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Sample records for placebo-controlled study raise

  1. Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study.

    PubMed

    Kongsakon, Ronnachai; Papadopoulos, Konstantinos I; Saguansiritham, Rapeepun

    2005-09-01

    The present study aimed to assess the safety and efficacy of mirtazapine in amphetamine detoxification in a 14-day randomized, placebo-controlled pilot trial in a Thai population. Subjects retained at a Specialized Probation Center, Department of Probation, Ministry of Justice, Thailand (n=20), who met DSM-IV criteria for amphetamine dependence and the inclusion criteria of the study, were randomized for either mirtazapine treatment or placebo. Efficacy was assessed by the Amphetamine Withdrawal Questionnaire (AWQ) for amphetamine withdrawal symptoms and the Montgomery-Asberg Depression rating scale (MADRS) for depression. Mirtazapine safety was assessed by interview during each follow-up period on days 3 and 14 after treatment. Nine subjects were randomized to the mirtazapine group and 11 to the placebo group. Among the initial 20 subjects, 16 (seven in the mirtazapine and nine in the placebo group) completed the study. There were significant improvements in the total AWQ score changes in the mirtazapine group versus placebo both at days 3 (P<0.005) and 14 (P<0.030). Significant improvements in favour of mirtazapine were also seen in the hyperarousal and the anxiety subscale score changes at days 3 (P<0.029) and 14 (P<0.018), respectively. No significant differences were seen (P>0.05) in the MADRS scores changes within or between the groups. Mild adverse events, such as headache, sedation, nausea and vomiting, were reported. In conclusion, despite its small sample size, this randomized, placebo-controlled pilot trial lends support to the hypothