in subjects with GERD. Methods 24 subjects with GERD-related symptoms were randomized in a 2x2 factorial design to receive 1) either a standard visit based on an empathic conventional primary care evaluation or an expanded visit with questions modeled after a CIM consultation and 2) either Acidil or placebo for two weeks. Subjects completed a daily GERD symptom diary and additional measures of symptom severity and health-related quality of life. Results There was no significant difference in GERD symptom severity between the Acidil and placebo groups from baseline to follow-up (p = 0.41), however, subjects who received the expanded visit were significantly more likely to report a 50% or greater improvement in symptom severity compared to subjects who received the standard visit (p = 0.01). Total consultation length, perceived empathy, and baseline beliefs in CIM were not associated with treatment outcomes. Conclusion An expanded patient-provider visit resulted in greater GERD symptom improvement than a standard empathic medical visit. CIM consultations may have enhanced placebo effects, and further studies to assess the

  10. Two randomized, double-blind, placebo-controlled studies of fluticasone propionate lotion 0.05% for the treatment of atopic dermatitis in subjects from 3 months of age.

    PubMed

    Eichenfield, Lawrence F; Miller, B H

    2006-04-01

    A novel lotion formulation of fluticasone propionate 0.05% has recently become available. Two large, randomized, placebo-controlled, double-blind studies involving 438 subjects demonstrated its efficacy and safety when applied once daily in the treatment of atopic dermatitis in subjects from 3 months to 87 years of age. The studies were limited to 4 weeks duration of use of fluticasone lotion and did not assess longer term efficacy or side effects.

  11. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients

    PubMed Central

    Fava, M; Johe, K; Ereshefsky, L; Gertsik, L G; English, B A; Bilello, J A; Thurmond, L M; Johnstone, J; Dickerson, B C; Makris, N; Hoeppner, B B; Flynn, M; Mischoulon, D; Kinrys, G; Freeman, M P

    2016-01-01

    We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4–20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions—Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort. PMID:26643541

  12. Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial

    PubMed Central

    2014-01-01

    Background HS219 (40 mg chitosan-loaded chewing gum) is designed to bind salivary phosphorus as an add-on to available phosphorus binders. We performed a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis (HD) patients with hyperphosphatemia as an add-on to phosphorus binders. Methods Sixty-eight HD patients who were maintained on calcium carbonate (n = 33) or sevelamer hydrochloride (n = 35) were enrolled. The primary end point was a change in serum phosphorus levels. Secondary end points included changes in levels of salivary phosphorus, serum calcium, parathyroid hormone (PTH), and intact fibroblast growth factor (iFGF) 23. Results Sixty-three patients chewed either HS219 (n = 35) or placebo (n = 28) for 30 min, three times a day, for 3 weeks. HS219 was well tolerated and safe. However, HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period. There were no significant effects of HS219 on reduction of salivary phosphorus, serum calcium, iPTH, or iFGF23 levels. Conclusions The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia. Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels. Trail registration ClinicalTrials.gov NCT01039428, 24 December, 2009. PMID:24968790

  13. Short-term therapeutic effects of 890-nanometer light therapy for chronic low back pain: a double-blind randomized placebo-controlled study.

    PubMed

    Hsieh, Ru-Lan; Lee, Wen-Chung

    2014-03-01

    We conducted a double-blind randomized placebo-controlled study to investigate the effects of short-term 890-nm light therapy in patients with chronic low back pain in a rehabilitation clinic. Thirty-eight women and 22 men with chronic low back pain (mean age, 60.3 years; range, 32-80 years) received 40-min sessions of hot-pack therapy combined with active or placebo 890-nm light therapy (wavelength = 890 nm, radiant power output = 6.24 W, power density = 34.7 mW/cm(2) for 40 min, total energy = 83.2 J/cm(2)) over the lower back three times weekly for 2 weeks. Participants were assessed before and after treatment by using a range of motion measurements, a visual analog scale evaluation of pain, the Multidimensional Fatigue Inventory, the Biodex Stability System, the Fear-Avoidance Beliefs Questionnaire, repeated chair-rising times, the Frenchay Activity Index, the Oswestry Disability Questionnaire (ODQ), and the Osteoarthritis Quality of Life Questionnaire. The severity of disability based on the ODQ score was used as the primary clinical outcome measurement. Compared to the baseline measurements, participants in the treatment group reported significant reductions in fear-avoidance beliefs regarding physical activity (P = 0.040) and work (P = 0.007) and in the severity of disability (P = 0.021). Treatment with hot-pack therapy and 890-nm light therapy was associated with reductions in the severity of disability and fear avoidance beliefs in patients with chronic low back pain.

  14. Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double-blinded, multicenter intervention trial.

    PubMed

    Malay, D Scot; Pressman, Martin M; Assili, Amir; Kline, Jason T; York, Shane; Buren, Ben; Heyman, Eugene R; Borowsky, Pam; LeMay, Carley

    2006-01-01

    Extracorporeal shockwave therapy (ESWT) has demonstrated efficacy in the treatment of recalcitrant proximal plantar fasciitis. The objective of this investigation was to compare the outcomes of participants treated with a new ESWT device with those treated with placebo. A total of 172 volunteer participants were randomized in a 2:1 active-to-placebo ratio in this prospective, double-blind, multicenter trial conducted between October 2003 and December 2004. ESWT (n=115) or placebo control (n=57) was administered on a single occasion without local or systemic anesthesia or sedation, after which follow-up was undertaken. The primary outcomes were the blind assessor's objective, and the participant's subjective assessments of heel pain during the first 3 months of follow-up. Participants were also followed up to 1 year to identify any adverse outcomes that may have been related to the shockwave device. On the visual analog scale, the blind assessor's objective assessment of heel pain displayed a mean reduction of 2.51 in the shockwave group and 1.57 in the placebo group; this difference was statistically significant (P=.045). On the visual analog scale, the participant's self-assessment of heel pain displayed a mean reduction of 3.39 in the shockwave group and 1.78 in the placebo group; this difference was statistically significant (P<.001). No serious adverse events were observed at any time. It was concluded that ESWT was both efficacious and safe for participants with chronic proximal plantar fasciitis that had been unresponsive to exhaustive conservative treatment.

  15. Improvement of Triglyceride Levels through the Intake of Enriched-β-Conglycinin Soybean (Nanahomare) Revealed in a Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Nishimura, Mie; Ohkawara, Tatsuya; Sato, Yuji; Satoh, Hiroki; Takahashi, Yoko; Hajika, Makita; Nishihira, Jun

    2016-01-01

    Soybean is recognized as a beneficial food with various functional components, such as β-conglycinin, which improves lipid metabolism. We evaluated the effects of the β-conglycinin-rich soybean Nanahomare on triglyceride (TG) levels. In this randomized, double-blind, placebo-controlled study, we divided 134 adult subjects into test and placebo groups that consumed processed food containing enriched-β-conglycinin soybean or low-β-conglycinin soybean. Hematological tests and body composition measurements were performed at weeks 0 (baseline), 4, 8, and 12 of the study period. TG levels significantly decreased in the test group compared with the placebo group at weeks 4 (change from baseline to week 4, placebo: 0.27 ± 44.13 mg/dL, test: −20.31 ± 43.74 mg/dL, p = 0.035) and 12 (change from baseline to week 12, placebo: −0.14 ± 65.83 mg/dL, test: −21.30 ± 46.21 mg/dL, p = 0.041). In addition, among subjects whose baseline TG levels were ≥100 mg/dL, the levels significantly improved in the test group at weeks 4 (p = 0.010) and 12 (p = 0.030), whereas the levels were not different between the test and placebo groups among those whose baseline levels were <100 mg/dL. These results suggest that the ingestion of enriched-β-conglycinin soybean improves serum TG levels. PMID:27529274

  16. Randomized, Double-blind, Placebo Controlled Trial of Polyphenon E in Prostate Cancer Patients before Prostatectomy: Evaluation of Potential Chemopreventive Activities

    PubMed Central

    Nguyen, Mike M; Ahmann, Frederick R; Nagle, Raymond B; Hsu, Chiu-Hsieh; Tangrea, Joseph A; Parnes, Howard L; Sokoloff, Mitchell H; Gretzer, Matthew B; Chow, H-H Sherry

    2011-01-01

    Compelling pre-clinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double-blind, placebo controlled trial of Polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3–6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on Polyphenon E but was not statistically significant. The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3–6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease. PMID:22044694

  17. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study of RG7667, an Anticytomegalovirus Combination Monoclonal Antibody Therapy, in Healthy Adults

    PubMed Central

    Ishida, Julie H.; Burgess, Tracy; Derby, Michael A.; Brown, Pearline A.; Maia, Mauricio; Deng, Rong; Emu, Brinda; Feierbach, Becket; Fouts, Ashley E.; Liao, X. Charlene

    2015-01-01

    Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody; n = 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses; n = 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses; n = 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.) PMID:26055360

  18. Reduction of pain thresholds in fibromyalgia after very low-intensity magnetic stimulation: A double-blinded, randomized placebo-controlled clinical trial

    PubMed Central

    Maestú, Ceferino; Blanco, Manuel; Nevado, Angel; Romero, Julia; Rodríguez-Rubio, Patricia; Galindo, Javier; Lorite, Juan Bautista; de las Morenas, Francisco; Fernández-Argüelles, Pedro

    2013-01-01

    BACKGROUND: Exposure to electromagnetic fields has been reported to have analgesic and antinociceptive effects in several organisms. OBJECTIVE: To test the effect of very low-intensity transcranial magnetic stimulation on symptoms associated with fibromyalgia syndrome. METHODS: A double-blinded, placebo-controlled clinical trial was performed in the Sagrado Corazón Hospital, Seville, Spain. Female fibromyalgia patients (22 to 50 years of age) were randomly assigned to either a stimulation group or a sham group. The stimulation group (n=28) was stimulated using 8 Hz pulsed magnetic fields of very low intensity, while the sham group (n=26) underwent the same protocol without stimulation. Pressure pain thresholds before and after stimulation were determined using an algometer during the eight consecutive weekly sessions of the trial. In addition, blood serotonin levels were measured and patients completed questionnaires to monitor symptom evolution. RESULTS: A repeated-measures ANOVA indicated statistically significant improvement in the stimulation group compared with the control group with respect to somatosensory pain thresholds, ability to perform daily activities, perceived chronic pain and sleep quality. While improvement in pain thresholds was apparent after the first stimulation session, improvement in the other three measures occurred after the sixth week. No significant between-group differences were observed in scores of depression, fatigue, severity of headaches or serotonin levels. No adverse side effects were reported in any of the patients. CONCLUSIONS: Very low-intensity magnetic stimulation may represent a safe and effective treatment for chronic pain and other symptoms associated with fibromyalgia. PMID:24308025

  19. Intake of black-vinegar-mash-garlic enhances salivary release of secretory IgA: A randomized, double-blind, placebo-controlled, parallel-group study

    PubMed Central

    NAKASONE, YASUSHI; SATO, NORIMASA; AZUMA, TAKAYUKI; HASUMI, KEIJI

    2016-01-01

    Several previous studies have provided evidence that suggests the beneficial effects of garlic and black vinegar on human health, including benefits to immune function. The preliminary study indicated that the intake of black-vinegar-mash-garlic-containing food, created from aged garlic pickled in the mash of black vinegar, enhanced the release of secretory immunoglobulin A (sIgA) in the saliva. The aim of the present study was to evaluate the effect of the food in a randomized, double-blind, placebo-controlled, parallel-group trial. The trial was conducted in subjects aged between 30 and 60 years whose rate of salivary sIgA release was moderately low. Subjects consumed 2.49 g of placebo or black-vinegar-mash-garlic-containing food (active food) daily for 8 weeks. The data obtained with 54 eligible subjects (n=28 and 26 for placebo and active, respectively) were analyzed for efficacy. The rates of salivary sIgA release in the active food group (35.9±84.6 and 47.9±123.4 µg/min at weeks 4 and 8 of intake; changes from pretrial value) were higher compared to the respective rates in the placebo food group (−12.3±72.1 and −3.2±85.9 µg/min, P=0.028 and 0.082, respectively). These findings indicate that intake of black-vinegar-mash-garlic-containing food enhanced the intraoral immune response. There was no adverse event associated with the intake of active food. PMID:27347407

  20. Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial.

    PubMed

    Burton, Jeremy P; Drummond, Bernadette K; Chilcott, Chris N; Tagg, John R; Thomson, W Murray; Hale, John D F; Wescombe, Philip A

    2013-06-01

    The prevalence of dental caries continues to increase, and novel strategies to reverse this trend appear necessary. The probiotic Streptococcus salivarius strain M18 offers the potential to confer oral health benefits as it produces bacteriocins targeting the important cariogenic species Streptococcus mutans, as well as the enzymes dextranase and urease, which could help reduce dental plaque accumulation and acidification, respectively. In a randomized double-blind, placebo-controlled study of 100 dental caries-active children, treatment with M18 was administered for 3 months and the participants were assessed for changes to their plaque score and gingival and soft-tissue health and to their salivary levels of S. salivarius, S. mutans, lactobacilli, β-haemolytic streptococci and Candida species. At treatment end, the plaque scores were significantly (P = 0.05) lower for children in the M18-treated group, especially in subjects having high initial plaque scores. The absence of any significant adverse events supported the safety of the probiotic treatment. Cell-culture analyses of sequential saliva samples showed no differences between the probiotic and placebo groups in counts of the specifically enumerated oral micro-organisms, with the exception of the subgroup of the M18-treated children who appeared to have been colonized most effectively with M18. This subgroup exhibited reduced S. mutans counts, indicating that the anti-caries activity of M18 probiotic treatments may be enhanced if the efficiency of colonization is increased. It was concluded that S. salivarius M18 can provide oral health benefits when taken regularly.

  1. Safety and Tolerability of an Antiasthma Herbal Formula (ASHMI™) in Adult Subjects with Asthma: A Randomized, Double-Blinded, Placebo-Controlled, Dose-Escalation Phase I Study

    PubMed Central

    Kelly-Pieper, Kristin; Patil, Sangita P.; Busse, Paula; Yang, Nan; Sampson, Hugh; Li, Xiu-Min; Kattan, Meyer

    2009-01-01

    Abstract Background Complementary and alternative medicines are increasingly used for the treatment of asthma in Western countries. A novel three-herb antiasthma herbal medicine intervention (ASHMI™; Sino-Lion Pharmaceutical Company; Shan Dong China) was demonstrated to be effective and safe in a murine model of asthma and in a preliminary clinical study in China. Objective The objective of this study was to evaluate the safety and tolerability of ASHMI in adult subjects with allergic asthma. Design Randomized, double-blind, placebo-controlled, dose escalation, phase I trial aimed at developing a botanical drug under the United States Food and Drug Administration Investigational New Drug title. Interventions Subjects received one of three doses of ASHMI or placebo: 600 mg (2 capsules); 1200 mg (4 capsules); or 1800 mg (6 capsules) twice daily for 1 week. Four (4) ASHMI and 2 placebo subjects were treated at each dose level. Subjects continued to use their conventional asthma medications for the duration of the study. Outcome measures Vital signs, physical examination, laboratory data, and electrocardiogram data were monitored throughout the study to assess occurrence of adverse events (AEs). Immunomodulatory studies were performed to evaluate the effect of ASHMI on cytokine, chemokine, and growth factor levels. Results Twenty (20) nonsmoking, allergic subjects with asthma were included in the study. Eight (8) subjects (4 ASHMI and 4 placebo) reported mild gastrointestinal symptoms. No grade 3 AEs were observed during the study period. Vital signs, electrocardiogram findings, and laboratory results obtained at pre- and post-treatment visits remained within normal range. No abnormal immunologic alterations were detected. Conclusion In this phase I study, ASHMI appeared to be safe and well tolerated by subjects with asthma. These findings allowed initiation of a larger phase II study to assess the efficacy of ASHMI. PMID:19586409

  2. A CONSORT-compliant, randomized, double-blind, placebo-controlled pilot trial of purified anthocyanin in patients with nonalcoholic fatty liver disease.

    PubMed

    Zhang, Pei-Wen; Chen, Feng-Xia; Li, Di; Ling, Wen-Hua; Guo, Hong-Hui

    2015-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid family, has been shown to ameliorate NAFLD-associated pathologies in rodents.The aim of this CONSORT-compliant pilot study is to evaluate the effects of anthocyanin supplementation on insulin resistance and liver injury biomarkers in patients with NAFLD.A total of 74 subjects with NAFLD were divided into 2 groups in this double-blind, randomized study. Patients received either purified anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12 weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and a set of biomarkers related to NAFLD were evaluated before and after intervention.No significant differences were observed in nutrient intake, physical activity, anthropometric parameters, or plasma lipid profile between patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin group exhibited significant decreases (P < 0.05, all comparisons) in plasma alanine aminotransferase (-19.1% vs 3.1%), cytokeratin-18 M30 fragment (-8.8% vs 5.6%) and myeloperoxidase (-75.0% vs -44.8%). Significant decreases from baseline in fasting blood glucose and homeostasis model assessment for insulin resistance were observed in the anthocyanin group; however, these differences were not significant relative to placebo controls. In addition, the oral glucose tolerance test indicated that anthocyanin supplementation significantly decreased the 2-hour loading glucose level compared to control (-18.7% vs -3.8%, P = 0.02).A 12-week supplement of purified anthocyanin improved insulin resistance, indicators of liver injury, and clinical evolution in NAFLD patients. Further studies are warranted to determine the clinical applications of anthocyanin in NAFLD.This trial was registered at clinicaltrials.gov as NCT01940263. PMID:25997043

  3. A Randomized, Placebo-Controlled, Active-Reference, Double-Blind, Flexible-Dose Study of the Efficacy of Vortioxetine on Cognitive Function in Major Depressive Disorder

    PubMed Central

    Mahableshwarkar, Atul R; Zajecka, John; Jacobson, William; Chen, Yinzhong; Keefe, Richard SE

    2015-01-01

    This multicenter, randomized, double-blind, placebo-controlled, active-referenced (duloxetine 60 mg), parallel-group study evaluated the short-term efficacy and safety of vortioxetine (10–20 mg) on cognitive function in adults (aged 18–65 years) diagnosed with major depressive disorder (MDD) who self-reported cognitive dysfunction. Efficacy was evaluated using ANCOVA for the change from baseline to week 8 in the digit symbol substitution test (DSST)–number of correct symbols as the prespecified primary end point. The patient-reported perceived deficits questionnaire (PDQ) and physician-assessed clinical global impression (CGI) were analyzed in a prespecified hierarchical testing sequence as key secondary end points. Additional predefined end points included the objective performance-based University of San Diego performance-based skills assessment (UPSA) (ANCOVA) to measure functionality, MADRS (MMRM) to assess efficacy in depression, and a prespecified multiple regression analysis (path analysis) to calculate direct vs indirect effects of vortioxetine on cognitive function. Safety and tolerability were assessed at all visits. Vortioxetine was statistically superior to placebo on the DSST (P<0.05), PDQ (P<0.01), CGI-I (P<0.001), MADRS (P<0.05), and UPSA (P<0.001). Path analysis indicated that vortioxetine's cognitive benefit was primarily a direct treatment effect rather than due to alleviation of depressive symptoms. Duloxetine was not significantly different from placebo on the DSST or UPSA, but was superior to placebo on the PDQ, CGI-I, and MADRS. Common adverse events (incidence ⩾5%) for vortioxetine were nausea, headache, and diarrhea. In this study of MDD adults who self-reported cognitive dysfunction, vortioxetine significantly improved cognitive function, depression, and functionality and was generally well tolerated. PMID:25687662

  4. Adjunctive use of combination of super-pulsed laser and light-emitting diodes phototherapy on nonspecific knee pain: double-blinded randomized placebo-controlled trial.

    PubMed

    Leal-Junior, Ernesto Cesar Pinto; Johnson, Douglas Scott; Saltmarche, Anita; Demchak, Timothy

    2014-11-01

    Phototherapy with low-level laser therapy (LLLT) and light-emitting diode therapy (LEDT) has arisen as an interesting alternative to drugs in treatments of musculoskeletal disorders. However, there is a lack of studies investigating the effects of combined use of different wavelengths from different light sources like lasers and light-emitting diodes (LEDs) in skeletal muscle disorders. With this perspective in mind, this study aimed to investigate the effects of phototherapy with combination of different light sources on nonspecific knee pain. It was performed a randomized, placebo-controlled, double-blinded clinical trial. Eighty-six patients rated 30 or greater on the pain visual analogue scale (VAS) were recruited and included in study. Patients of LLLT group received 12 treatments with active phototherapy (with 905 nm super-pulsed laser and 875 and 640 nm LEDs, Manufactured by Multi Radiance Medical, Solon, OH, USA) and conventional treatment (physical therapy or chiropractic care), and patients of placebo group were treated at same way but with placebo phototherapy device. Pain assessments (VAS) were performed at baseline, 4th, 7th, and 10th treatments, after the completion of treatments and at 1-month follow-up visit. Quality of life assessments (SF-36®) were performed at baseline, after the completion of treatments and at 1-month follow-up visit. Our results demonstrate that phototherapy significantly decreased pain (p < 0.05) from 10th treatment to follow-up assessments and significantly improved (p < 0.05) SF-36® physical component summary at posttreatments and follow-up assessments compared to placebo. We conclude that combination of super-pulsed laser, red and infrared LEDs is effective to decrease pain and improve quality of life in patients with knee pain.

  5. Effects of low-level laser therapy on performance, inflammatory markers, and muscle damage in young water polo athletes: a double-blind, randomized, placebo-controlled study.

    PubMed

    Zagatto, Alessandro Moura; de Paula Ramos, Solange; Nakamura, Fábio Yuzo; de Lira, Fábio Santos; Lopes-Martins, Rodrigo Álvaro Brandão; de Paiva Carvalho, Rodrigo Leal

    2016-04-01

    This study aimed to evaluate the effects of 5 days of 810-nm low-level laser therapy (LLLT) intervention on inflammatory and muscle damage markers and performance in young water polo players. Twenty young male water polo players participated in the study, which was designed as a randomized, double-blinded, placebo-controlled trial. Active LLLT or an identical placebo LLLT were delivered to eight points on the adductor muscle region immediately after each training day. Performance was measured by a 200-m maximal swimming (P200) and a 30-s crossbar jump test (30CJ) which was performed every day before training, and blood samples were drawn pre and post the final LLLT intervention to measure interleukins (IL) and muscle damage markers. There was no significant change in the P200 exercise in the LLLT group compared with the placebo group but there was a moderate improvement in the 30CJ (8.7 ± 2.6 %). IL-1β and tumor necrosis factor-alpha presented increased (P < 0.016) concentration within group 48 h after the last LLLT intervention compared to pre, 0, and 24 h, but did not differ between groups. IL-10 increased over time in the placebo group and reached a moderate effect compared to the LLLT group. The creatine kinase decreased significantly (P = 0.049) over the time within the LLLT treatment group, but there was no significant change in lactate dehydrogenase (P = 0.150). In conclusion, LLLT resulted in a non-significant, but small to moderate effect on inflammatory and muscle damage markers and a moderate effect on performance in water polo players. In addition, the lack of positive results could be due to the small area covered by irradiation and this should be considered in future studies. PMID:26873498

  6. Enhanced Central Pain Processing of Fibromyalgia Patients is Maintained by Muscle Afferent Input: A Randomized, Double-Blind, Placebo Controlled Study

    PubMed Central

    Staud, Roland; Nagel, Susann; Robinson, Michael E.; Price, Donald D.

    2009-01-01

    Fibromyalgia syndrome (FM) is characterized by pain and widespread hyperalgesia to mechanical, thermal, and electrical stimuli. Despite convincing evidence for central sensitization of nociceptive pain pathways, the role of peripheral tissue impulse input in the initiation and maintenance of FM is unclear. Therefore this randomized, double-blind, placebo-controlled trial of 22 normal female controls (NC) and 28 female FM subjects tested the effects of trapezius muscle (TrapM) tender point injections with 1% lidocaine on local pain thresholds as well as on remote heat hyperalgesia at the forearm. Prior to muscle injections shoulder pain was standardized by tonic mechanical muscle stimulation, resulting in local pain ratings of 4.0 ± 0.5 VAS units. Tonic muscle stimulation was interrupted for the TrapM injections but continued afterwards at the same level. NC as well as FM subjects experienced significant increases of TrapM pressure pain-thresholds from lidocaine but not placebo injections (p <.001). Additionally, heat-hyperalgesia of FM participants was significantly reduced at areas remote from the injection site (forearm) by lidocaine but not placebo (p = .02). Neither lidocaine nor saline injections significantly affected clinical FM pain ratings, a result most likely due to the very low dose of lidocaine (50 mg) used in this trial. Conclusion: Lidocaine injections increased local pain-thresholds and decreased remote secondary heat hyperalgesia in FM patients, emphasizing the important role of peripheral impulse input in maintaining central sensitization in this chronic pain syndrome; similar to other persistent pain conditions like irritable bowel syndrome and complex regional pain syndrome. PMID:19540671

  7. Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: a Double-Blinded, Randomized Placebo Controlled Pilot Study in Critically Ill Neonates

    PubMed Central

    Calkins, Kara L.; Sanchez, Lauren A.; Tseng, Chi-Hong; Faull, Kym F.; Yoon, Alexander J.; Ryan, Christopher M.; Le, Thuc; Shew, Stephen B.

    2015-01-01

    Background This study’s objective was to determine if parenteral cysteine when compared to isonitrogenous non-cysteine supplementation increases erythrocyte reduced glutathione (GSH) in neonates at high risk for inflammatory injury. Material and Methods Neonates with a score for neonatal acute physiology (SNAP) > 10 requiring mechanical ventilation and parenteral nutrition (PN) were randomized in a double-blinded, placebo controlled study to receive parenteral cysteine-HCl (CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/day for ≥ seven days. A six-hour [13C2] glycine IV infusion was administered at study week one to determine fractional synthetic rate of glutathione (FSR-GSH). Results Baseline characteristics were similar between the CYS (n=17) and ISO groups (n=21). Erythrocyte GSH and total glutathione concentrations, GSH:oxidized glutathione (GSSG), and FSR-GSH after treatment were not different between groups. However, the CYS group had a larger individual positive change in GSH and total glutathione (infusion day – baseline) compared to the ISO group (p=0.02 for each). After adjusting for treatment, a lower enrollment weight and red blood cell (RBC) transfusion were associated with a decreased change in total glutathione and GSH (p< 0.05 for each). Conclusion When compared to isonitrogenous non-cysteine supplementation, high dose cysteine supplementation for at least one week in critically ill neonates resulted in a larger and more positive individual change in glutathione. Smaller infants and those who received transfused blood demonstrated less effective change in glutathione with cysteine supplementation. The benefit of cysteine remains promising and deserves further investigation. PMID:25139979

  8. A pilot placebo-controlled, double-blind, and randomized study on the cognition-enhancing benefits of a proprietary chicken meat ingredient in healthy subjects

    PubMed Central

    2013-01-01

    Background It has long been postulated that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that could be responsible for the action of diet on brain health and cognitive function. Here, through a double-blind, randomized, placebo-controlled trial, we asked if the newly discovered chicken meat ingredient-168 (CMI-168) could be beneficial to the cognitive function in healthy adults. Methods Normal, healthy subjects were supplemented with either placebo or CMI-168 for 6 weeks. The subjects were given a series of cognitive tests to examine their levels of cognitive functioning at the beginning and end of supplementation, as well as two weeks after termination of supplementation. The combination of these tests, namely Digit Span Backwards, Letter-Number Sequencing, and the Rey Auditory Verbal Learning Test (RAVLT), was used to assess the subjects’ attention and working memory. For all comparisons, the probability level of p < 0.05 was taken as statistically significant using repeated measure 2-way ANOVA followed by Bonferroni post-hoc test. Results Overall, subjects supplemented with CMI-168 showed significantly (p < 0.01) better performance in all cognitive tests after 6 weeks’ supplementation compared to control and such superior performance was maintained even 2 weeks after termination of supplementation. Conclusions The present study reveals the cognition-enhancing properties of a recently developed chicken meat ingredient, likely arising from the promotion of attention and prefrontal cortex functions. PMID:23945213

  9. Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial.

    PubMed

    Burton, Jeremy P; Drummond, Bernadette K; Chilcott, Chris N; Tagg, John R; Thomson, W Murray; Hale, John D F; Wescombe, Philip A

    2013-06-01

    The prevalence of dental caries continues to increase, and novel strategies to reverse this trend appear necessary. The probiotic Streptococcus salivarius strain M18 offers the potential to confer oral health benefits as it produces bacteriocins targeting the important cariogenic species Streptococcus mutans, as well as the enzymes dextranase and urease, which could help reduce dental plaque accumulation and acidification, respectively. In a randomized double-blind, placebo-controlled study of 100 dental caries-active children, treatment with M18 was administered for 3 months and the participants were assessed for changes to their plaque score and gingival and soft-tissue health and to their salivary levels of S. salivarius, S. mutans, lactobacilli, β-haemolytic streptococci and Candida species. At treatment end, the plaque scores were significantly (P = 0.05) lower for children in the M18-treated group, especially in subjects having high initial plaque scores. The absence of any significant adverse events supported the safety of the probiotic treatment. Cell-culture analyses of sequential saliva samples showed no differences between the probiotic and placebo groups in counts of the specifically enumerated oral micro-organisms, with the exception of the subgroup of the M18-treated children who appeared to have been colonized most effectively with M18. This subgroup exhibited reduced S. mutans counts, indicating that the anti-caries activity of M18 probiotic treatments may be enhanced if the efficiency of colonization is increased. It was concluded that S. salivarius M18 can provide oral health benefits when taken regularly. PMID:23449874

  10. A Systematic Review of Randomized, Double-Blind, Placebo-Controlled Trials Examining the Clinical Efficacy of Vitamin D in Multiple Sclerosis

    PubMed Central

    Pozuelo-Moyano, Beatriz; Benito-León, Julián; Mitchell, Alex J.; Hernández-Gallego, Jesús

    2013-01-01

    Background An association between multiple sclerosis (MS) prevalence as well as MS mortality and vitamin D nutrition has led to the hypothesis that high levels of vitamin D could be beneficial for MS. The purpose of this systematic review is to establish whether there is evidence for or against vitamin D in the treatment of MS. Methods Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the clinical effect of vitamin D on MS in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score. Results Five trials were located meeting the selection criteria. Of the five trials, four showed no effect of vitamin D on any outcome, and one showed a significant effect, namely upon reduction in the number of T1 enhancing lesions on brain magnetic resonance imaging. Three studies commented on adverse effects of vitamin D, with gastrointestinal adverse effects being the most frequently reported. The literature is limited by small study sizes (studies size ranged from 23 to 68 patients) and heterogeneity of dosing, form of vitamin D tested (vitamin D3 in four trials, and vitamin D2 in one), and outcome clinical measures. Therefore, a meta-analysis was not performed. Conclusions The evidence for vitamin D as a treatment for MS is inconclusive. Larger studies are warranted to assess the effect of vitamin D on clinical outcomes in patients with MS. We further encourage researchers to also test the effect of vitamin D on the health-related quality of life experienced by patients and their families. PMID:23257784

  11. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.

    PubMed Central

    Levitan, R D; Shen, J H; Jindal, R; Driver, H S; Kennedy, S H; Shapiro, C M

    2000-01-01

    OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings. PMID:11022398

  12. Effects of vitamin D supplementation on metabolic indices and hs-CRP levels in gestational diabetes mellitus patients: a randomized, double-blinded, placebo-controlled clinical trial

    PubMed Central

    Yazdchi, Roya; Asghari-Jafarabadi, Mohammad; Sahhaf, Farnaz

    2016-01-01

    BACKGROUND/OBJECTIVES Vitamin D plays an important role in the etiology of gestational diabetes mellitus (GDM). This study evaluated the effect of vitamin D supplementation on metabolic indices and hs-C-reactive protein (CRP) levels in GDM patients. SUBJECTS/METHODS The study was a randomized, placebo-controlled, double-blinded clinical trial. Seventy-six pregnant women with GDM and gestational age between 24-28 weeks were assigned to receive four oral treatments consisting of 50,000 IU of vitamin D3 (n = 38) or placebo (n = 38) once every 2 weeks for 2 months. Fasting blood glucose (FG), insulin, HbA1c, 25-hydroxyvitamin D, lipid profile, hs-CRP, and homeostasis model assessment-insulin resistance (HOMA-IR) were measured before and after treatment. Independent and paired t-tests were used to determine intra- and intergroup differences, respectively. ANCOVA was used to assess the effects of vitamin D supplementation on biochemical parameters. RESULTS Compared with the placebo group, in the vitamin D group, the serum level of 25-hydroxyvitamin D increased (19.15 vs. -0.40 ng/ml; P < 0.01) and that of FG (-4.72 vs. 5.27 mg/dl; P = 0.01) as well as HbA1c (-0.18% vs. 0.17%; P = 0.02) decreased. Improvements in the lipid profiles were observed in the vitamin D group, but without statistical significance. Significant increases in concentrations of hs-CRP, FG, HbA1c, total cholesterol, and LDL cholesterol were observed in the placebo group. No significant change in fasting insulin and HOMA-IR was observed in either group. CONCLUSIONS In GDM patients, vitamin D supplementation improved FG and HbA1c but had no significant effects on lipid profile or hs-CRP. PMID:27247730

  13. A proprietary blend of quail egg for the attenuation of nasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study

    PubMed Central

    Benichou, Annie-Claude; Armanet, Marion; Bussière, Anthony; Chevreau, Nathalie; Cardot, Jean-Michel; Tétard, Jan

    2014-01-01

    Occasional rhinitis symptoms caused by exposure to pollution or allergens is a growing concern. Based first on empirical observation of a lesser occurrence of allergies in quail farmers and then scientific works on ovomucoids properties, we developed a dietary supplement for the relief of such occasional rhinitis symptoms. The objective of the study was to determine whether one acute oral dose of the study product attenuates nasal provocation and other allergy-related symptoms after exposure to a standardized allergenic challenge as compared to placebo. Healthy subjects were recruited to participate in a randomized, double-blind, two-arm crossover, placebo-controlled, clinical trial. One acute dose of either the active study product (proprietary blend of quail egg) or placebo was given concomitantly to the standardized allergenic challenge. The primary endpoint was peak nasal inspiratory flow (PNIF) measurement and the secondary endpoints were subjects' perceived feelings of well-being based on Visual Analog Scale (VAS) scores for allergy-related symptoms, as well as immunoglobulin E count. Forty-three healthy subjects were enrolled and evaluable in a per protocol analysis. A gradual increase in PNIF from nadir up to Time 120 reflected the normal, gradual recovery from nasal obstruction induced by allergenic challenge for both the active and the placebo groups. At all postchallenge time points, the active group had higher PNIF values compared to the placebo group, indicating that the active product was associated with fewer symptoms and reduced intensity of these symptoms. The active product resulted also in statistically significant improvements of most of the subjects' perceived feelings of well-being based on VAS scores. No adverse events occurred during the study. In conclusion, the dietary supplement consisting of proprietary blend made of quail eggs provides fast and efficient relief of allergic rhinitis symptoms caused by the most common outdoor and indoor

  14. Short-term Curcuminoid Supplementation for Chronic Pulmonary Complications due to Sulfur Mustard Intoxication: Positive Results of a Randomized Double-blind Placebo-controlled Trial.

    PubMed

    Panahi, Y; Ghanei, M; Bashiri, S; Hajihashemi, A; Sahebkar, A

    2015-11-01

    Pulmonary problems are among the most frequent chronic complications of sulfur mustard (SM) intoxication and are often accompanied by deregulated production of pro-inflammatory cytokines. Curcuminoids, comprising curcumin, demethoxycurcumin and bisdemethoxycurcumin, are phytochemicals with remarkable anti-inflammatory properties that are derived from dried rhizomes of the plant Curcuma longa L. (turmeric). The present pilot study aimed to investigate the clinical effects of supplementation with curcuminoids on markers of pulmonary function and systemic inflammation in SM-intoxicated subjects. In a randomized double-blind placebo-controlled trial, 89 male subjects who were suffering from chronic SM-induced pulmonary complications were recruited and assigned to either curcuminoids (500 mg TID per oral; n=45) or placebo (n=44) for a period of 4 weeks. Efficacy measures were changes in the spirometric parameters (FVC, FEV1, FEV1/FVC) and serum levels of inflammatory mediators including interleukins 6 (IL-6) and 8 (IL-8), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). 78 subjects completed the trial. Although FEV1 and FVC remained comparable between the groups, there was a greater effect of curcuminoids vs. placebo in improving FEV1/FVC (p=0.002). Curcuminoids were also significantly more efficacious compared to placebo in modulating all assessed inflammatory mediators: IL-6 (p<0.001), IL-8 (p=0.035), TNFα (p<0.001), TGFβ (p<0.001), substance P (p=0.016), hs-CRP (p<0.001), CGRP (p<0.001) and MCP-1 (p<0.001). Curcuminoids were safe and well-tolerated throughout the trial. Short-term adjunctive therapy with curcuminoids can suppress systemic inflammation in patients suffering from SM-induced chronic pulmonary complications. PMID:25268878

  15. Safety of zinc gluconate glycine (Cold-Eeze) in a geriatric population: a randomized, placebo-controlled, double-blind trial.

    PubMed

    Silk, Raymond; LeFante, Carolyn

    2005-01-01

    Zinc gluconate glycine lozenges are an over-the-counter homeopathic remedy that significantly reduced the duration and severity of common colds in adults in 2 independent clinical trials. To evaluate the safety of zinc gluconate glycine lozenges in elderly individuals with 1 or more health conditions, with or without a cold. This randomized, double-blind, placebo-controlled, parallel-group trial enrolled men and women between 60 and 91 years of age, who self-administered 1 zinc gluconate glycine or placebo lozenge every 3 to 4 hours for 6 days. One or more of the following conditions was present in the study population: arthritis, cancer, depression, heart disease, hypertension, lung disease, osteoporosis, prostate disease, and stroke. Assessments were performed at baseline and at 7 (+/-1 day) and 14 days. The safety evaluation considered physical examinations, clinical laboratory tests, vital signs, adverse events, and concomitant medications. Of 75 persons enrolled, 66 completed the study. Safety assessments demonstrated no clinically significant differences between treatment groups. Four participants taking zinc tablets and 3 participants taking placebo tablets reported mild adverse events. Of those participants taking zinc tablets, 6 adverse events were possibly related to the study product and 2 adverse events were probably related to the study product. Of those participants taking placebo tablets, 3 adverse events were reported that were possibly related to the study product. No serious or clinically significant adverse events were noted. Zinc gluconate glycine lozenges are safe and well tolerated by a geriatric population and are suitable for prophylactic or therapeutic use to reduce the duration or severity of the common cold. PMID:16280656

  16. A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Tenecteplase for Improvement of Hemodialysis Catheter Function: TROPICS 3

    PubMed Central

    Goldman, Jesse; Spiegel, David M.; Roer, David; Ntoso, K. Adu; Blaney, Martha; Jacobs, Joan; Gillespie, Barbara S.; Begelman, Susan M.

    2010-01-01

    Background and objectives: Despite widespread use of tunneled hemodialysis (HD) catheters, their utility is limited by the development of thrombotic complications. To address this problem, this study investigated whether the thrombolytic agent tenecteplase can restore blood flow rates (BFRs) in dysfunctional HD catheters. Design, setting, participants, & measurements: In this randomized, double-blind study, patients with dysfunctional tunneled HD catheters, defined as a BFR <300 ml/min at −250 mmHg pressure in the arterial line, received 1-hour intracatheter dwell with tenecteplase (2 mg) or placebo. The primary endpoint was the percentage of patients with BFR ≥300 ml/min and an increase of ≥25 ml/min above baseline 30 minutes before and at the end of HD. Safety endpoints included the incidence of hemorrhagic, thrombotic, and infectious complications. Results: Eligible patients (n = 149) were treated with tenecteplase (n = 74) or placebo (n = 75). Mean baseline BFR was similar for the tenecteplase and placebo groups at 151 and 137 ml/min, respectively. After a 1-hour dwell, 22% of patients in the tenecteplase group had functional catheters compared with 5% among placebo controls (P = 0.004). At the end of dialysis, mean change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the placebo group (P = 0.008). Four catheter-related bloodstream infections (one tenecteplase, three placebo) and one thrombosis (tenecteplase) were observed. There were no reports of intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications. Conclusions: Tenecteplase improved HD catheter function and had a favorable safety profile compared with placebo. PMID:20133491

  17. The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    Kearns, MD; Binongo, JNG; Watson, D; Alvarez, JA; Lodin, D; Ziegler, TR; Tangpricha, V

    2014-01-01

    BACKGROUND/OBJECTIVES Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. SUBJECTS/METHODS In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. RESULTS At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5 ± 6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. CONCLUSIONS A dose of 250 000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency. PMID:25271011

  18. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

    PubMed Central

    Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W.; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H.; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

    2016-01-01

    Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. PMID:26903532

  19. Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study.

    PubMed

    Mathias, J R; Clench, M H; Abell, T L; Koch, K L; Lehman, G; Robinson, M; Rothstein, R; Snape, W J

    1998-06-01

    We have previously reported impressive results in using a gonadotropin-releasing hormone analog, leuprolide acetate (Lupron), in the treatment of moderate to severe symptoms (especially abdominal pain and nausea) in patients with functional bowel disease (FBD). Pain is the hallmark of patients with FBD, and there is no consistent therapy for the treatment of these patients. The purpose of the present study was to expand the investigation to study similar patients (menstruating females) in a multicenter, double-blind, placebo-controlled, randomized study using Lupron Depot (which delivers a continuous dose of drug for one month), 3.75 mg (N = 32) or 7.5 mg (N = 33), or placebo (N = 35) given intramuscularly every four weeks for 16 weeks. Symptoms were assessed using daily diary cards to record abdominal pain, nausea, vomiting, early satiety, anorexia, bloating, and altered bowel habits. Additional assessment tools were quality of life questionnaires, psychological profile, oral-to-cecal transit using the hydrogen breath test, antroduodenal manometry, reproductive hormone levels, and global evaluations by both patient and investigator. Patients in both Lupron Depot-treated groups showed consistent improvement in symptoms; however, only the Lupron Depot 7.5 mg group showed a significant improvement for abdominal pain and nausea compared to placebo (P < 0.001). Patient quality of life assessments and global evaluations completed by both patient and investigators were highly significant compared to placebo (P < 0.001). All reproductive hormone levels significantly decreased for both Lupron Depot-treated groups by week 4 and were significantly different compared to placebo at week 16 (P < 0.001). This study shows that leuprolide acetate is effective in controlling the debilitating symptoms of abdominal pain and nausea in patients with FBD.

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

    PubMed Central

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

    2015-01-01

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

  1. Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

    PubMed Central

    2013-01-01

    Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a

  2. A Randomized, Double-Blind, Placebo-Controlled Study of Modafinil Film-Coated Tablets in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Greenhill, Laurence L.; Biederman, Joseph; Boellner, Samuel W.; Rugino, Thomas A.; Sangal, R. Bart; Earl, Craig Q.; Jiang, John G.; Swanson, James M.

    2006-01-01

    Objective: To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD). Method: In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV…

  3. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial

    PubMed Central

    2013-01-01

    Background Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population. Methods This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight. Results A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of

  4. Efficacy and Safety of Tangshen Formula on Patients with Type 2 Diabetic Kidney Disease: A Multicenter Double-Blinded Randomized Placebo-Controlled Trial

    PubMed Central

    Li, Ping; Chen, Yiping; Liu, Jianping; Hong, Jing; Deng, Yueyi; Yang, Fang; Jin, Xiuping; Gao, Jing; Li, Jing; Fang, Hui; Liu, Geling; Shi, Liping; Du, Jinhang; Li, Yang; Yan, Meihua; Wen, Yumin; Yang, Wenying

    2015-01-01

    Background Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD. Methods The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events. Findings After 24 weeks of treatment, no statistically significant difference in UAER (TSF −19.53 μg/min compared with placebo −7.01 μg/min, with a mean difference of −12.52 μg/min; 95%CI, −68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF−0.21 g compared with placebo 0.36 g, with a mean difference of −0.57g; 95%CI, −1.05 to −0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, −0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events. Conclusions Based on conventional

  5. The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial

    PubMed Central

    Hua, Wei; Gao, Run-Lin; Zhao, Bu-Chang; Wang, Jing; Chen, Xu-Hua; Cai, Chi; Zhang, Shu

    2015-01-01

    Background: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. Methods: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. Results: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%, P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%, P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. Conclusions: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC

  6. Creatine Fails to Augment the Benefits from Resistance Training in Patients with HIV Infection: A Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Sakkas, Giorgos K.; Mulligan, Kathleen; DaSilva, Makani; Doyle, Julie W.; Khatami, Hootan; Schleich, Thomas; Kent-Braun, Jane A.; Schambelan, Morris

    2009-01-01

    Background Progressive resistance exercise training (PRT) improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients. Methodology/Principal Findings This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV–positive men (20 creatine, 20 placebo) enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance). The main outcome measurements included muscle strength (one repetition maximum), energetics (31P magnetic resonance spectroscopy), composition and size (magnetic resonance imaging), as well as total body composition (dual-energy X-ray absorptiometry). Thirty-three subjects completed the study (17 creatine, 16 placebo). Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI −9.5% to 13.9%) in creatine and placebo, respectively). There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM) increased to a significantly greater extent with creatine. Conclusions

  7. Effect of Linum usitatissimum L. (linseed) oil on mild and moderate carpal tunnel syndrome: a randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Carpal tunnel syndrome is known as the most common entrapment neuropathy. Conservative treatments cannot reduce the symptomatic severity satisfactorily; therefore, effectiveness of Linum usitatissimum L. (linseed) oil on carpal tunnel syndrome, as a complementary treatment, was evaluated in the current study. Linseed oil is a well-known preparation in Iranian traditional medicine and its analgesic, anti-inflammatory and anti-oxidative effects have been shown in previous studies. Methods A randomized, double-blind, placebo-controlled clinical trial was conducted. One hundred patients (155 hands) with idiopathic mild to moderate carpal tunnel syndrome aged between 18 and 65 years old were randomized in two parallel groups. These two groups were treated during 4 weeks with topical placebo and linseed oil. In addition, a night wrist splint was prescribed for both groups. Symptomatic severity and functional status were measured using Boston Carpal Tunnel Questionnaire. In addition, median sensory nerve conduction velocity, motor distal latency, sensory distal latency and compound latency as electrodiagnostic parameters were measured at baseline and after the intervention period. Results After the intervention, significant improvement was observed regarding Boston Carpal Tunnel Questionnaire symptomatic severity and functional status mean differences (p <0.001) in the linseed oil group compared with those in the placebo group. Also, regarding the mean differences of both groups, significant improvement of nerve conduction velocity of the median nerve was seen in the linseed oil group by a value of 2.38 m/sec (p < 0.05). However, motor distal latency and sensory distal latency of the median nerve showed no between-group significant changes (p = 0.14 for both items). Finally, compound latency was improved slightly in the case group, comparing mean differences between the groups (p <0.05). No significant adverse events were reported from using linseed

  8. Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Gregory, William L.; Leo, Michael; Kraemer, Dale; Bone, Kerry; Oken, Barry

    2008-01-01

    Abstract Objectives Study aims were to evaluate effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and its safety and tolerability in healthy elderly study participants. Design The study was a randomized, double-blind, placebo-controlled clinical trial with a placebo run-in of 6 weeks and a treatment period of 12 weeks. Setting/location Volunteers were recruited from the community to a clinic in Portland, Oregon by public notification. Subjects Fifty-four (54) participants, 65 or older (mean 73.5 years), without clinical signs of dementia, were recruited and randomized to Bacopa or placebo. Forty-eight (48) completed the study with 24 in each group. Interventions Standardized B. monnieri extract 300 mg/day or a similar placebo tablet orally for 12 weeks. Outcome measures The primary outcome variable was the delayed recall score from the Rey Auditory Verbal Learning Test (AVLT). Other cognitive measures were the Stroop Task assessing the ability to ignore irrelevant information, the Divided Attention Task (DAT), and the Wechsler Adult Intelligence Scale (WAIS) letter-digit test of immediate working memory. Affective measures were the State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression scale (CESD)-10 depression scale, and the Profile of Mood States. Vital signs were also monitored. Results Controlling for baseline cognitive deficit using the Blessed Orientation–Memory–Concentration test, Bacopa participants had enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant, with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse events (Bacopa n = 9

  9. A Randomized, Double Blind, Placebo-Controlled, Multicenter Phase II Trial of Allisartan Isoproxil in Essential Hypertensive Population at Low-Medium Risk

    PubMed Central

    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

    Background 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. Methods and Findings 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 (P<0.01). The rate of effective blood pressure control in Allisartan Isoproxil group was significantly higher than in placebo group at week 4 (61.3% vs 50.0%, P<0.05) and week 8 (67.2% vs 48.6%, P<0.01). In terms of safety 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. Conclusions/Significance Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk. Trial Registration http

  10. Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study

    PubMed Central

    Kanzaki, Noriyuki; Ono, Yoshiko; Shibata, Hiroshi; Moritani, Toshio

    2015-01-01

    Background The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. Methods A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. Results In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren–Lawrence (K–L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, P<0.05) was significantly greater in the GCQID group than in the placebo group in subjects with K–L grade I. No adverse effect of treatment was identified in the safety assessment. Conclusion In subjects with knee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions. PMID:26604721

  11. Parenteral troxerutin and carbazochrome combination in the treatment of post-hemorrhoidectomy status: a randomized, double-blind, placebo-controlled, phase IV study.

    PubMed

    Basile, M; Gidaro, S; Pacella, M; Biffignandi, P M; Gidaro, G S

    2001-01-01

    Flavonoids, such as troxerutin, have been shown to be safe and effective agents for the treatment of chronic venous insufficiency. The fixed combination between troxerutin 150 mg and carbazochrome 1.5 mg (Fleboside ampoules) was previously shown to have a good efficacy and safety profile in non-surgical patients with acute uncomplicated hemorrhoids. The purpose of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and tolerability of the active combination in the treatment of post-hemorrhoidectomy patients. 30 patients were randomized to receive one of two treatments: troxerutin 150 mg and carbazochrome 1.5 mg, or placebo, i.m. 3 ml ampoules twice a day for five consecutive days after the surgical procedure, starting from the day of surgery. Efficacy parameters were assessed as follows: at baseline (T1), after the first administration (T2; day of surgery), the second day after the surgical procedure (T3), and the fifth day after the surgical procedure (T4); hemorrhoidal symptoms based on a visual analogue scale (VAS): pain, discharge, bleeding, inflammation, and pruritus; analgesic intake, if any; time to restore a physiological defecation; edema evaluation (based on a four-point scale: 0 = absent; 1 = mild; 2 = moderate; 3 = severe); camera pictures taken at T1 and T4 (in selected patients); and blood coagulation tests. Analysis between treatment groups revealed a highly significant difference at T3 and T4 for the total VAS score (p = 0.007 and p = 0.001, respectively) in favor of the active combination treatment. A statistically significant difference was also observed for bleeding and pruritus at T3 and for these two parameters and both inflammation and edema at T4 (p < 0.001) in favor of the active combination group. No adverse events were reported. Neither the active combination nor placebo affected blood coagulation tests. We conclude that intramuscular administration of the fixed combination of troxerutin 150 mg and

  12. [The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study].

    PubMed

    Konrad, F; Schoenberg, M H; Wiedmann, H; Kilian, J; Georgieff, M

    1995-09-01

    Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury, sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAC) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. METHODS. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. RESULTS. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in

  13. Tramiprosate in mild-to-moderate Alzheimer’s disease – a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study)

    PubMed Central

    Aisen, Paul S.; Gauthier, Serge; Ferris, Steven H.; Saumier, Daniel; Haine, Denis; Garceau, Denis; Duong, Anh; Suhy, Joyce; Oh, Joonmi; Lau, Wan C.; Sampalis, John

    2011-01-01

    Introduction The aim of the study was to assess the clinical efficacy, safety, and disease-modification effects of tramiprosate (homotaurine, ALZHEMEDTM) in mild-to-moderate Alzheimer’s disease (AD). Material and methods Double-blind, placebo-controlled, randomized trial in 67 clinical centres across North America. Patients aged ≥ 50 years, with mild-to-moderate AD (Mini-Mental State Examination score between 16 and 26) and on stable doses of cholinesterase inhibitors, alone or with memantine. Intervention: 78-week treatment with placebo, tramiprosate 100 mg or tramiprosate 150 mg BID. Measurements: Alzheimer Disease Assessment Scale – cognitive subscale (ADAS-cog) and Clinical Dementia Rating – Sum of Boxes (CDR-SB) assessments were performed at baseline and every 13 weeks. Baseline and 78-week magnetic resonance imaging (MRI) hippocampus volume (HV) measurements were conducted in a subgroup of patients. Results A total of 1,052 patients were enrolled and 790 (75.1%) completed the 78-week trial. Patient discontinuation and reasons for withdrawal were similar across groups. Planned analyses did not reveal statistically significant between-group differences. Lack of adequate statistical validity of the planned analysis models led to the development of revised predictive models. These adjusted models showed a trend toward a treatment effect for ADAS-cog (P = 0.098) and indicated significantly less HV loss for tramiprosate 100 mg (P = 0.035) and 150 mg (P = 0.009) compared to placebo. The incidence of adverse events was similar across treatment groups. Conclusions The primary planned analyses did not show a significant treatment effect, but were confounded by unexplained variance. Post-hoc analyses showed a significant treatment-related reduction in HV loss. However, there was only a trend towards slowing of decline on the ADAS-cog and no slowing of decline on the CDR-SB. These results must be interpreted in consideration of the limitations of clinical and

  14. A Randomized, Double-blind, Placebo-controlled Clinical Trial Evaluating an Oral Anti-aging Skin Care Supplement for Treating Photodamaged Skin

    PubMed Central

    Sigler, Monya L.; Hino, Peter D.; Moigne, Anne Le; Dispensa, Lisa

    2016-01-01

    Objective: Evaluate an anti-aging skin care supplement on the appearance of photodamaged skin. Design: Randomized, double-blind, placebo-controlled clinical trial. Following a one-month washout period, subjects received two anti-aging skin care formula tablets (total daily dose: marine complex 210mg, vitamin C 54mg, zinc 4mg) or placebo daily for 16 weeks. Subjects were restricted from products/procedures that may affect the condition/appearance of skin, including direct facial sun or tanning bed exposure. Participants utilized a standardized facial cleanser and SPF15 moisturizer. Setting: Single study center (Texas, United States; June-November 2007). Participants: Healthy women aged 35 to 60 years (mean, 50 years), Fitzpatrick skin type I-IV, modified Glogau type II—III. Measurements: Subjects were assessed at Weeks 6, 12, and 16 on clinical grading (0-10 VAS), bioinstrumentation, digital photography, and self-assessments. Analysis of variance with treatment in the model was used for between-group comparisons (alpha P≤0.05). Results: Eighty-two anti-aging skin care formula subjects and 70 placebo subjects completed the study. Significant differences in change from baseline to Week 16 scores were observed for clinical grading of overall facial appearance (0.26; P<0.0001), radiant complexion (0.59; P<0.0001), periocular wrinkles (0.08; P<0.05), visual (0.56; P<0.0001) and tactile (0.48; P<0.0001) roughness, and mottled hyperpigmentation (0.15; P<0.001) favoring the subjects in the anti-aging skin care supplement group. Ultrasound skin density (Week 16) was significantly reduced for placebo versus anti-aging skin care supplement group (-1.4% vs. 0%; P<0.01). Other outcomes were not significant. Mild gastrointestinal symptoms possibly related to the anti-aging skin care supplement (n=1) and placebo (n=2) were observed. Conclusion: Women with photodamaged skin receiving anti-aging skin care supplement showed significant improvements in the appearance of facial

  15. Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients with Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial

    PubMed Central

    Coggan, Andrew R.; Leibowitz, Joshua L.; Spearie, Catherine Anderson; Kadkhodayan, Ana; Thomas, Deepak P.; Ramamurthy, Sujata; Mahmood, Kiran; Park, Soo; Waller, Suzanne; Farmer, Marsha; Peterson, Linda R.

    2015-01-01

    Background Skeletal muscle strength, velocity, and power are markedly reduced in heart failure (HF) patients, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially due to decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with HF due to systolic dysfunction. Methods and Results Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in nine HF patients. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35–50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the two highest movement velocities tested (i.e., 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (i.e., 4.74±0.41 vs. 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher following NO3− ingestion (i.e., 12.48±0.95 vs. 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions In this pilot study, acute dietary NO3− intake was well-tolerated and enhanced NO bioavailability and muscle power in patients with systolic HF. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356. PMID:26179185

  16. Banha-sasim-tang as an herbal formula for the treatment of functional dyspepsia: a randomized, double-blind, placebo-controlled, two-center trial

    PubMed Central

    2010-01-01

    Background Functional dyspepsia (FD) is characterized by a high prevalence rate and no standard conventional treatments. Alternative therapies, such as herbal formulas, are widely used to treat FD. However, there are inadequate evidences regarding the safety and efficacy of these formulas. Moreover, the mechanisms by which herbal formulas act in the gastrointestinal tract are controversial. In traditional Korean medicine, Banha-sasim-tang has long been one of the most frequently prescribed herbal formulas for treating dyspepsia. The current study is designed to evaluate the efficacy and safety of Banha-sasim-tang for FD patients and to examine whether there will be a significant correlation between cutaneous electrogastrography recordings and dyspeptic symptoms in FD patients, and between changes in gastric myoelectrical activity and improvement in dyspeptic symptoms during Banha-sasim-tang administration. Methods This randomized, double-blind, placebo-controlled trial will be performed at two centers and will include a Banha-sasim-tang group and placebo group. Each group will consist of 50 FD patients. Six weeks of administration of Banha-sasim-tang or placebo will be conducted. During the subsequent 2 months, follow-up observations of primary and secondary outcomes will be performed. The primary outcomes are differences as measured on the gastrointestinal symptom scale, and the secondary outcomes are differences as measured on the visual analogue scale for dyspepsia and on the questionnaire for FD-related quality of life. All outcomes will be measured at baseline, at 2, 4, and 6 weeks of treatment, and at the 1 and 2 month follow-up. Cutaneous electrogastrography will be performed and assessed at baseline and at 6 weeks. Discussion This trial will provide evidence of the safety and efficacy of Banha-sasim-tang for the treatment for FD. Furthermore, based on the assessment of the relationship between cutaneous electrogastrography recordings and dyspeptic symptoms

  17. Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON

    PubMed Central

    Silva, Sandra Y; Rueda, Ligia C; Márquez, Gustavo A; López, Marcos; Smith, Daniel J; Calderón, Carlos A; Castillo, Juan C; Matute, Jaime; Rueda-Clausen, Christian F; Orduz, Arturo; Silva, Federico A; Kampeerapappun, Piyaporn; Bhide, Mahesh; López-Jaramillo, Patricio

    2007-01-01

    Background Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers. Methods and design A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two

  18. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

    PubMed Central

    2013-01-01

    Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. Methods Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. Results Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. Trial registration NIH website (http

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

    PubMed Central

    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 (< 5%). Conclusion: Participants with occasional disturbed sleep treated with gabapentin showed significantly longer sleep duration and greater depth (versus placebo) in response to a phase advance manipulation known to disrupt sleep maintenance. Citation: 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

  20. Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol® on glycemic control of subjects with impaired fasting glucose

    PubMed Central

    Evans, Malkanthi; Judy, William V; Wilson, Dale; Rumberger, John A; Guthrie, Najla

    2015-01-01

    Background This study investigated the efficacy of Diabetinol® in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. Subjects and methods Fifty subjects, aged 18–75 years, with fasting blood glucose ≤15.4 mmol/L, hemoglobin A1c levels ≤12%, and a body mass index between 25 and 40 kg/m2, were enrolled in a 24-week, randomized, double-blind, placebo-controlled, parallel study. Diabetinol® or placebo was administered as 2×525 mg capsules/day. Results In the Diabetinol® group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax) of serum glucose or area under the curve (AUC)0–240 minutes. The time to Cmax was longer for participants on Diabetinol® than placebo group at week 12 (P=0.01). Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol® group versus placebo. The Diabetinol® group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09) and 3.2 mg/dL at week 24 (P=0.41) over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol® group. Diabetinol® improved 6-month oral glucose tolerance test and 2-hour postprandial glucose profiles in participants between 40 and 60 years of age. Conclusion The current study suggests a role for Diabetinol® as an adjunctive therapy for glycemic maintenance and for decreasing the risk of diabetes

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

    PubMed Central

    Nagata, Eiichiro; Ogino, Mieko; Iwamoto, Kounosuke; Kitagawa, Yasuhisa; Iwasaki, Yasuo; Yoshii, Fumihito; Ikeda, Joh-E.

    2016-01-01

    Objective 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. Design A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial. Methods 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. Results 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. Conclusions 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. Trial Registration UMIN Clinical Trials UMIN000008527 PMID:26910108

  2. Effect of Deworming on Physical Fitness of School-Aged Children in Yunnan, China: A Double-Blind, Randomized, Placebo-Controlled Trial

    PubMed Central

    Yap, Peiling; Wu, Fang-Wei; Du, Zun-Wei; Hattendorf, Jan; Chen, Ran; Jiang, Jin-Yong; Kriemler, Susi; Krauth, Stefanie J.; Zhou, Xiao-Nong; Utzinger, Jürg; Steinmann, Peter

    2014-01-01

    Background There is considerable debate on the health impacts of soil-transmitted helminth infections. We assessed effects of deworming on physical fitness and strength of children in an area in Yunnan, People's Republic of China, where soil-transmitted helminthiasis is highly endemic. Methodology The double-blind, randomized, placebo-controlled trial was conducted between October 2011 and May 2012. Children, aged 9–12 years, were treated with either triple-dose albendazole or placebo, and monitored for 6 months post-treatment. The Kato-Katz and Baermann techniques were used for the diagnosis of soil-transmitted helminth infections. Physical fitness was assessed with a 20-m shuttle run test, where the maximum aerobic capacity within 1 min of exhaustive exercise (VO2 max estimate) and the number of 20-m laps completed were recorded. Physical strength was determined with grip strength and standing broad jump tests. Body height and weight, the sum of skinfolds, and hemoglobin levels were recorded as secondary outcomes. Principal Findings Children receiving triple-dose albendazole scored slightly higher in the primary and secondary outcomes than placebo recipients, but the difference lacked statistical significance. Trichuris trichiura-infected children had 1.6 ml kg−1 min−1 (P = 0.02) less increase in their VO2 max estimate and completed 4.6 (P = 0.04) fewer 20-m laps than at baseline compared to non-infected peers. Similar trends were detected in the VO2 max estimate and grip strength of children infected with hookworm and Ascaris lumbricoides, respectively. In addition, the increase in the VO2 max estimate from baseline was consistently higher in children with low-intensity T. trichiura and hookworm infections than in their peers with high-intensity infections of all soil-transmitted helminths (range: 1.9–2.1 ml kg−1 min−1; all P<0.05). Conclusions/Significance We found no strong evidence for significant improvements in physical fitness and

  3. The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebo-controlled, crossover study

    PubMed Central

    2013-01-01

    Background Anatabine (ANA), a minor tobacco alkaloid found in the Solanaceae family of plants, may exhibit anti-inflammatory activity, which may be useful to aid in recovery from exercise-induced muscle damage. The purpose of this study, therefore, was to examine the effects of ANA supplementation on the recovery of isometric strength and selected non-invasive indicators of muscle damage. Methods A double-blinded, placebo-controlled, crossover design was used to study eighteen men (mean ± SD age = 22.2 ± 3.1 yrs; body mass = 80.3 ± 15.7 kg) who participated in two randomly-ordered conditions separated by a washout period. The ANA condition consisted of consuming 6–12 mg anatabine per day for 10 days, while testing took place during days 7–10. The placebo (PLA) condition was identical except that the PLA supplement contained no ANA. Maximal voluntary isometric peak torque (PT) of the forearm flexors, arm circumference, hanging joint angle, and subjective pain ratings were measured before (PRE), immediately after (POST), and 24, 48, and 72 h after six sets of 10 maximal, eccentric isokinetic forearm flexion muscle actions. Resting heart rate and blood pressure were measured at PRE and 72 h in each condition. Results For PT, hanging joint angle, arm circumference, and subjective pain ratings, there were no condition x time (p > 0.05) interactions, there were no main effects for condition (p > 0.05), but there were main effects for time (p < 0.001). There were no condition x time (p > 0.05) interactions and no main effects for condition (p > 0.05) or time (p > 0.05) for blood pressure or resting heart rate. Conclusions ANA supplementation had no effect on the recovery of muscle strength, hanging joint angle, arm swelling, or subjective pain ratings after a bout of maximal eccentric exercise in the forearm flexors. Therefore, ANA may not be beneficial for those seeking to improve recovery from heavy eccentric

  4. A randomized, double-blind, placebo-controlled phase 2 pilot trial evaluating a novel, vaginal softgel capsule containing solubilized estradiol

    PubMed Central

    Pickar, James H.; Amadio, Julia M.; Hill, John M.; Bernick, Brian A.; Mirkin, Sebastian

    2016-01-01

    Abstract Objective: The aim of the study was to evaluate the safety and efficacy of vaginal estradiol (E2) softgel capsules for moderate-to-severe symptoms of vulvar and vaginal atrophy (VVA). Previous phase 1 studies showed lower systemic estrogen concentrations with this softgel capsule compared with an approved low-dose vaginal E2 tablet. Methods: In this randomized, double-blind, placebo-controlled phase 2 study, 50 postmenopausal women (aged 40-75 y) with at least1 moderate-to-severe VVA symptom received 10 μg vaginal E2 softgel capsules or placebo daily for 14 days. Changes from baseline in vaginal maturation index, investigator's assessment of vaginal mucosa (secretions, epithelial integrity, epithelial surface thickness, color), vaginal pH, and most bothersome symptom were assessed. Adverse events were evaluated. Results: Compared with placebo, the percentage of superficial (35.2 percentage points [pp] vs 8.75 pp; P = 0.0002) and intermediate (18.7 pp vs −3.54 pp; P = 0.0017) cells increased from baseline significantly more with vaginal E2 capsules, and parabasal cells decreased significantly more (−54.4 pp vs −4.80 pp; P < 0.0001). Vaginal pH decreased significantly more with vaginal E2 capsules (−0.974 vs −0.339; P = 0.0002). Decreases in severity of atrophic effects on vaginal epithelial integrity (−0.342 vs 0.176; P = 0.0001) and secretions (−0.643 vs −0.274; P = 0.0401) were significantly greater with vaginal E2 capsules vs placebo. There was no statistical difference in most bothersome symptom severity change from baseline. No serious adverse events were reported. Conclusions: Vaginal E2 softgel capsules are a safe, effective, local treatment option for postmenopausal women with moderate-to-severe VVA, with lower systemic estrogen absorption than currently available intravaginal treatments. PMID:26836245

  5. Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial

    PubMed Central

    van der Aa, M P; Elst, M A J; van de Garde, E M W; van Mil, E G A H; Knibbe, C A J; van der Vorst, M M J

    2016-01-01

    Background: As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied. Methods: In a randomized placebo-controlled double-blinded trial, 62 adolescents with obesity aged 10–16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months. Primary end points were change in body mass index (BMI) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Secondary end points were safety and tolerability of metformin. Other end points were body fat percentage and HbA1c. Results: Forty-two participants completed the 18-month study (66% girls, median age 13 (12–15) years, BMI 30.0 (28.3 to 35.0) kg m−2 and HOMA-IR 4.08 (2.40 to 5.88)). Median ΔBMI was +0.2 (−2.9 to 1.3) kg m−2 (metformin) versus +1.2 (−0.3 to 2.4) kg m−2 (placebo) (P=0.015). No significant difference was observed for HOMA-IR. No serious adverse events were reported. Median change in fat percentage was −3.1 (−4.8 to 0.3) versus −0.8 (−3.2 to 1.6)% (P=0.150), in fat mass −0.2 (−5.2 to 2.1) versus +2.0 (1.2–6.4) kg (P=0.007), in fat-free mass +2.0 (−0.1 to 4.0) versus +4.5 (1.3 to 11.6) kg (P=0.047) and in ΔHbA1c +1.0 (−1.0 to 2.3) versus +3.0 (0.0 to 5.0) mmol mol−1 (P=0.020) (metformin versus placebo). Conclusions: Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo. Therefore, metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance. PMID:27571249

  6. [The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study].

    PubMed

    Konrad, F; Schoenberg, M H; Wiedmann, H; Kilian, J; Georgieff, M

    1995-09-01

    Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury, sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAC) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. METHODS. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. RESULTS. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in

  7. The non-ergot derived dopamine agonist quinagolide in prevention of early ovarian hyperstimulation syndrome in IVF patients: a randomized, double-blind, placebo-controlled trial†

    PubMed Central

    Busso, Cristiano; Fernández-Sánchez, Manuel; García-Velasco, Juan Antonio; Landeras, José; Ballesteros, Augustín; Muñoz, Elkin; González, Sandra; Simón, Carlos; Arce, Joan-Carles; Pellicer, Antonio

    2010-01-01

    BACKGROUND Ovarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability. METHODS A randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 µg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17–21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset ≤9 days after hCG administration) in 182 IVF patients with ≥20 but less than 30 follicles ≥10 mm. RESULTS The incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 µg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09–0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10–0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide. CONCLUSIONS Quinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability. ClinicalTrials.gov Identifier: NCT00329693. PMID:20139430

  8. A Randomized, Double-Blind, Placebo-Controlled Study of Breath Powered Nasal Delivery of Sumatriptan Powder (AVP-825) in the Treatment of Acute Migraine (The TARGET Study)

    PubMed Central

    Cady, Roger K; McAllister, Peter J; Spierings, Egilius LH; Messina, John; Carothers, Jennifer; Djupesland, Per G; Mahmoud, Ramy A

    2015-01-01

    Objective To evaluate the efficacy and safety of AVP-825, a drug–device combination of low-dose sumatriptan powder (22 mg loaded dose) delivered intranasally through a targeted Breath Powered device vs an identical device containing lactose powder (placebo device) in the treatment of migraine headache. Background Early treatment of migraine headaches is associated with improved outcome, but medication absorption after oral delivery may be delayed in migraineurs because of reduced gastric motility. Sumatriptan powder administered with an innovative, closed-palate, Bi-Directional, Breath Powered intranasal delivery mechanism is efficiently absorbed across the nasal mucosa and produces fast absorption into the circulation. Results from a previously conducted placebo-controlled study of AVP-825 showed a high degree of headache relief with an early onset of action (eg, 74% AVP-825 vs 38% placebo device at 1 hour, P < .01). Methods In this double-blind, placebo-controlled, parallel-group study in adults with a history of migraine with or without aura, participants were randomized via computer-generated lists to AVP-825 or placebo device to treat a single migraine headache of moderate or severe intensity. The primary endpoint was headache relief (defined as reduction of headache pain intensity from severe or moderate migraine headache to mild or none) at 2 hours post-dose. Results Two hundred and thirty patients (116 AVP-825 and 114 placebo device) were randomized, of whom 223 (112 and 111, respectively) experienced a qualifying migraine headache (their next migraine headache that reached moderate or severe intensity). A significantly greater proportion of AVP-825 patients reported headache relief at 2 hours post-dose compared with those using the placebo device (68% vs 45%, P = .002, odds ratio 2.53, 95% confidence interval [1.45, 4.42]). Between-group differences in headache relief were evident as early as 15 minutes, reached statistical significance at 30

  9. Antihypertensive potential of combined extracts of olive leaf, green coffee bean and beetroot: a randomized, double-blind, placebo-controlled crossover trial.

    PubMed

    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.

  10. Effects of kivia powder on Gut health in patients with occasional constipation: a randomized, double-blind, placebo-controlled study

    PubMed Central

    2013-01-01

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

  11. The Effect of Cumin cyminum L. Plus Lime Administration on Weight Loss and Metabolic Status in Overweight Subjects: A Randomized Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Abedi, Fatemeh; Sharifi, Nasrin; Karamali, Fatemeh; Fakhrieh Kashan, Zohreh; Asemi, Zatollah

    2016-01-01

    Background Limited data are available regarding the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight subjects. Objectives The current study aimed to assess the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight. Patients and Methods This randomized double-blind placebo-controlled clinical trial was conducted on 72 subjects with overweight, aged 18 - 50 years old. Participants were randomly divided into three groups: Group A received high-dose Cumin cyminum L. and lime capsules (75 mg each, n = 24), group B low-dose Cumin cyminum L. and lime capsules (25 mg each, n = 24) and group C placebos (n = 24) twice daily for eight weeks. Results After eight weeks of intervention, compared with low-dose C. cyminum L. plus lime and placebo, taking high-dose C. cyminum L. plus lime resulted in significant weight loss (in the high-dose group: -2.1 ± 1.7 vs. in the low-dose group: -1.2 ± 1.5 and in the placebo group: + 0.2 ± 1.3 kg, respectively; P < 0.001) and body mass index (-0.8 ± 0.6 vs. -0.5 ± 0.5 and +0.1 ± 0.5 kg/m2, respectively; P < 0.001). In addition, administration of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo, led to a significant reduction in fasting plasma glucose (FPG) (P < 0.001) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (+ 0.02 ± 0.02 vs. + 0.01 ± 0.02 and 0.01 ± 0.01, respectively; P = 0.01). Moreover, a significant decrease in serum triglycerides (-14.1 ± 56.2 vs. +13.9 ± 36.8 and + 10.6 ± 25.1 mg/dL; respectively; P = 0.03), total-cholesterol (-18.4 ± 28.6 vs. +8.6 ± 28.5 and -1.0 ± 24.8 mg/dL; respectively; P = 0.004) and low density lipoproteins- (LDL)-cholesterol levels (-11.8 ± 20.7 vs. +6.5 ± 23.2 and -2.9 ± 20.4 mg/dL, respectively; P = 0.01) was observed following the consumption of

  12. The efficacy and tolerability of glucosamine sulfate in the treatment of knee osteoarthritis: A randomized, double-blind, placebo-controlled trial

    PubMed Central

    Giordano, Nicola; Fioravanti, Antonella; Papakostas, Panagiotis; Montella, Antonio; Giorgi, Giorgio; Nuti, Ranuccio

    2009-01-01

    Background: Osteoarthritis (OA) is the most common form of arthritis and is often associated with disability and impaired quality of life. Objective: The aim of the study was to assess the efficacy and tolerability of glucosamine sulfate (GS) in the treatment of knee OA. Methods: Consecutive outpatients affected by primary monolateral or bilateral knee OA were enrolled in this double-blind, double-dummy, prospective, randomized, placebo-controlled trial. One group received GS 1500 mg QD for 12 weeks, and the other group received placebo QD for 12 weeks. The treatment period was followed by a 12-week treatment-free observation phase. Each patient was examined at baseline and at weeks 4, 8, 12, 16, 20, and 24. The primary efficacy criteria were pain at rest and during movement, assessed on a visual analog scale (VAS) of 0 to 100 mm. The secondary criteria included the Western Ontario and McMaster Universities (WOMAC) index for total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). VAS, W-TPS, W-TSS, and W-TPFS were evaluated at baseline and at weeks 4, 8, 12, 16, 20, and 24. Analgesic drug consumption (ie, acetaminophen or NSAIDs) was also assessed. Results: Patient demographics were similar in the GS and placebo groups. Of 60 randomized patients (30 per group), 56 completed the study (28 treated with GS and 28 who received placebo). Statistically significant improvements in symptomatic knee OA were observed, as measured by differences in resting pain at weeks 8, 12, and 16 (all, P < 0.05 vs placebo) and in pain during movement at weeks 12 and 16 (both, P < 0.05). W-TPS was lower with GS than placebo at weeks 8, 12, and 16 (all, P < 0.01), and at week 20 (P < 0.05). W-TSS was also lower with GS than placebo at weeks 8, 12, 16, and 20 (all, P < 0.05). W-TPFS was lower with GS than placebo at weeks 8 (P < 0.05), 12 (P < 0.01), 16 (P < 0.05), and 20 (P < 0.05). Drug consumption was lower in the GS group than the placebo

  13. Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers

    PubMed Central

    2013-01-01

    Background UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. Methods This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. Results After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five

  14. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial

    PubMed Central

    2012-01-01

    Background Probiotics are an upcoming group of nutraceuticals claiming positive effects on athlete’s gut health, redox biology and immunity but there is lack of evidence to support these statements. Methods We conducted a randomized, double-blinded, placebo controlled trial to observe effects of probiotic supplementation on markers of intestinal barrier, oxidation and inflammation, at rest and after intense exercise. 23 trained men received multi-species probiotics (1010 CFU/day, Ecologic®Performance or OMNi-BiOTiC®POWER, n = 11) or placebo (n = 12) for 14 weeks and performed an intense cycle ergometry over 90 minutes at baseline and after 14 weeks. Zonulin and α1-antitrypsin were measured from feces to estimate gut leakage at baseline and at the end of treatment. Venous blood was collected at baseline and after 14 weeks, before and immediately post exercise, to determine carbonyl proteins (CP), malondialdehyde (MDA), total oxidation status of lipids (TOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Statistical analysis used multifactorial analysis of variance (ANOVA). Level of significance was set at p < 0.05, a trend at p < 0.1. Results Zonulin decreased with supplementation from values slightly above normal into normal ranges (<30 ng/ml) and was significantly lower after 14 weeks with probiotics compared to placebo (p = 0.019). We observed no influence on α1-antitrypsin (p > 0.1). CP increased significantly from pre to post exercise in both groups at baseline and in the placebo group after 14 weeks of treatment (p = 0.006). After 14 weeks, CP concentrations were tendentially lower with probiotics (p = 0.061). TOS was slightly increased above normal in both groups, at baseline and after 14 weeks of treatment. There was no effect of supplementation or exercise on TOS. At baseline, both groups showed considerably higher TNF-α concentrations than normal. After 14 weeks TNF-α was

  15. Schisandra chinensis fruit modulates the gut microbiota composition in association with metabolic markers in obese women: a randomized, double-blind placebo-controlled study.

    PubMed

    Song, Mi-young; Wang, Jing-hua; Eom, Taewoong; Kim, Hojun

    2015-08-01

    Schisandra chinensis fruit (SCF) is known to have beneficial effects on metabolic diseases, including obesity, and to affect gut microbiota in in vivo studies. However, in human research, there have been a few studies in terms of its clinical roles in lipid metabolism and modulation of gut microbiota. A double-blind, placebo-controlled study with 28 obese women with SCF or placebo was conducted for 12 weeks. Anthropometry and blood and fecal sampling were performed before and after treatment. Analysis of the gut microbiota in feces was performed using denaturing gradient gel electrophoresis and quantitative polymerase chain reaction. Although the values did not differ significantly between the 2 groups, the SCF group tended to show a greater decrease in waist circumference, fat mass, fasting blood glucose, triglycerides, aspartate aminotransferase, and alanine aminotransferase than the placebo group. Clustering of the denaturing gradient gel electrophoresis fingerprints for total bacteria before and after treatment indicated more separate clustering in SCF group than placebo. In correlation analysis, Bacteroides and Bacteroidetes (both increased by SCF) showed significant negative correlation with fat mass, aspartate aminotransferase, and/or alanine aminotransferase, respectively. Ruminococcus (decreased by SCF) showed negative correlation with high-density lipoprotein cholesterol and fasting blood glucose. In conclusion, administration of SCF for 12 weeks resulted in modulation of the gut microbiota composition in Korean obese women, and significant correlations with some bacterial genera and metabolic parameters were noted. However, in general, SCF was not sufficient to induce significant changes in obesity-related parameters compared with placebo.

  16. Rosa damascena oil improves SSRI-induced sexual dysfunction in male patients suffering from major depressive disorders: results from a double-blind, randomized, and placebo-controlled clinical trial

    PubMed Central

    Farnia, Vahid; Shirzadifar, Mehdi; Shakeri, Jalal; Rezaei, Mansour; Bajoghli, Hafez; Holsboer-Trachsler, Edith; Brand, Serge

    2015-01-01

    Background A substantial disadvantage of psychopharmacological treatment of major depressive disorder (MDD) with selective serotonin-reuptake inhibitors (SSRIs) is the impact on sexual dysfunction. The aim of the present study was to investigate whether the oil of Rosa damascena can have a positive influence on SSRI-induced sexual dysfunction (SSRI-I SD) of male patients who are suffering from MDD and are being treated with SSRIs. Method In a double-blind, randomized, and placebo-controlled clinical trial, a total of 60 male patients treated with an SSRI and suffering from MDD (mean age =32 years) and SSRI-I SD were randomly assigned to take either verum (R. damascena oil) or a placebo. Patients completed self-ratings of depression and sexual function at baseline, at 4 weeks later, and at the end of the study, 8 weeks after it started. Results Over time, sexual dysfunction improved more in the verum group than in the control group. Improvements were observed in the verum group from week 4 to week 8. Self-rated symptoms of depression reduced over time in both groups, but did so more so in the verum group than in the control group. Conclusion This double-blind, randomized, and placebo-controlled clinical trial showed that the administration of R. damascena oil ameliorates sexual dysfunction in male patients suffering from both MDD and SSRI-I SD. Further, the symptoms of depression reduced as sexual dysfunction improved. PMID:25834441

  17. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    PubMed

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  18. Schisandra chinensis fruit modulates the gut microbiota composition in association with metabolic markers in obese women: a randomized, double-blind placebo-controlled study.

    PubMed

    Song, Mi-young; Wang, Jing-hua; Eom, Taewoong; Kim, Hojun

    2015-08-01

    Schisandra chinensis fruit (SCF) is known to have beneficial effects on metabolic diseases, including obesity, and to affect gut microbiota in in vivo studies. However, in human research, there have been a few studies in terms of its clinical roles in lipid metabolism and modulation of gut microbiota. A double-blind, placebo-controlled study with 28 obese women with SCF or placebo was conducted for 12 weeks. Anthropometry and blood and fecal sampling were performed before and after treatment. Analysis of the gut microbiota in feces was performed using denaturing gradient gel electrophoresis and quantitative polymerase chain reaction. Although the values did not differ significantly between the 2 groups, the SCF group tended to show a greater decrease in waist circumference, fat mass, fasting blood glucose, triglycerides, aspartate aminotransferase, and alanine aminotransferase than the placebo group. Clustering of the denaturing gradient gel electrophoresis fingerprints for total bacteria before and after treatment indicated more separate clustering in SCF group than placebo. In correlation analysis, Bacteroides and Bacteroidetes (both increased by SCF) showed significant negative correlation with fat mass, aspartate aminotransferase, and/or alanine aminotransferase, respectively. Ruminococcus (decreased by SCF) showed negative correlation with high-density lipoprotein cholesterol and fasting blood glucose. In conclusion, administration of SCF for 12 weeks resulted in modulation of the gut microbiota composition in Korean obese women, and significant correlations with some bacterial genera and metabolic parameters were noted. However, in general, SCF was not sufficient to induce significant changes in obesity-related parameters compared with placebo. PMID:26048342

  19. Assessment of Denosumab in Korean Postmenopausal Women with Osteoporosis: Randomized, Double-Blind, Placebo-Controlled Trial with Open-Label Extension

    PubMed Central

    Koh, Jung-Min; Chung, Dong Jin; Chung, Yoon-Sok; Kang, Moo-Il; Kim, In-Ju; Min, Yong-Ki; Oh, Han-Jin; Park, Il Hyung; Lee, Yil-Seob; Waterhouse, Brian; Nino, Antonio; Fitzpatrick, Lorraine A.

    2016-01-01

    Purpose The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. Materials and Methods Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. Results Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. Conclusion Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women. PMID:27189284

  20. Efficacy of a natural mineral complex in North American adults with osteoarthritis of the knee: a randomized double-blind placebo-controlled study

    PubMed Central

    Evans, Malkanthi; Wilson, Dale; Guthrie, Najla

    2014-01-01

    Purpose This study evaluated the efficacy of a hydrothermal mineral complex (HMC) supplement in participants with knee osteoarthritis. Patients and methods This was a double-blind, placebo-controlled, 12-week crossover study with 150 participants receiving either placebo or HMC for 4 weeks, with a 4-week washout period. The primary endpoint was WOMAC™ pain, and secondary endpoints were WOMAC™ physical function and stiffness, the 36-Item Short Form Health Survey (SF-36), high-sensitivity C-reactive protein, tumor necrosis factor α, interleukin 6, and safety. Results There were no significant differences in WOMAC™ pain, stiffness, or physical function scores between groups. Within groups, subjects on both HMC and placebo reported improvements (P<0.001) in all WOMAC™ domains. HMC performed significantly better in total SF-36 scores (P=0.05) and physical function (P=0.02), and had improved total physical activity (P=0.06) and social functioning (P=0.09) scores compared with placebo. Within groups, physical function (P=0.01), limitations due to mental health/emotional well-being (P=0.02), bodily pain (P=0.001), and total physical (P=0.003) and mental health scores (P=0.02) improved in participants on HMC, whereas improvements in bodily pain (P=0.001), general health (P=0.01), and total physical activity (P=0.04) were reported in placebo. Subjects on HMC with body mass index (BMI) <25 kg/m2 showed a trend toward decreased pain scores (P=0.10), while pain increased in those administered placebo. Minimal clinically important improvement (MCII) in WOMAC™ pain scores increased from 28% of HMC-administered participants at week 2 to 41% at week 4, and decreased to 37% after 2 weeks of washout. In comparison, 41% of placebo-administered subjects achieved MCII by week 2 and week 4. A 10.4% greater increase in tumor necrosis factor α levels was seen in participants receiving placebo than those receiving HMC (P=0.07). There were no differences between groups in adverse

  1. A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

    ERIC Educational Resources Information Center

    Handen, Benjamin L.; Melmed, Raun D.; Hansen, Robin L.; Aman, Michael G.; Burnham, David L.; Bruss, Jon B.; McDougle, Christopher J.

    2009-01-01

    Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI…

  2. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Fallah Huseini, H; Amini, M; Mohtashami, R; Ghamarchehre, M E; Sadeqhi, Z; Kianbakht, S; Fallah Huseini, A

    2013-12-01

    Nigella sativa L. seeds (N. sativa) have been used as a traditional remedy for a wide range of diseases including hypertension. The present study was performed to explore the effects of N. sativa oil on blood pressure (BP) in healthy volunteers. In a double-blind, randomized study, 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were randomly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks. The systolic and diastolic BPs, body mass index and blood levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatinine and blood urea nitrogen were determined at baseline and endpoint. Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint. Other parameters did not significantly change in both groups at the endpoint. No adverse effects were reported. In conclusion, oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects.

  3. SHORT-TERM EFFICACY OF LOW-LEVEL LASER THERAPY IN PATIENTS WITH KNEE OSTEOARTHRITIS: A RANDOMIZED PLACEBO-CONTROLLED, DOUBLE-BLIND CLINICAL TRIAL

    PubMed Central

    Fukuda, Vanessa Ovanessian; Fukuda, Thiago Yukio; Guimarães, Márcio; Shiwa, Silvia; de Lima, Bianca Del Cor; Martins, Rodrigo Álvaro Brandão Lopes; Casarotto, Raquel Aparecida; Alfredo, Patrícia Pereira; Bjordal, Jan Magnus; Fucs, Patrícia Maria Moraes Barros

    2015-01-01

    Objective: This study was designed to evaluate the short-term efficacy of low-level laser therapy (LLLT) for improving pain and function in patients with knee osteoarthritis. Methods: Forty-seven patients with knee osteoarthritis (79 knees), of both genders, participated in this randomized controlled double-blind clinical trial. They were randomly allocated to two groups: laser group with 25 patients (41 knees) and placebo group with 22 patients (38 knees). LLLT was performed three times a week, totaling nine sessions, using a AsGa 904 nm laser with mean power of 60 mW and beam area of 0.5 cm2. Nine points were irradiated on the knee, with energy of 3.0 J/point. The placebo group was treated with the same laser device, but with a sealed probe. Evaluations using Lequesne, visual numerical scale (VNS), Timed Up and Go (TUG), goniometry and dynamometry were conducted before the treatment started and after the nine sessions of LLLT. Results: A significant improvement in pain and function was found in all the assessments applied to the laser group. On comparing the laser group with the placebo group, significant differences were found in the VNS-resting and Lequesne evaluations. Conclusion: Treatment with LLLT improves pain and function over the short term in patients with knee osteoarthritis. PMID:27027049

  4. Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial123

    PubMed Central

    Goldman, Barbara Davis; Fischer, Leslie M; da Costa, Kerry-Ann; Reznick, J Steven; Zeisel, Steven H

    2012-01-01

    Background: Choline is essential for fetal brain development, and it is not known whether a typical American diet contains enough choline to ensure optimal brain development. Objective: The study was undertaken to determine whether supplementing pregnant women with phosphatidylcholine (the main dietary source of choline) improves the cognitive abilities of their offspring. Design: In a double-blind, randomized controlled trial, 140 pregnant women were randomly assigned to receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18 wk gestation through 90 d postpartum. Their infants (n = 99) were tested for short-term visuospatial memory, long-term episodic memory, language development, and global development at 10 and 12 mo of age. Results: The women studied ate diets that delivered ∼360 mg choline/d in foods (∼80% of the recommended intake for pregnant women, 65% of the recommended intake for lactating women). The phosphatidylcholine supplements were well tolerated. Groups did not differ significantly in global development, language development, short-term visuospatial memory, or long-term episodic memory. Conclusions: Phosphatidylcholine supplementation of pregnant women eating diets containing moderate amounts of choline did not enhance their infants’ brain function. It is possible that a longer follow-up period would reveal late-emerging effects. Moreover, future studies should determine whether supplementing mothers eating diets much lower in choline content, such as those consumed in several low-income countries, would enhance infant brain development. This trial was registered at clinicaltrials.gov as NCT00678925. PMID:23134891

  5. Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study

    PubMed Central

    Cordes, Mareike; Coslovsky, Michael; Hanssen, Henner; Schmidt-Trucksäss, Arno; Donath, Marc Y.

    2015-01-01

    Exercise increases muscle derived Interleukin–6 (IL–6) leading to insulin secretion via glucagon-like peptide–1. IL–1 antagonism improves glycemia and decreases systemic inflammation including IL–6 in patients with type 2 diabetes. However, it is not known whether physiological, exercise-induced muscle-derived IL–6 is also regulated by the IL–1 system. Therefore we conducted a double blind, crossover study in 17 healthy male subjects randomized to receive either the IL–1 receptor antagonist IL-1Ra (anakinra) or placebo prior to an acute treadmill exercise. Muscle activity led to a 2–3 fold increase in serum IL–6 concentrations but anakinra had no effect on this exercise-induced IL–6. Furthermore, the IL–1 responsive inflammatory markers CRP, cortisol and MCP–1 remained largely unaffected by exercise and anakinra. We conclude that the beneficial effect of muscle-induced IL–6 is not meaningfully affected by IL–1 antagonism. Trial Registration ClinicalTrials.gov NCT01771445 PMID:26448147

  6. Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind, placebo-controlled clinical trial

    PubMed Central

    Hosseini, Azar; Mousavi, Seyed Hamed; Ghanbari, Anis; Homaee Shandiz, Fatemeh; Raziee, Hamid Reza; Pezeshki Rad, Masoud; Mousavi, Seyed Hadi

    2015-01-01

    Objective: Cancer represents the second cause of mortality in the world. Saffron as a medicinal plant is known for its anti-cancer and anti-depressant properties. In this randomized double blind clinical trial, the effects of saffron on response to treatment in patients suffering from liver metastasis were evaluated. Materials and Methods: Thirteen patients suffering from liver metastases who referred to Ghaem and Imam Reza hospital, Mashhad, Iran were included in this study and then divided into two different groups. Both groups received chemotherapy regimen. Patients in group one were treated with saffron capsule (50 mg, twice daily) during chemotherapy periods whereas patients in group two received placebo. A sum of the longest diameter were calculated and compared for all lesions in IV contrast CT scan before and after the treatment. Results: from 13 patients included in this study, six patients quit and seven continued until the end. In saffron-treated group, two patients showed partial and complete response (50%) whereas in placebo group, no response was seen. Also, two deaths in placebo and one in saffron group occurred. Conclusion: This research suggests that saffron might be useful in patients suffering from liver metastasis. However, further investigations with larger sample size are required. PMID:26468463

  7. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation.

    PubMed

    Mezzasalma, Valerio; Manfrini, Enrico; Ferri, Emanuele; Sandionigi, Anna; La Ferla, Barbara; Schiano, Irene; Michelotti, Angela; Nobile, Vincenzo; Labra, Massimo; Di Gennaro, Patrizia

    2016-01-01

    Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated. Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics. Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period. Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219. PMID:27595104

  8. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation

    PubMed Central

    Manfrini, Enrico; Ferri, Emanuele; La Ferla, Barbara; Schiano, Irene; Michelotti, Angela; Nobile, Vincenzo

    2016-01-01

    Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated. Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics. Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period. Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219.

  9. Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Nonopioid Analgesics on Pain following Arthroscopic Knee Surgery.

    PubMed

    Abdulla, Susanne; Eckhardt, Regina; Netter, Ute; Abdulla, Walied

    2012-01-01

    Purpose. In a randomized, double-blind trial, the efficacy of nonopioid analgesics on postoperative piritramide consumption was compared for pain relief during the first 24 h in patients recovering from arthroscopic knee surgery. Methods. 120 patients were treated with normal saline and/or one of the nonopioid analgesics (parecoxib, metamizole, paracetamol) in addition to piritramide using the PCA pump. Beginning in the postanesthesia care unit (PACU), patients were asked to quantify their pain experience at rest while piritramide consumption was recorded. Results. Piritramide consumption upon arrival in the PACU was high in all groups. However, cumulative consumption in the parecoxib group was significantly lower than that in the placebo group at 6 and 12 h after surgery. At discharge from the PACU, VAS scores dropped in all groups and were significantly lower in the parecoxib group. In the PACU, satisfaction of the patients was moderate and improved with time after surgery. Conclusions. There was statistically significant opioid-saving effect by administering parecoxib with better VAS scores and satisfaction level compared to placebo. The high pain score in the PACU in all groups immediately after recovering from remifentanil-based anesthesia would be prevented if local anesthetics were administered intra-articularly as part of a multimodal analgesic approach.

  10. Effect of pretreatment with acetaminophen on withdrawal movements associated with injection of rocuronium: a prospective, randomized, double-blind, placebo controlled study

    PubMed Central

    Jeon, Younghoon; Baek, Sung-Uk; Park, Sung Sik; Kim, Si Oh; Baek, Woon-Yi

    2010-01-01

    Background Withdrawal movement during rocuronium injection is a common, unresolved adverse effect. We aimed to investigate the effect of IV acetaminophen pretreatment on withdrawal movement during rocuronium injection. Methods This study enrolled 120 American Society of Anesthesiologists (ASA) I-II patients undergoing general anesthesia. They were randomly assigned to three treatment groups. After occluding venous drainage using a tourniquet on the upper arm, the saline group received 5 ml of 0.9% sodium chloride solution, the lidocaine group received 40 mg of lidocaine, and the acetaminophen group received 50 mg of acetaminophen. During injection of pretreatment drug, pain was assessed on a four-point scale. The tourniquet was released after 120 seconds and anesthesia was performed using thiopental sodium 5 mg/kg followed by rocuronium 0.6 mg/kg. The withdrawal movement was graded on a four-point scale in a double-blind manner. Results The incidence of pain on pretreatment injection in saline, lidocaine, and acetaminophen groups was 7.7%, 5.1%, and 2.5%, respectively. The incidence of withdrawal movements was 77.5% in saline group, 32.5% in lidocaine group, and 37.5% in acetaminophen group (P < 0.05). Conclusions Acetaminophen and lidocaine reduced the incidence of withdrawal movement after rocuronium injection compared with saline. PMID:20651992

  11. Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks

    PubMed Central

    Anekthananon, T.; Pukritayakamee, S.; Ratanasuwan, W.; Jittamala, P.; Werarak, P.; Charunwatthana, P.; Suwanagool, S.; Lawpoolsri, S.; Stepniewska, K.; Sapchookul, P.; Puthavathana, P.; Fukuda, C.; Lindegardh, N.; Tarning, J.; White, N. J.; Day, N.; Taylor, W. R. J.

    2013-01-01

    Objectives Long-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks. We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks. Methods We conducted a parallel group, double blind, 2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug-related (possibly, probably, definitely) serious or adverse events (AEs) graded ≥2. Results Recruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo. A total of 102 grade ≥2 AEs were reported or detected in 69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P = 0.26), and 23/131 (17.6%) versus 8/65 (12.3%) (P = 0.28). Intercurrent infections/fevers [26/102 (25.5%)], abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102 (17.6%)] were the most frequently reported AEs. There were no drug-related study withdrawals. Eight serious AEs were all due to intercurrent illnesses. Laboratory, lung function and ECG parameters were similar between drugs and placebos. Conclusions Oseltamivir and zanamivir were well tolerated in healthy hospital professionals. Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks. PMID:23143901

  12. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial.

    PubMed

    Schmid, B; Lüdtke, R; Selbmann, H K; Kötter, I; Tschirdewahn, B; Schaffner, W; Heide, L

    2001-06-01

    This study assessed the clinical efficacy of a chemically standardized willow bark extract in the treatment of osteoarthritis. Willow bark extract, in a dose corresponding to 240 mg salicin/day, was compared with placebo in a 2-week, double-blind, randomized controlled trial. The primary outcome measure was the pain dimension of the WOMAC Osteoarthritis Index. Secondary outcome measures included the stiffness and physical function dimensions of the WOMAC, daily visual analogue scales (VAS) on pain and physical function, and final overall assessments by both patients and investigators. A total of 78 patients (39 willow bark extract, 39 placebo) participated in the trial. A statistically significant difference between the active treatment and the placebo group was observed in the WOMAC pain dimension (d = 6.5 mm, 95% C.I. = 0.2-12.7 mm, p = 0.047); the WOMAC pain score was reduced by 14% from the baseline level after 2 weeks of active treatment, compared with an increase of 2% in the placebo group. The patient diary VAS confirmed this result, and likewise the final overall assessments showed superiority of the willow bark extract over the placebo (patients' assessment, p = 0.0002; investigators' assessment, p = 0.0073). It is concluded that the willow bark extract showed a moderate analgesic effect in osteoarthritis and appeared to be well tolerated.

  13. Milk-based cornstarch porridge fortified with iron is effective in reducing anemia: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Arcanjo, Francisco Plácido Nogueira; Arcanjo, Cecília Costa; Arcanjo, Francisco Carlos Nogueira; Campos, Lício de Albuquerque; Amancio, Olga Maria Silverio; Braga, Josefina Aparecida Pellegrini

    2012-10-01

    This study evaluates the impact of a milk-based cornstarch porridge fortified with iron, in 4-year olds, compared with control on hemoglobin levels and anemia prevalence. This trial was a cluster-randomized, double-blind one, and used milk-based cornstarch porridge fortified with 10 mg elemental iron (FeSO(4)), daily, during 14 weeks, compared with control. The study population comprised 4-year-old preschoolers (n = 131). Mean hemoglobin values at baseline were found to be 10.6 ± 0.61 g dl(-1) for intervention group, and after intervention 11.5 ± 0.80 g/dl, p < 0.0001. For control, mean hemoglobin values at baseline were 10.9 ± 0.53 g/dl, and after intervention 11.2 ± 0.73, p < 0.0001. The increase in mean hemoglobin was much greater in the intervention than in the control group, 0.86-0.26 g dl(-1), respectively (p < 0.0001). Anemia prevalence reduced from 75% to 20%, p < 0.0001, in the intervention group, with no reduction in the control group. Number needed for treatment was four. This study showed that milk-based cornstarch porridge fortified with ferrous sulfate increased hemoglobin levels and reduced anemia prevalence in 4-year-old preschoolers.

  14. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation

    PubMed Central

    Manfrini, Enrico; Ferri, Emanuele; La Ferla, Barbara; Schiano, Irene; Michelotti, Angela; Nobile, Vincenzo

    2016-01-01

    Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated. Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics. Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period. Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219. PMID:27595104

  15. Pretreatmet with 5% lidocaine patch reduces cannula-induced and propofol-induced pain: a randomized, double-blind, placebo-controlled study

    PubMed Central

    Hong, Jung-Min; Cho, Ah Reum; Baik, Ji Seok; Lee, Do Won; Ji, Young Tae; Yoo, Ki Chan; Kim, Hae-Kyu

    2016-01-01

    Background The purpose of this study was to determine the efficacy of 5% lidocaine patch in reducing propofol-induced pain and cannula-induced pain. Methods In a randomized, double-blind study, 126 patients were divided into one of three groups: pretreatment with a 5% lidocaine patch (Lidotop®) and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group A); pretreatment with a placebo patch and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group B); or pretreatment with a placebo patch and premixed 2 ml of 2% lidocaine (40 mg) with 1.5 mg/kg of 1% propofol (Group C) for induction of anesthesia. Pain severity was evaluated on a four-point verbal rating scale during intravenous cannulation, propofol injection, and 24 h after the operation (recall). Results Eighteen patients (47.4%) in Group A complained of cannula-induced pain compared with 35 (94.6%) in Group B and 36 (94.7%) in Group C (P < 0.001). Group A patients showed significantly lower incidence of propofol-induced pain and recall of propofol-induced pain compared with Group B (P < 0.001 and P = 0.01), whereas there was no difference compared with Group C. Conclusions Preoperative transdermal administration of 5% lidocaine patch is an effective and simple method in reducing propofol-induced pain as well as cannula-induced pain.

  16. A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of methamphetamine dependence.

    PubMed

    Johnson, Bankole A; Ait-Daoud, Nassima; Elkashef, Ahmed M; Smith, Edwina V; Kahn, Roberta; Vocci, Francis; Li, Shou-Hua; Bloch, Daniel A

    2008-02-01

    Methamphetamine dependence is an increasing public health problem in the United States. No efficacious medication for methamphetamine dependence has been developed. As ondansetron, a 5-HT3 receptor antagonist and modulator of cortico-mesolimbic dopamine function, has been shown to reduce some of the rewarding effects of d-amphetamine in animal and human laboratory studies, we decided to test whether it would be superior to placebo at reducing methamphetamine use. In a preliminary, multi-site, randomized, double-blind, 8-wk controlled trial, 150 methamphetamine-dependent men and women received ondansetron (0.25 mg, 1 mg, or 4 mg b.i.d.) or placebo. Participants were assessed on several measures of methamphetamine use including urine methamphetamine level up to three times per week. As a psychosocial adjunct to the medication condition, cognitive behavioural therapy also was administered three times per week. Ondansetron was well tolerated and was less likely than placebo to be associated with serious adverse events. Nevertheless, none of the ondansetron doses was superior to placebo at decreasing any of the measures of methamphetamine use, withdrawal, craving, or clinical severity of methamphetamine dependence. Our preliminary results do not support the utility of ondansetron, at the doses tested, as a treatment for methamphetamine dependence. These findings should be viewed in light of the possibility that a less intensive cognitive behavioural therapy regimen might have yielded more positive results in this initial phase II trial exploring for the efficacy of ondansetron.

  17. Effects of probiotics in patients with diabetes mellitus type 2: study protocol for a randomized, double-blind, placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Low grade chronic inflammation is observed in patients with type 2 diabetes mellitus (T2DM). Endotoxin derived from gut bacteria may act as a potent inflammatory stimulant. Probiotics, which are believed to contain health promoting live microorganisms, may influence circulating endotoxin levels. Ingestion of live probiotic cultures may alter gut microbiota in a beneficial manner to reduce inflammation; no information is available whether or not they do so in patients with T2DM. Therefore, the aim of this study is to characterize the beneficial effects of probiotics on circulating endotoxin levels and other biomarkers related to systemic low-grade inflammation in patients with T2DM. Methods One hundred and twenty consenting adult Saudi T2DM patients (naïve or newly diagnosed and without co-morbidities) will be enrolled in this clinical trial and randomized to receive daily placebo or probiotics (Ecologic®Barrier) for 26 weeks in a double-blind manner. Inflammatory and metabolic markers will be measured and fecal samples analyzed. Measurements/samples will be obtained at baseline and after 4, 8, 12/13 and 26 weeks of treatment. Discussion It is expected that the probiotic product will induce beneficial changes in gut microbiota, reduce the systemic inflammatory state through altering systemic endotoxin levels and, as such, reduce the systemic inflammatory response observed in T2DM subjects. Trial registration ClinicalTrials.gov Identifier: NCT01765517 PMID:23822518

  18. A parallel, randomized, double-blind, placebo-controlled study to investigate the effect of SagaPro on nocturia in men

    PubMed Central

    Geirsson, Gudmundur; Gudmundsdottir, Hrefna; Egilsdottir, Perla B.; Gudbjarnason, Sigmundur

    2013-01-01

    Objective. This study aimed to investigate the effect of SagaPro, a product derived from Angelica archangelica leaf, on nocturia. Material and methods. Sixty-nine male patients 45 years or older with at least two nocturnal voids were randomized to receive SagaPro or placebo in a double-blind design for 8 weeks. Voiding diaries were assessed before and after the treatment. Results. The results indicate that SagaPro is safe. The actual number of nocturnal voids (ANV), nocturnal polyuria index (NPi) and nocturnal bladder capacity index (NBC index) decreased in the test population, but there was no significant difference between the treatment groups. Subsequent subgroup analysis showed that SagaPro significantly reduced the NBC index and nocturnal voids per sleeping hour in comparison to the placebo in participants with baseline NBC index above 1.3. When participants with sleep disorders were excluded from this group, ANV was also significantly reduced for the SagaPro group in comparison to the placebo group. Conclusion. SagaPro, made from an extract of the medicinal herb Angelica archangelica, is safe. This study did not show that SagaPro improved nocturia overall compared to placebo. Subgroup analysis suggested a beneficial effect in individuals with decreased nocturnal bladder capacity, which warrants further study. PMID:23323790

  19. A randomized, double-blind, placebo-controlled, cross-over study to evaluate analgesic activity of Terminalia chebula in healthy human volunteers using a mechanical pain model

    PubMed Central

    Pokuri, Venkata Kishan; Kumar, Chiranjeevi Uday; Pingali, Usharani

    2016-01-01

    Background and Aims: To evaluate analgesic activity and safety of single oral dose (1000 mg) of Terminalia chebula using a mechanical pain model in healthy human volunteers. Material and Methods: Twelve healthy volunteers were randomized to receive either single oral dose of 2 capsules of T. chebula 500 mg each or identical placebo capsules in a double-blinded manner. Mechanical pain was assessed using Ugo basile analgesy meter (Randall–Selitto test) before and 3 h after administration of test drug. The parameters evaluated were pain threshold force and time; pain tolerance force and time. A washout period of 1-week was given for crossover between active drug and placebo. Results: Terminalia chebula significantly increased the mean percentage change for pain threshold force and time, and pain tolerance force and time compared to placebo (P < 0.001). The mean percentage change for pain threshold force and time (20.8% and 21.0%) was increased more than that of pain tolerance force and time (13.4% and 13.4%). No adverse drug reaction was reported with either of the study medications during the study period. Conclusion: T. chebula significantly increased pain threshold and pain tolerance compared to placebo. Both the study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug in patients suffering from osteoarthritis, rheumatoid arthritis and other painful conditions. PMID:27625480

  20. Comparison of the Anti-Adhesion Activity of Three Different Cranberry Extracts on Uropathogenic P-fimbriated Escherichia coli: a Randomized, Double-blind, Placebo Controlled, Ex Vivo, Acute Study.

    PubMed

    Howell, Amy; Souza, Dan; Roller, Marc; Fromentin, Emilie

    2015-07-01

    Research suggests that cranberry (Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine. from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo. PMID:26411014

  1. Comparison of the Anti-Adhesion Activity of Three Different Cranberry Extracts on Uropathogenic P-fimbriated Escherichia coli: a Randomized, Double-blind, Placebo Controlled, Ex Vivo, Acute Study.

    PubMed

    Howell, Amy; Souza, Dan; Roller, Marc; Fromentin, Emilie

    2015-07-01

    Research suggests that cranberry (Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine. from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo.

  2. Efficacy and safety of extract of Ginkgo biloba as an adjunct therapy in chronic schizophrenia: A systematic review of randomized, double-blind, placebo-controlled studies with meta-analysis.

    PubMed

    Chen, Xichuang; Hong, Yuan; Zheng, Panpan

    2015-07-30

    Our study was to review and evaluate the efficacy and safety of extract of Gb (EGb) as an adjuvant therapy to antipsychotics in chronic schizophrenia treatment. We searched Pubmed/Medline, Embase, PsycINFO, the Cochrane library, and especially the Chinese periodical databases. Finally, eight randomized, double-blind, placebo-controlled trials (RCTs) of 1033 patients were enrolled, with 571 cases in EGb group and 462 in placebo. The result showed that EGb had a significant difference in ameliorating total and negative symptoms of chronic schizophrenia as an adjuvant therapy to antipsychotics. Thus, the EGb therapy plus antipsychotics might be more efficacious. Although the studies describing adverse reactions showed no distinguishable difference between EGb and placebo group in mean total scores of Treatment Emergent Symptom Scale (TESS) or a Rating Scale for Extrapyramidal Side Effects (RSESE), the results of subscores varied in different studies. In addition, the severity of side effects of EGb might be related to its daily dosage. Therefore, the safety of EGb therapy in chronic schizophrenia treatment might need more evidence. And all of these eight trials were carried out in China; thus, the results might be restricted to the race and we need more high-quality studies of multi-center and randomized double-blind clinical trials to compare, analyze, and confirm the findings further.

  3. A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of STA-2 (Green Tea Polyphenols) in Patients with Chronic Stable Angina

    PubMed Central

    Lee, Tsung-Ming; Charng, Min-Ji; Tseng, Chuen-Den; Lai, Ling-Ping

    2016-01-01

    Background Green tea intake has been shown to improve endurance capacity in animal studies, but whether it has a similar effect on humans remains unclear. A randomized, double-blinded, parallel-controlled study was conducted to evaluate the short-term effect of STA-2, a pharmaceutical preparation of green tea polyphenols, in patients with effort-induced angina and documented positive exercise tolerance test. Methods A total of 79 patients recruited from three medical centers were randomly assigned to receive 2 STA-2 250 mg capsules, each containing 100 mg green tea polyphenols, three times daily, or placebo for six weeks after two consecutive symptom-limited treadmill exercise tests to ascertain the reproducibility of exercise tolerance. Results There was no difference in total exercise tolerance time from baseline to Week 6 between two groups (p = 0.639). There were also no observed improvements in subgroup analyses stratified by age, gender, and BMI categories. However, a significant reduction in low-density lipoprotein levels was shown in patients in the STA-2 group (-8.99 ± 19.18 mg/dL) versus the placebo group (0.57 ± 19.77 mg/dL), p = 0.037, with greater benefits in patients not taking antihyperlipidemic drugs (STA-2: -9.10 ± 19.96 mg/dL vs. placebo: 4.42 ± 15.08 mg/dL, p = 0.037). Conclusions STA-2 treatment for 6 weeks did not increase exercise time as measured on a treadmill. However, this study also indicated that STA-2 treatment could have potential beneficial effects on LDL-cholesterol concentrations. PMID:27471357

  4. The effect of dry needling in the treatment of myofascial pain syndrome: a randomized double-blinded placebo-controlled trial.

    PubMed

    Tekin, Levent; Akarsu, Selim; Durmuş, Oğuz; Cakar, Engin; Dinçer, Umit; Kıralp, Mehmet Zeki

    2013-03-01

    The objective of this study was to test the hypothesis that dry needling is more effective than sham dry needling in the treatment of myofascial pain syndrome (MPS). This was a prospective, double-blinded, randomized-controlled study conducted in an outpatient clinic. Thirty-nine subjects with established myofascial trigger points were randomized into two groups: study group (N = 22) and placebo group (N = 17). Dry needling was applied using acupuncture needles, and sham dry needling was applied in the placebo group. The treatment was composed of six sessions which were performed in 4 weeks; the first four sessions were performed twice a week (for 2 weeks) and the last two, once a week (for 2 weeks). The visual analog scale (VAS) and Short Form-36 (SF-36) were used. When compared with the initial values, VAS scores of the dry needling group following the first and sixth sessions were significantly lower (p = 0.000 and p < 0.000, respectively). When VAS scores were compared between the groups, the first assessment scores were found to be similar, but the second and third assessment scores were found to be significantly lower in the dry needling group (p = 0.034 and p < 0.001, respectively). When SF-36 scores of the groups were compared, both the physical and mental component scores were found to be significantly increased in the dry needling group, whereas only those of vitality scores were found to be increased significantly in the placebo (sham needling) group. The present study shows that the dry needling treatment is effective in relieving the pain and in improving the quality of life of patients with MPS.

  5. Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial

    PubMed Central

    Ayatollahi, Vida; Behdad, Shekoufeh; Hatami, Maryam; Moshtaghiun, Hossein; Baghianimoghadam, Behnam

    2012-01-01

    Aim To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects. Methods The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery. Results Tramadol group had significantly lower pain scores (P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting. Conclusion Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects. Registration No: IRCT201103255764N2 PMID:22522994

  6. The Efficacy of Oral Melatonin in Improving Sleep in Cancer Patients with Insomnia: A Randomized Double-Blind Placebo-Controlled Study

    PubMed Central

    Kurdi, Madhuri S; Muthukalai, Sindhu Priya

    2016-01-01

    Background: The natural hormone melatonin has sleep inducing properties. Insomnia in cancer patients is common. So far, melatonin has been seldom tried for the improvement of sleep in patients with malignancies. Keeping this in mind, we planned and conducted a double-blind study to test the efficacy of melatonin in promoting sleep in patients with malignancies suffering from insomnia. Objective: To assess the hypnotic efficacy of oral melatonin in cancer patients with insomnia. Materials and Methods: After Ethical Committee approval, 50 patients (age range 20-65 years) from our pain clinic NIVARANE who met the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria for primary insomnia were randomized to receive melatonin 3 mg or placebo at 7 pm orally every day for 14 days from our pharmacist. After 1, 7, 14 days, the patients were reviewed with the Athens insomnia scale oral questionnaire to document the subjective sleep quality. The patients and we, the investigators were blinded to the study drug. Results: There were 2 drop outs (one from each group) as they failed to complete visit on day 14. Significant differences in favor of melatonin treatment were found in clinically relevant improvements in insomnia (46.53%; P = 0.00001 vs. 11.30%; P = 0.1026) There was improvement in sleep from 1 to 7 days (19.91%; P = 0.00001 vs. 0.98%; P = 0.2563). More significant improvements were seen between 7 and 14 days (33.24%; P = 0.00001 vs. 10.42%; P = 0.1469). Conclusion: We conclude that daily intake of oral melatonin 2 h before bedtime improves sleep induction and quality in cancer patients with insomnia. PMID:27559258

  7. Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: a randomized, double blind, placebo-controlled study.

    PubMed

    Barker, Tyler; Rogers, Victoria E; Levy, Mark; Templeton, Jenna; Goldfine, Howard; Schneider, Erik D; Dixon, Brian M; Henriksen, Vanessa T; Weaver, Lindell K

    2015-02-01

    The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m(2); serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n=15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n=14) or (3) 8000IU (n=17). Supplements were taken daily for 35days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000IU, ≈29%; 8000IU, ≈57%) and 1,25(OH)D (4000IU, ≈12%; 8000IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n=31) were dependent on initial levels as serum 25(OH)D (r=-0.63, p<0.05) and 1,25(OH)D (r=-0.45, p<0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D<29ng/mL) compared to sufficient (serum 25(OH)D⩾30ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D. PMID:25461390

  8. Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis.

    PubMed

    Salmhofer, W; Maier, H; Soyer, H P; Hönigsmann, H; Hödl, S

    2000-01-01

    A double-blind, randomized clinical study was conducted to compare the efficacy and tolerability of twice-daily topical calcipotriol treatment with a combination treatment of calcipotriol once a day in the morning and diflucortolone valerate in the evening. Sixty-three patients with a clinical diagnosis of chronic plaque psoriasis and comparable psoriatic lesions on both sides of the body were included. After a washout phase of 1 week, psoriatic lesions were treated for 4 weeks with calcipotriol ointment twice daily on one side of the body and a combination of calcipotriol and diflucortolone valerate ointment on the other side. The treatment period was followed by a period of 4 weeks without any treatment. The psoriasis area and severity index (PASI) was used to compare the 2 groups. Furthermore, the overall therapeutic results were assessed independently by the investigators and by the patients. Both treatment regimens showed a significant, nearly identical, reduction in PASI. The mean PASI for calcipotriol alone was 5.7 at baseline, 1.9 after 4 weeks of treatment and 3.8 at the end of the follow-up period. For combination therapy, these values were 5.7, 1.8 and 3.8, respectively. There was a statistically significant advantage in favor of combined calcipotriol and diflucortolone valerate treatment at weeks 1 and 2 (p < 0.05); however, at the end of the treatment phase the difference between the 2 therapies was not significant. Subjective evaluation of efficacy by both the investigators and the patients revealed no difference between the 2 treatments. The frequency of side effects (e.g. irritation) was low in both groups. In conclusion, both therapies were effective for the treatment of chronic plaque-type psoriatic lesions. The combination of calcipotriol and a topical steroid appeared to produce a more rapid clinical response and was shown to be as effective as calcipotriol therapy alone. PMID:11234559

  9. Acetaminophen for self-reported sleep problems in an elderly population (ASLEEP): study protocol of a randomized placebo-controlled double-blind trial

    PubMed Central

    2014-01-01

    Background The prevalence of sleep disorders increases with age. Sleep disorders may have serious health implications and may be related to serious underlying diseases. Many older people use hypnotics, like benzodiazepines, although these medications have serious side effects and often lead to habituation. Acetaminophen is one of the most frequently used off-label drugs for sleep disorders, although little is known about its effects. Our objective is to investigate whether acetaminophen is effective in treating self-reported sleep disorders in older people. Methods/Design Participants, aged 65 years or older (n = 150), who have sleep disorders will be randomized for treatment with either acetaminophen 1000 mg or placebo, once daily at bedtime in a double-blind design. Eligible patients should be able to give informed consent, should not be cognitively impaired (Minimal Mental State Examination (MMSE) score ≥ 20), should not have pain, and should not use acetaminophen on a regular basis because of pain complaints. The study will take three weeks to complete. During these three weeks, the participants register their sleep behavior in a sleep diary. The participants will use the study medication during the second and third week. The primary endpoint will be the self-reported sleep disorders at the end of week three, as measured by means of the Insomnia Severity Index (ISI). To validate these subjective sleep parameters against objectively measured indices of the sleep-wake pattern, we will measure the periods of wakefulness and sleep in a subgroup of participants, using an actigraph worn on the wrist during the entire study period. Discussion The proposed study will contribute to our knowledge about the treatment of sleep disorders in an older population. There is a need for treatments for sleep disorders without serious adverse effects. Acetaminophen might be a simple and inexpensive alternative for the regimes that are currently used with older people

  10. A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

    ERIC Educational Resources Information Center

    Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

    2009-01-01

    A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

  11. A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.

    PubMed

    Coronel, Jaime; Cetina, Lucely; Pacheco, Irlanda; Trejo-Becerril, Catalina; González-Fierro, Aurora; de la Cruz-Hernandez, Erick; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Arias-Bofill, Daymi; Candelaria, Myrna; Vidal, Silvia; Dueñas-González, Alfonso

    2011-12-01

    The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.

  12. Therapeutic efficacy of traditional Chinese medicine, Shen-Mai San, in cancer patients undergoing chemotherapy or radiotherapy: study protocol for a randomized, double-blind, placebo-controlled trial

    PubMed Central

    2012-01-01

    Background Cancer is one of the major health issues worldwide. An increasing number of cancer patients are offered treatment with surgery, chemotherapy and radiotherapy. Traditional Chinese medicine (TCM) is one of the most common complementary therapies offered to cancer patients in Taiwan. We designed a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of TCM in patients with cancer. Methods/design In this study, inclusion criteria are postoperative patients with histologically confirmed cancer within 3 years who are undergoing chemotherapy or radiotherapy, more than 18 years old, have given signed informed consent, have the ability to read Chinese, and the ability for oral intake. Exclusion criteria include being pregnant, breast feeding, having completed chemotherapy or radiotherapy, brain metastasis with Eastern Cooperative Oncology Group (ECOG) performance status of two to four, delusion or hallucinations, acute infection, and have received medications under other clinical trials. The patients were separated into an intervention group (Shen-Mai-San, SMS) and a placebo group for four weeks using a randomized, double-blind procedure. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QOL-C30) was used to evaluate the quality of life. General data, hemoglobin (Hb), hematocrit (Hct), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine, carcinoembryonic antigen (CEA), TCM diagnosis data and heart rate variability (HRV) were also recorded. These data were collected at baseline, two weeks and four weeks after receiving medication. The patients were prescribed granules which contained therapeutic medicines or placebo. Paired-T test was used for statistical analysis. Discussion Shen-Mai-San is composed of processed Ginseng radis, Liriope spicata, and Schizandrae fructus. It was found to be effective for treating cancer

  13. Lithium as add-on to quetiapine XR in adult patients with acute mania: a 6-week, multicenter, double-blind, randomized, placebo-controlled study.

    PubMed

    Bourin, Michel S; Severus, Emanuel; Schronen, Juan P; Gass, Peter; Szamosi, Johan; Eriksson, Hans; Chandrashekar, Hongally

    2014-01-01

    Quetiapine extended release (XR) and lithium are treatments with proven efficacy in acute mania. This randomized study evaluated the efficacy and safety of lithium or placebo as add-on to quetiapine XR in adult patients with manic or mixed symptoms of bipolar I disorder. In this 6-week, double-blind study (Trial D144AC00003), adult patients with DSM-IV-TR-diagnosed bipolar I disorder (current episode manic or mixed), a Young Mania Rating Scale (YMRS) total score ≥20, and score ≥4 on two of four core YMRS items were administered quetiapine XR (400 to 800 mg/day) and randomly assigned to receive add-on lithium (600 to 1,800 mg/day) or placebo. The primary efficacy end point was change in the YMRS total score from baseline to day 43, analyzed using a mixed-model for repeated measures (MMRM) approach. Secondary efficacy and safety end points were also measured. Rating scales were administered by trained staff. Three hundred fifty-six patients treated with quetiapine XR were randomized to add-on lithium (n = 173) or placebo (n = 183). Two hundred ninety-one patients (81.7%) completed the study. At day 43, least squares mean change in YMRS total score was -22.8 for add-on lithium and -20.1 for add-on placebo, a statistically significant treatment group difference of -2.69 (p < 0.001). On secondary measures, add-on lithium was associated with significant improvements in response, remission, illness severity, and overall illness versus add-on placebo (p < 0.05). The number needed to treat was 9.1 for response and 7.9 for remission for add-on lithium compared with add-on placebo. Lithium in combination with quetiapine XR was generally well tolerated, with a similar profile to quetiapine XR in combination with placebo. The addition of lithium to quetiapine XR therapy was associated with significantly greater efficacy than placebo as add-on and was generally well tolerated in patients with acute bipolar I mania. This study was registered under Clinicaltrials

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  15. A Single Dose of Amoxicillin and Dexamethasone for Prevention of Postoperative Complications in Third Molar Surgery: A Randomized, Double-Blind, Placebo Controlled Clinical Trial

    PubMed Central

    Bortoluzzi, Marcelo Carlos; Capella, Diogo Lenzi; Barbieri, Tharzon; Pagliarini, Micheli; Cavalieri, Talita; Manfro, Rafael

    2013-01-01

    Background The aim of this study was to assess the efficacy of a single prophylactic dose of amoxicillin and/or dexamethasone in preventing postoperative complications (PC) after a surgical removal of a single mandibular third molar (M3). Methods This study is a randomized, placebo controlled clinical trial. Four groups were included: Group 1 (G1) included a prophylactic dose of 2 g of amoxicillin and 8 mg of dexamethasone; Group 2 (G2) included a prophylactic dose of 2 g of amoxicillin and 8 mg of placebo; Group 3 (G3) included a prophylactic dose of 8 mg of dexamethasone and 2 g of placebo and; Group 4 (G4) placebo. Results Fifty patients were included. It was observed one case of alveolar infection (2%) and two of alveolar osteitis (4%) resulting in three PC (6%). No statistical differences were observed between therapeutic groups for development of PC, trismus, pain and edema. The use of antibiotics showed an absolute risk reduction (ARR) for PC development of 3.52% and the number needed to treat (NNT) was 29. Conclusion Prophylactic antibiotics and corticoid in a single dose regimen did not bring any benefit on M3 surgeries. PMID:23390473

  16. A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis

    PubMed Central

    Moustafa, Moustafa; Lehrner, Lawrence; Al-Saghir, Fahd; Smith, Mark; Goyal, Sunita; Dillon, Maureen; Hunter, John; Holmes-Farley, Randy

    2014-01-01

    Background Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed. Methods A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL) hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed. Results Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in phosphorus lowering per gram of binder compared with sevelamer carbonate. Overall toler-ability was similar between active treatment groups. The tolerability of sevelamer carbonate was consistent with prior studies and with the established safety profile of sevelamer. Conclusion Both Genz-644470 and sevelamer carbonate effectively lowered serum phosphate levels in a dose-dependent fashion in patients with chronic kidney disease on

  17. SMA CARNI-VAL Trial Part I: Double-Blind, Randomized, Placebo-Controlled Trial of L-Carnitine and Valproic Acid in Spinal Muscular Atrophy

    PubMed Central

    Swoboda, Kathryn J.; Scott, Charles B.; Crawford, Thomas O.; Simard, Louise R.; Reyna, Sandra P.; Krosschell, Kristin J.; Acsadi, Gyula; Elsheik, Bakri; Schroth, Mary K.; D'Anjou, Guy; LaSalle, Bernard; Prior, Thomas W.; Sorenson, Susan L.; Maczulski, Jo Anne; Bromberg, Mark B.; Chan, Gary M.; Kissel, John T.

    2010-01-01

    Background Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo. Methods Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of “sitters” (cohort 1) and an ambulatory group of “walkers” (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2–8 years of age. Sixty-one subjects were randomized 1∶1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures. Results At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = −1.22–2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007). Conclusions This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age

  18. Acute, short- and long-term efficacy of oral bevantolol in patients with coronary artery disease: a placebo-controlled, randomized, double-blind study.

    PubMed

    Gimeno, J V; Ferrer, J; Olague, J; Bordes, P; Serra, J; Estruch, G; Mainer, V; Algarra, F J

    1986-09-01

    The efficacy and safety of bevantolol (new cardioselective beta-blocking agent without intrinsic sympathetic activity) were evaluated in chronic stable angina pectoris. Acute effects on heart rate (HR) and pulmonary function (forced expiratory volume in the first second, FEV1, and vital capacity, VC) (double-blind placebo, propranolol, 80 mg, and bevantolol, 150 mg) and the antianginal efficacy during early (double-blind placebo period) and chronic bevantolol therapy (long-term follow-up for 52 weeks) were studied. Bevantolol reduces HR in the same way as propranolol (both p less than 0.01). Pulmonary function is modified significantly only by propranolol (decreasing FEV1, p less than 0.05). Bevantolol reduces antianginal attacks and nitroglycerin consumption (p less than 0.01) and improves exercise tolerance (p less than 0.01) during early and chronic therapy.

  19. Acute, short- and long-term efficacy of oral bevantolol in patients with coronary artery disease: a placebo-controlled, randomized, double-blind study.

    PubMed

    Gimeno, J V; Ferrer, J; Olague, J; Bordes, P; Serra, J; Estruch, G; Mainer, V; Algarra, F J

    1986-09-01

    The efficacy and safety of bevantolol (new cardioselective beta-blocking agent without intrinsic sympathetic activity) were evaluated in chronic stable angina pectoris. Acute effects on heart rate (HR) and pulmonary function (forced expiratory volume in the first second, FEV1, and vital capacity, VC) (double-blind placebo, propranolol, 80 mg, and bevantolol, 150 mg) and the antianginal efficacy during early (double-blind placebo period) and chronic bevantolol therapy (long-term follow-up for 52 weeks) were studied. Bevantolol reduces HR in the same way as propranolol (both p less than 0.01). Pulmonary function is modified significantly only by propranolol (decreasing FEV1, p less than 0.05). Bevantolol reduces antianginal attacks and nitroglycerin consumption (p less than 0.01) and improves exercise tolerance (p less than 0.01) during early and chronic therapy. PMID:3530572

  20. Efficacy of Grintuss® pediatric syrup in treating cough in children: a randomized, multicenter, double blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Cough is an extremely common problem in pediatrics, mostly triggered and perpetuated by inflammatory processes or mechanical irritation leading to viscous mucous production and increased sensitivity of the cough receptors. Protecting the mucosa might be very useful in limiting the contact with micro-organisms and irritants thus decreasing the inflammation and mucus production. Natural molecular complexes can act as a mechanical barrier limiting cough stimuli with a non pharmacological approach but with an indirect anti-inflammatory action. Objective Aim of the study was to assess the efficacy of a medical device containing natural functional components in the treatment of cough persisting more than 7 days. Methods In this randomized, parallel groups, double-blind vs. placebo study, children with cough persisting more than 7 days were enrolled. The clinical efficacy of the study product was assessed evaluating changes in day- and night-time cough scores after 4 and 8 days (t4 and t8) of product administration. Results In the inter-group analysis, in the study product group compared with the placebo group, a significant difference (t4 study treatment vs. t4 placebo, p = 0.03) was observed at t4 in night-time cough score. Considering the intra-group analysis, only the study product group registered a significant improvement from t0 to t4 in both day-time (t0 vs. t4, p = 0.04) and night-time (t0 vs. t4, p = 0.003) cough scores. A significant difference, considering the study product, was also found in the following intra-group analyses: day-time scores at t4 vs. t8 (p =0.01) and at t0 vs. t8 (p = 0.001); night-time scores at t4 vs. t8 (p = 0.05), and at t0 vs. t8 (p = 0.005). Considering a subgroup of patients with higher cough (≥3) scores, 92.9% of them in the study product group improved at t0 vs. t4 day-time. Conclusions Grintuss® pediatric syrup showed to possess an interesting profile of efficacy and safety in the treatment

  1. Efficacy and safety of duloxetine in the treatment of older adult patients with generalized anxiety disorder: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    Alaka, Karla J; Noble, William; Montejo, Angel; Dueñas, Héctor; Munshi, Autar; Strawn, Jeffrey R; Lenox-Smith, Alan; Ahl, Jonna; Bidzan, Leszek; Dorn, Brita; Ball, Susan

    2014-01-01

    Objective This was a flexible-dosed study to evaluate the efficacy and safety of duloxetine 30–120 mg once daily in the treatment of generalized anxiety disorder (GAD) in older adult patients. Methods Patients with GAD, who were at least 65 years of age, were randomly assigned to double-blind treatment with either duloxetine (N = 151) or placebo (N = 140). The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) total score, and the primary endpoint was at week 10. Global functioning was assessed by the Sheehan Disability Scale (SDS). Safety and tolerability was assessed by the occurrence of treatment-emergent adverse events, serious adverse events, laboratory analyses, and vital signs. Analyses were conducted on an intent-to-treat basis. Results The overall baseline mean HAM-A total score was 24, and SDS global score was 14. Completion rates were 75% for placebo and 76% for duloxetine. At week 10, duloxetine was superior to placebo on mean changes from baseline in HAM-A total scores (−15.9 vs. −11.7, p < 0.001) and in SDS global scores (−8.6 vs. −5.4, p < 0.001). Treatment-emergent adverse events occurred in ≥5% of duloxetine-treated patients and twice the rate than with placebo including constipation (9% vs. 4%, p = 0.06), dry mouth (7% vs. 1%, p = 0.02), and somnolence (6% vs. 2%, p = 0.14). Conclusion Duloxetine treatment was efficacious in the improvement of anxiety and functioning in older adult patients with GAD, and the safety profile was consistent with previous GAD studies. © 2014 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd. Key points Treatment with duloxetine versus placebo can significantly reduce symptoms of generalized anxiety disorder and was associated with improved global function and increased enjoyment and satisfaction with life in patients 65 years and older. The safety and tolerability profile for duloxetine in this older adult patient population

  2. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study

    PubMed Central

    Bélanger, Stacey Ageranioti; Vanasse, Michel; Spahis, Schohraya; Sylvestre, Marie-Pierre; Lippé, Sarah; l’Heureux, François; Ghadirian, Parviz; Vanasse, Catherine-Marie; Levy, Emile

    2009-01-01

    BACKGROUND: Although several clinical trials have evaluated the impact of n-3 polyunsaturated fatty acid (PUFA) on patients with attention-deficit hyperactivity disorder (ADHD), changes in plasma PUFA composition were not always assessed following n-3 supplementation. Furthermore, no reports are available on the efficacy of n-3 PUFA in Canadian youth with ADHD. OBJECTIVES: To determine fatty acid (FA) composition, and the efficacy and safety of n-3 PUFA supplementation on ADHD clinical symptoms in French Canadian primary school children. PATIENTS AND METHODS: The Strengths and Weaknesses in ADHD and Normal Behaviors (SWAN) and Conners’ questionnaires were used to assess changes in ADHD symptoms in 37 children (only 26 children completed the study from zero to 16 weeks). They were divided into two groups (A and B), and participated in a 16-week, double-blind, one-way, crossover randomized study. In the first phase, group A received the n-3 PUFA supplement and group B received n-6 PUFA (sunflower oil) as a placebo. During the second phase, group B received the active n-3 PUFA supplement that was continued in group A. FA composition and lipid profile were assessed during the phases of the study. RESULTS: FA differences between groups were observed in the 26 patients. Supplementation with n-3 PUFA resulted in significant increases in eicosapentaenoic and docosahexaenoic acids in group A, while group B was enriched with alpha-linolenic, gamma-linolenic and homo-gamma-linolenic acids. The n-3 PUFA supplement was tolerated without any adverse effects. A statistically significant improvement in symptoms was noted based on the parent version of the Conners’ questionnaire from baseline to the end of phase 1, and this amelioration continued from phases 1 to 2, although the latter changes from phases 1 and 2 were not statistically significant in any of the subscales except for the subscale measuring inattention in group B. The improvement was greater in patients from group

  3. Metabolic syndrome does not impair the response to alfuzosin treatment in men with lower urinary tract symptoms: a double-blind, randomized, placebo-controlled study

    PubMed Central

    Altın, Selçuk; Ozan, Tunç; İlhan, Selçuk; İlhan, Nevin; Onur, Rahmi

    2015-01-01

    Objective This study is a placebo-controlled comparison of the response to alfuzosin treatment for lower urinary tract symptoms (LUTS) in patients with and without metabolic syndrome (MetS). Material and methods A total of 80 men with LUTS were included in the study. Patients had a maximum flow rate of <15 mL/sec, prostate volume of >20 mL, and International Prostate Symptom Score (IPSS) of >8. All eligible men (n=68) for evaluation were initially divided into two groups as MetS (n=34) and non-MetS (n=34) groups. Patients were further randomized to receive alfuzosin (10 mg/day) or placebo (n=17/group; a total of four groups). The outcome was measured at 12th week according to the changes from baseline in IPSS, quality of life (QoL) scores, maximum flow rate (Qmax), and postmictional residue. Results Alfuzosin significantly improved LUTS in men with and without MetS compared with patients receiving placebo (p<0.05). Mean IPSS scores in treatment groups decreased significantly, whereas patients receiving placebo had no statistically significant difference (p>0.05). Similarly, alfuzosin treatment resulted in a significant increase in Qmax in patients with LUTS/benign prostatic enlargement when compared with patients in placebo group (p<0.05). Mean QoL scores measured by IPSS-QoL and QoL questionnaires also improved significantly in patients receiving alfuzosin for 3 months regardless of the presence of MetS (p<0.05). Conclusion Our results revealed that the presence of MetS in patients with LUTS did not impair the response to alfuzosin treatment. PMID:26516595

  4. Daily Nutritional Dose Supplementation with Antioxidant Nutrients and Phytochemicals Improves DNA and LDL Stability: A Double-Blind, Randomized, and Placebo-Controlled Trial

    PubMed Central

    Kim, You Jin; Ahn, Yoon Hee; Lim, Yeni; Kim, Ji Yeon; Kim, Joohee; Kwon, Oran

    2013-01-01

    Reactive oxygen species are important risk factors for age-related diseases, but they also act as signaling factors for endogenous antioxidative defense. The hypothesis that a multi-micronutrient supplement with nutritional doses of antioxidant nutrients and phytochemicals (MP) may provide protection against oxidative damage and maintain the endogenous antioxidant defense capacity was assessed in subjects with a habitually low intake of fruits and vegetables. In a randomized, placebo-controlled, and parallel designed trial, 89 eligible subjects were assigned to either placebo or MP for eight weeks. Eighty subjects have completed the protocol and included for the analysis. MP treatment was superior at increasing serum folate (p < 0.0001) and resistance to DNA damage (p = 0.006, tail intensity; p = 0.030, tail moment by comet assay), and LDL oxidation (p = 0.009) compared with the placebo. Moreover, the endogenous oxidative defense capacity was not weakened after MP supplementation, as determined by the levels of glutathione peroxidase (p = 0.442), catalase (p = 0.686), and superoxide dismutase (p = 0.804). The serum folate level was negatively correlated with DNA damage (r = −0.376, p = 0.001 for tail density; r = −0.329, p = 0.003 for tail moment), but no correlation was found with LDL oxidation (r = −0.123, p = 0.275). These results suggest that MP use in healthy subjects with habitually low dietary fruit and vegetable intake may be beneficial in providing resistance to oxidative damage to DNA and LDL without suppressing the endogenous defense mechanisms. PMID:24352096

  5. A Capsaicin (8%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Bischoff, Joakim M.; Ringsted, Thomas K.; Petersen, Marian; Sommer, Claudia; Üçeyler, Nurcan; Werner, Mads U.

    2014-01-01

    Background Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0–10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95% CI]: 5.0 [0.09 to 9.9]; P = 0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [−0.1 to 3.9] and 0.6 [−1.2 to 2.5] fibers/mm, respectively (P = 0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated

  6. Wrinkle reduction in post-menopausal women consuming a novel oral supplement: a double-blind placebo-controlled randomized study

    PubMed Central

    Jenkins, G; Wainwright, L J; Holland, R; Barrett, K E; Casey, J

    2014-01-01

    Synopsis Objective The maintenance of youthful skin appearance is strongly desired by a large proportion of the world's population. The aim of the present study was therefore to evaluate the effect on skin wrinkling, of a combination of ingredients reported to influence key factors involved in skin ageing, namely inflammation, collagen synthesis and oxidative/UV stress. A supplemented drink was developed containing soy isoflavones, lycopene, vitamin C and vitamin E and given to post-menopausal women with a capsule containing fish oil. Method We have performed a double-blind randomized controlled human clinical study to assess whether this cocktail of dietary ingredients can significantly improve the appearance of facial wrinkles. Results We have shown that this unique combination of micronutrients can significantly reduce the depth of facial wrinkles and that this improvement is associated with increased deposition of new collagen fibres in the dermis. Conclusion This study demonstrates that consumption of a mixture of soy isoflavones, lycopene, vitamin C, vitamin E and fish oil is able to induce a clinically measureable improvement in the depth of facial wrinkles following long-term use. We have also shown, for the first time with an oral product, that the improvement is associated with increased deposition of new collagen fibres in the dermis. Résumé Objectif Le maintien de l'apparence d'une peau jeune est vivement souhaité par une grande proportion de la population mondiale. L'objectif de la présente étude était donc d'évaluer l'effet sur les rides de la peau, d'une combinaison d'ingrédients rapportés à influer sur les facteurs clés impliqués dans le vieillissement de la peau, à savoir l'inflammation, la synthèse du collagène et le stress oxydatif / UV. Une boisson supplémentée a été élaborée contenant des isoflavones de soja, le lycopène, la vitamine C et la vitamine E et donnée aux femmes ménopausées avec une capsule contenant de l

  7. A Randomized, Double-blind, Placebo-controlled, Multi-center, Extension Trial Evaluating the Efficacy of a New Oral Supplement in Women with Self-perceived Thinning Hair

    PubMed Central

    Dayan, Steven

    2015-01-01

    Objective: The purpose of this six-month, randomized, double-blind, multi-center, placebo-controlled study was to determine if the administration of a new oral supplement will promote terminal hair growth. Design: A randomized, double-blind study. Setting: Two private practices (dermatology and facial plastics). Participants: Women 21 to 75 years of age with self-perceived thinning hair. Measurements: The primary efficacy endpoint was the change in terminal and vellus hairs in a 4cm2 target area of the scalp after 90 and 180 days of treatment. Secondary endpoints were change in hair diameter and responses to Quality of Life and Self-Assessment questionnaires. Results: Subjects treated with the new oral supplement achieved a significant increase in the number of baseline terminal hairs at 90 and 180 days (for each, p<0.0001, respectively) and were significantly greater then placebo (p<0.0001). Treatment with the new oral supplement was also associated with a significant increase in baseline terminal hair diameter after 90 (p=0.006) and 180 days of treatment (p=0.001) which was significantly greater than placebo at the end of the study (p=0.003). Improvements in hair growth and hair diameter were associated with significant improvement in most responses to Self-Assessment and Quality of Life Questionnaire responses. There were no adverse events. Conclusion: The daily administration of a new oral supplement was associated with significant increases in the number of terminal and vellus hairs and hair diameter. Most study participants believed the use of the oral supplement resulted in significant improvement in skin and hair quality and quality of life. PMID:26705444

  8. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan

    PubMed Central

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75–225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery–Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (−10.76; P=0.031), but not in the flexible-dose (−10.37; P=0.106) group compared with placebo (−9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan. PMID:26513202

  9. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release and a long-term extension study for patients with major depressive disorder in Japan.

    PubMed

    Higuchi, Teruhiko; Kamijima, Kunitoshi; Nakagome, Kazuyuki; Itamura, Rio; Asami, Yuko; Kuribayashi, Kazuhiko; Imaeda, Takayuki

    2016-01-01

    The aim of this study was to assess antidepressant efficacy and safety of venlafaxine extended release in Japanese patients with major depressive disorder (MDD). We carried out a double-blinded, placebo-controlled, randomized study using fixed (75 mg/day) and flexible (75-225 mg/day, most patients attained to 225 mg/day) doses, followed by the long-term, open-labeled, extension study. Outpatients aged at least 20 years diagnosed with MDD were included. The primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression (HAM-D17) score at week 8; secondary efficacy measures included the Montgomery-Åsberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology self-report version, HAM-D6, and Clinical Global Impression scales in the double-blinded study. Overall, 538 patients were randomized; significant differences were observed in the primary efficacy variable in the fixed-dose group (-10.76; P=0.031), but not in the flexible-dose (-10.37; P=0.106) group compared with placebo (-9.25). However, the flexible-dose group showed significant efficacy in several secondary measures. Treatment-related adverse events in the treatment period were 51.7 and 67.8% in the fixed-dose and flexible-dose groups, respectively, versus 38.8% with placebo. Throughout the study period, no Japanese-specific adverse events were observed. Thus, venlafaxine extended release was efficacious and safe for MDD treatment in Japan.

  10. Double-blind placebo-controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

    PubMed Central

    Ling, Walter; Shoptaw, Steven; Hillhouse, Maureen; Bholat, Michelle A.; Charuvastra, Charles; Heinzerling, Keith; Chim, David; Annon, Jeffrey; Dowling, Patrick T.; Doraimani, Geetha

    2014-01-01

    Aims To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence. Design A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Setting Three substance abuse treatment clinics: two in-patient, one out-patient. Participants Treatment-seeking, methamphetamine-dependent adults (n = 120). Measurements Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. Findings No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. Conclusions The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving. PMID:22082089

  11. Metabolic management in overweight subjects with naive impaired fasting glycaemia by means of a highly standardized extract from Cynara scolymus: a double-blind, placebo-controlled, randomized clinical trial.

    PubMed

    Rondanelli, Mariangela; Opizzi, Annalisa; Faliva, Milena; Sala, Patrizio; Perna, Simone; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Giacosa, Attilio

    2014-01-01

    The aim of this study is to evaluate the efficacy of a dietary supplementation with an extract from Cynara scolymus (Cs) on the glucose pattern in a group of patients with naïve impaired fasting glycaemia (IFG). A randomized, double-blind, placebo-controlled trial has been performed in 55 overweight subjects with IFG (fasting blood glucose [FBG]: 6.11 ± 0.56 mmol/l). These subjects were randomly assigned to supplement their diet with either an extract from Cs (600 mg/d) (26 subjects) or placebo (29 matched subjects) for 8 weeks. The decrease of FBG was the primary endpoint. The assessment of Homeostatic Metabolic Assessment (HOMA), glycosylated haemoglobin, A1c-Derived Average Glucose (ADAG), lipidic pattern and anthropometric parameters were the secondary endpoints. The within groups and percent changes from baseline were analyzed by the signed rank test. The comparison between groups was performed by Wilcoxon's two sample test. The supplemented group had significant decreases of: FBG (-9.6%), HOMA (-11.7%), glycosylated haemoglobin (-2.3%), ADAG (-3.1%) and lipidic pattern. The placebo group did not show any significant difference. Compared with the placebo, the supplemented group showed a significant difference in FBG, HOMA and lipidic pattern. These data demonstrate the efficacy of Cs extract on the reduction of glycometabolic parameters in overweight subjects with IFG. PMID:23440660

  12. The effect of Polygonum minus extract on cognitive and psychosocial parameters according to mood status among middle-aged women: a randomized, double-blind, placebo-controlled study

    PubMed Central

    Shahar, Suzana; Aziz, Ainor Farahin; Ismail, Siti Nur Arina; Yahya, Hanis Mastura; Din, Normah Che; Manaf, Zahara Abdul; Badrasawi, Manal M

    2015-01-01

    Background Polygonum minus (PM) or locally known in Malaysia, as “kesum” is rich in micronutrients and natural antioxidants. However, its beneficial effect on outcome associates with oxidative stress including cognitive function is yet to be discovered. We assessed the efficacy of PM extract (LineMinus™) on cognitive function and psychosocial status among middle-aged women in Klang Valley of Malaysia. Methods A randomized, double-blind, placebo-controlled trial among 35 healthy middle-aged women was performed, and subjects were randomized to receive either 250 mg PM or placebo of 100 mg maltodextrin each were taken twice daily for 6 weeks. Subjects were assessed for neuropsychological test, psychosocial status, and anthropometric at baseline, week 3, and week 6. Biomarkers were also determined at baseline and week 6. Results The supplementation of PM showed significant intervention effect on Digit Span test (P<0.05) social functioning domain of 36-Item Short Form Health Survey (P<0.05) among subjects with mood disturbance. While, among subjects with good mood, PM supplementation improved Wechsler Abbreviated Scale of Intelligence (WASI) for IQ verbal (P=0.016) and Full Scale IQ of WASI (P=0.004). There were no adverse effects reported for the supplementation as indicated using biomarkers, including liver function and clinical symptoms. Conclusion Supplementation of PM is safe to be consumed for 6 weeks, with potential benefits to attention, short-term memory, improved quality of life, and mood, as well as IQ. PMID:26445532

  13. Metabolic management in overweight subjects with naive impaired fasting glycaemia by means of a highly standardized extract from Cynara scolymus: a double-blind, placebo-controlled, randomized clinical trial.

    PubMed

    Rondanelli, Mariangela; Opizzi, Annalisa; Faliva, Milena; Sala, Patrizio; Perna, Simone; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Giacosa, Attilio

    2014-01-01

    The aim of this study is to evaluate the efficacy of a dietary supplementation with an extract from Cynara scolymus (Cs) on the glucose pattern in a group of patients with naïve impaired fasting glycaemia (IFG). A randomized, double-blind, placebo-controlled trial has been performed in 55 overweight subjects with IFG (fasting blood glucose [FBG]: 6.11 ± 0.56 mmol/l). These subjects were randomly assigned to supplement their diet with either an extract from Cs (600 mg/d) (26 subjects) or placebo (29 matched subjects) for 8 weeks. The decrease of FBG was the primary endpoint. The assessment of Homeostatic Metabolic Assessment (HOMA), glycosylated haemoglobin, A1c-Derived Average Glucose (ADAG), lipidic pattern and anthropometric parameters were the secondary endpoints. The within groups and percent changes from baseline were analyzed by the signed rank test. The comparison between groups was performed by Wilcoxon's two sample test. The supplemented group had significant decreases of: FBG (-9.6%), HOMA (-11.7%), glycosylated haemoglobin (-2.3%), ADAG (-3.1%) and lipidic pattern. The placebo group did not show any significant difference. Compared with the placebo, the supplemented group showed a significant difference in FBG, HOMA and lipidic pattern. These data demonstrate the efficacy of Cs extract on the reduction of glycometabolic parameters in overweight subjects with IFG.

  14. The effects of lisdexamfetamine dimesylate on the driving performance of young adults with ADHD: a randomized, double-blind, placebo-controlled study using a validated driving simulator paradigm.

    PubMed

    Biederman, Joseph; Fried, Ronna; Hammerness, Paul; Surman, Craig; Mehler, Bruce; Petty, Carter R; Faraone, Stephen V; Miller, Carolyn; Bourgeois, Michelle; Meller, Benjamin; Godfrey, Kathryn M; Reimer, Bryan

    2012-04-01

    Young adults with Attention Deficit Hyperactivity Disorder (ADHD) have been shown to be at increased risk for impairment in driving behaviors. While stimulant medications have proven efficacy in reducing ADHD symptomatology, there is limited knowledge as to their effects on driving impairment. The main aim of this study was to assess the impact of lisdexamfetamine dimesylate (LDX) on driving performance in young adults with ADHD using a validated driving simulation paradigm. This was a randomized, double-blind, 6-week, placebo-controlled, parallel-design study of LDX vs. a placebo on driving performance in a validated driving simulation paradigm. Subjects were sixty-one outpatients of both sexes, 18-26 years of age, who met DSM-IV criteria for ADHD. Subjects were randomized to receive LDX or placebo after a baseline driving simulation and completed a second driving simulation six weeks after beginning drug or placebo. Examination of reaction time across five surprise events at post-treatment showed a significant positive effect of medication status. LDX treatment was also associated with significantly fewer accidents vs. placebo. LDX treatment was associated with significantly faster reaction times and a lower rate of simulated driving collisions than placebo. These results suggest that LDX may reduce driving risks in young adults with ADHD. PMID:22277301

  15. Effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly: secondary analysis of a randomized, double-blind, placebo-controlled trial.

    PubMed

    van de Rest, Ondine; van der Zwaluw, Nikita L; Tieland, Michael; Adam, Jos J; Hiddink, Gert Jan; van Loon, Luc J C; de Groot, Lisette C P G M

    2014-01-01

    Physical activity has been proposed as one of the most effective strategies to prevent cognitive decline. Protein supplementation may exert an additive effect. The effect of resistance-type exercise training with or without protein supplementation on cognitive functioning in frail and pre-frail elderly people was assessed in a secondary analysis. Two 24-week, double-blind, randomized, placebo-controlled intervention studies were carried out in parallel. Subjects performed a resistance-type exercise program of two sessions per week (n=62) or no exercise program (n=65). In both studies, subjects were randomly allocated to either a protein (2×15 g daily) or a placebo drink. Cognitive functioning was assessed with a neuropsychological test battery focusing on the cognitive domains episodic memory, attention and working memory, information processing speed, and executive functioning. In frail and pre-frail elderly, resistance-type exercise training in combination with protein supplementation improved information processing speed (changes in domain score 0.08±0.51 versus -0.23±0.19 in the non-exercise group, p=0.04). Exercise training without protein supplementation was beneficial for attention and working memory (changes in domain scores 0.35±0.70 versus -0.12±0.69 in the non-exercise group, p=0.02). There were no significant differences among the intervention groups on the other cognitive tests or domain scores.

  16. Intravenous dexamethasone versus ketamine gargle versus intravenous dexamethasone combined with ketamine gargle for evaluation of post-operative sore throat and hoarseness: A randomized, placebo-controlled, double blind clinical trial

    PubMed Central

    Safavi, Mohammadreza; Honarmand, Azim; Fariborzifar, Arghavan; Attari, Mohammadali

    2014-01-01

    Background: Sore throat and hoarseness are the most frequent subjective complaints after tracheal intubation for general anesthesia. We conducted a prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intravenous (IV) dexamethasone plus ketamine gargle for reducing the incidence and severity of post-operative sore throat (POST) and hoarseness. Materials and Methods: 140 patients (aged 16-65 year) scheduled for elective surgery were enrolled. Patients were randomly allocated into four groups of 35 subjects each: Group K, gargled 40 mg ketamine in 30 ml saline; Group D, were infused 0.2 mg/kg IV dexamethasone; Group KD, gargled 40 mg ketamine in 30 ml saline plus 0.2 mg/kg IV dexamethasone; Group P (placebo) that received saline (gargle and IV). POST was graded at 0, 2, 4, 8, 16 and 24 h after operation on a four-point scale (0-3). Results: The incidence and severity of POST were significantly lower in Group KD, compared with the other groups at all times after tracheal extubation for up to 24 h (P < 0.05). Also the incidence and severity of hoarseness were significantly lower in each Groups of KD and K and D compared with group placebo (P < 0.05). Conclusion: The prophylactic use of 0.2 mg/kg of IV dexamethasone plus ketamine gargle significantly reduced the incidence and severity of POST compared with using each of these drugs alone or using placebo. PMID:25371869

  17. Immunomodulation in Middle-Aged Humans Via the Ingestion of Physta® Standardized Root Water Extract of Eurycoma longifolia Jack--A Randomized, Double-Blind, Placebo-Controlled, Parallel Study.

    PubMed

    George, Annie; Suzuki, Naoko; Abas, Azreena Binti; Mohri, Kiminori; Utsuyama, Masanori; Hirokawa, Katsuiku; Takara, Tsuyoshi

    2016-04-01

    This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta® to modulate human immunity in a middle-aged Japanese population. This randomized, double-blind, placebo-controlled, parallel study was conducted for 4 weeks. Eighty-four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty-three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p < 0.05). The numbers of total, naïve, and CD4(+) T cells were also higher in the TA group than those in P group (p < 0.05). No severe adverse events were observed. The results suggest that ingestion of the root water extract of TA (Physta®) enhances comprehensive immunity in both middle-aged men and women. This study is registered in UMIN-CTR (UMIN000011753).

  18. Famciclovir suppression of asymptomatic and symptomatic recurrent anogenital herpes simplex virus shedding in women: a randomized, double-blind, double-dummy, placebo-controlled, parallel-group, single-center trial.

    PubMed

    Sacks, Stephen L

    2004-04-15

    Genital herpes is most often transmitted while the patient is asymptomatic, presumably during episodes of viral shedding. To determine whether famciclovir is effective in reducing asymptomatic shedding, women with frequent, recurrent genital outbreaks were enrolled in a randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 112-day trial of suppressive treatment with famciclovir for anogenital viral shedding. Sixty women received 125 mg of famciclovir 3 times daily, 59 received 250 mg of famciclovir 3 times daily, and 58 received placebo. Patients recorded symptoms and self-obtained cultures daily. Famciclovir reduced asymptomatic shedding, compared with placebo (P < .0001). The onset of asymptomatic shedding was also delayed (P < .0001). Famciclovir reduced symptomatic shedding in a dose-dependent manner (0.72% for 125 mg 3 times daily vs. 0.19% for 250 mg 3 times daily [P < .0001] vs. 5.53% for placebo [P < .0001]). In conclusion, suppressive treatment with famciclovir reduced both asymptomatic and symptomatic viral shedding and delayed the onset of asymptomatic shedding in women with frequently recurring genital herpes. Studies to examine the effects of suppression by famciclovir on the transmission of genital herpes are warranted.

  19. Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

    PubMed

    Amaryan, G; Astvatsatryan, V; Gabrielyan, E; Panossian, A; Panosyan, V; Wikman, G

    2003-05-01

    Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special extracts standardized for the content of Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in FMF patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with FMF. PMID:12809357

  20. Lorcaserin Administration Decreases Activation of Brain Centers in Response to Food Cues and These Emotion- and Salience-Related Changes Correlate With Weight Loss Effects: A 4-Week-Long Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

    PubMed

    Farr, Olivia M; Upadhyay, Jagriti; Gavrieli, Anna; Camp, Michelle; Spyrou, Nikolaos; Kaye, Harper; Mathew, Hannah; Vamvini, Maria; Koniaris, Anastasia; Kilim, Holly; Srnka, Alexandra; Migdal, Alexandra; Mantzoros, Christos S

    2016-10-01

    Lorcaserin is a serotonin 5-hydroxytryptamine 2c receptor agonist effective in treating obesity. Studies in rodents have shown that lorcaserin acts in the brain to exert its weight-reducing effects, but this has not yet been studied in humans. We performed a randomized, placebo-controlled, double-blind trial with 48 obese participants and used functional MRI to study the effects of lorcaserin on the brain. Subjects taking lorcaserin had decreased brain activations in the attention-related parietal and visual cortices in response to highly palatable food cues at 1 week in the fasting state and in the parietal cortex in response to any food cues at 4 weeks in the fed state. Decreases in emotion- and salience-related limbic activity, including the insula and amygdala, were attenuated at 4 weeks. Decreases in caloric intake, weight, and BMI correlated with activations in the amygdala, parietal, and visual cortices at baseline. These data suggest that lorcaserin exerts its weight-reducing effects by decreasing attention-related brain activations to food cues (parietal and visual cortices) and emotional and limbic activity (insula, amygdala). Results indicating that baseline activation of the amygdala relates to increased efficacy suggest that lorcaserin would be of particular benefit to emotional eaters.

  1. The efficacy of the dopamine D2/D3 antagonist tiapride in maintaining abstinence: a randomized, double-blind, placebo-controlled trial in 299 alcohol-dependent patients.

    PubMed

    Bender, Stefan; Scherbaum, Norbert; Soyka, Michael; Rüther, Eckart; Mann, Karl; Gastpar, Markus

    2007-10-01

    In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor antagonist tiapride is effective in maintaining abstinence after detoxification in alcohol-dependent patients. The rationale of the study was based on the relevance of the dopaminergic system for addictive behaviour as well as some preliminary studies. A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study was conducted. A total of 299 detoxified alcohol-dependent patients (ICD-10: F10.2) received either tiapride (300 mg/d) or placebo over a 24-wk study period. Subjects with severe comorbid psychiatric disorder such as schizophrenia or Wernicke-Korsakoff syndrome were excluded. Primary outcome variable was the time to first relapse with relapse defined as any alcohol consumption after detoxification. Data analysis was done with Kaplan-Meier estimates with log-rank test (one-sided, p<0.05). Tiapride was not superior to placebo in maintaining abstinence. The time to first relapse was 71 d in the tiapride group and 92 d in the placebo group (log-rank test, p=0.9895). Relapse rate was higher in the intervention group (54.4%) than in the control group (40.7%). Like the dopamine antagonist flupenthixol, tiapride was not effective in maintaining alcohol abstinence. Regarding the high success rate in the placebo group the influence of psychosocial treatment in studies investigating drug effects on the course of alcohol dependence has to be considered.

  2. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner

    PubMed Central

    Ferraresi, Cleber; Beltrame, Thomas; Fabrizzi, Fernando; do Nascimento, Eduardo Sanches Pereira; Karsten, Marlus; de Oliveira Francisco, Cristina; Borghi-Silva, Audrey; Catai, Aparecida Maria; Cardoso, Daniel Rodrigues; Ferreira, Antonio Gilberto; Hamblin, Michael R.; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-01-01

    Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase – CK and alanine) and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy (1H NMR). A LED cluster with 50 LEDs (λ = 850 nm; 50mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (~−9 s), decreased O2 deficit (~−10 L), increased the VO2 from the slow component phase (~+348 ml min−1) and increased the time limit of exercise (~+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance. PMID:25585514

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

    PubMed

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

    2013-08-01

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

  4. Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study.

    PubMed

    Koll, R; Buhr, M; Dieter, R; Pabst, H; Predel, H G; Petrowicz, O; Giannetti, B; Klingenburg, S; Staiger, C

    2004-09-01

    Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory, analgesic and tissue regenerating properties. In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Compared to placebo, the active treatment was clearly superior regarding the reduction of pain (tonometric measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure-of-eight method, p = 0.0001). Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method), and global efficacy. Under active treatment, no adverse drug reactions were reported. The good local and global tolerance of the trial medication could also be confirmed. The study results are consistent with the known pre-clinical and clinical data concerning comfrey. PMID:15500257

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

    PubMed Central

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

    2014-01-01

    Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40–65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers. PMID:24550993

  6. In vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidant-rich fruit and berry juice blend. Results of a pilot and randomized, double-blinded, placebo-controlled, crossover study.

    PubMed

    Jensen, Gitte S; Wu, Xianli; Patterson, Kelly M; Barnes, Janelle; Carter, Steve G; Scherwitz, Larry; Beaman, Robert; Endres, John R; Schauss, Alexander G

    2008-09-24

    This study investigated the in vitro and in vivo antioxidant and anti-inflammatory properties of a juice blend (JB), MonaVie Active, containing a mixture of fruits and berries with known antioxidant activity, including acai, a palm fruit, as the predominant ingredient. The phytochemical antioxidants in the JB are primarily in the form of anthocyanins, predominantly cyanidin 3-rutoside, cyanidin 3-diglycoside, and cyanidin 3-glucoside. The cell-based antioxidant protection of erythrocytes (CAP-e) assay demonstrated that antioxidants in the JB penetrated and protected cells from oxidative damage ( p < 0.001), whereas polymorphonuclear cells showed reduced formation of reactive oxygen species ( p < 0.003) and reduced migration toward three different pro-inflammatory chemoattractants: fmlp ( p < 0.001), leukotriene B4 ( p < 0.05), and IL-8 ( p < 0.03). A randomized, double-blinded, placebo-controlled, crossover trial with 12 healthy subjects examined the JB's antioxidant activity in vivo. Blood samples at baseline, 1 h, and 2 h following consumption of the JB or placebo were tested for antioxidant capacity using several antioxidant assays and the TBARS assay, a measure of lipid peroxidation. A within subject comparison showed an increase in serum antioxidants at 1 h ( p < 0.03) and 2 h ( p < 0.015), as well as inhibition of lipid peroxidation at 2 h ( p < 0.01) postconsumption.

  7. A 3-month, randomized, double-blind, placebo-controlled study evaluating the ability of an extra-strength marine protein supplement to promote hair growth and decrease shedding in women with self-perceived thinning hair.

    PubMed

    Ablon, Glynis

    2015-01-01

    An oral marine protein supplement (MPS) is designed to promote hair growth in women with temporary thinning hair (Viviscal Extra Strength; Lifes2good, Inc., Chicago, IL). This double-blind, placebo-controlled study assessed the ability of MPS to promote terminal hair growth in adult women with self-perceived thinning hair associated with poor diet, stress, hormonal influences, or abnormal menstrual cycles. Adult women with thinning hair were randomized to receive MPS (N = 30) or placebo (N = 30) twice daily for 90 days. Digital images were obtained from a 4 cm(2) area scalp target area. Each subject's hair was washed and shed hairs were collected and counted. After 90 days, these measures were repeated and subjects completed Quality of Life and Self-Assessment Questionnaires. MPS-treated subjects achieved a significant increase in the number of terminal hairs within the target area (P < 0.0001) which was significantly greater than placebo (P < 0.0001). MPS use also resulted in significantly less hair shedding (P = 0.002) and higher total Self-Assessment (P = 0.006) and Quality of Life Questionnaires scores (P = 0.035). There were no reported adverse events. MPS promotes hair growth and decreases hair loss in women suffering from temporary thinning hair. This trial is registered with ClinicalTrials.gov Identifier: NCT02297360.

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

    PubMed

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

    2014-01-01

    Background. Physta is a proprietary product containing a freeze-dried water extract of Eurycoma longifolia (tongkat ali), which is traditionally used as an energy enhancer and aphrodisiac. We aim to evaluate a 300 mg combination of Physta and Polygonum minus, an antioxidant, with regard to sexual performance and well-being in men. Methods. Men that aged 40-65 years were screened for this 12-week randomized, double-blind, placebo-controlled, parallel-group study. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Three adverse events were reported in the active group and four in the placebo group, none of which were attributed to study product. Laboratory evaluations, including liver and kidney function testing, showed no clinically significant abnormality. Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers. PMID:24550993

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

    PubMed

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

    2013-08-01

    Energy drinks are widely available mostly containing glucose, and several have been demonstrated to improve alertness and cognitive function; these effects generally being identified 30-60min after administration. The present study assessed whether an energy shot without carbohydrates would affect major aspects of cognitive function and also mood in volunteers over a 6h time period. This randomized, double-blind, placebo-controlled,crossover study compared the acute effects of the energy shot with a matching placebo in 94 healthy volunteers. Cognitive function was assessed with a widely used set of automated tests of attention and memory. Mood was assessed with the Bond-Lader, Beck Anxiety Index, Beck Depression Index, Chalder Fatigue Scales (CFS), and the POMS. The volunteers were requested to limit their sleep to between 3 and 6h the night before each testing day. Compared to the placebo, the energy shot significantly improved 6 validated composite cognitive function measures from the CDR System as well as self-rated alertness; the benefits on 4 of the cognitive measures still remaining at 6h. The overall effect sizes of the performance improvements were in the small to medium range and thus notable in this field. In conclusion, an energy shot can significantly improve important aspects of cognitive function for up to 6h compared to placebo in partially sleep-deprived healthy volunteers. PMID:23587521

  10. A 3-Month, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Ability of an Extra-Strength Marine Protein Supplement to Promote Hair Growth and Decrease Shedding in Women with Self-Perceived Thinning Hair

    PubMed Central

    Ablon, Glynis

    2015-01-01

    An oral marine protein supplement (MPS) is designed to promote hair growth in women with temporary thinning hair (Viviscal Extra Strength; Lifes2good, Inc., Chicago, IL). This double-blind, placebo-controlled study assessed the ability of MPS to promote terminal hair growth in adult women with self-perceived thinning hair associated with poor diet, stress, hormonal influences, or abnormal menstrual cycles. Adult women with thinning hair were randomized to receive MPS (N = 30) or placebo (N = 30) twice daily for 90 days. Digital images were obtained from a 4 cm2 area scalp target area. Each subject's hair was washed and shed hairs were collected and counted. After 90 days, these measures were repeated and subjects completed Quality of Life and Self-Assessment Questionnaires. MPS-treated subjects achieved a significant increase in the number of terminal hairs within the target area (P < 0.0001) which was significantly greater than placebo (P < 0.0001). MPS use also resulted in significantly less hair shedding (P = 0.002) and higher total Self-Assessment (P = 0.006) and Quality of Life Questionnaires scores (P = 0.035). There were no reported adverse events. MPS promotes hair growth and decreases hair loss in women suffering from temporary thinning hair. This trial is registered with ClinicalTrials.gov Identifier: NCT02297360. PMID:25883641

  11. Comparative effects of propranolol and verapamil alone and in combination on left ventricular function and volumes in patients with chronic exertional angina: a double-blind, placebo-controlled, randomized, crossover study with radionuclide ventriculography

    SciTech Connect

    Johnston, D.L.; Gebhardt, V.A.; Donald, A.; Kostuk, W.J.

    1983-12-01

    With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebo-controlled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (118 +/- 28 mm Hg/min) was significantly greater than that by propranolol (135 +/- 27 mm Hg/min) or verapamil alone (163 +/- 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise glo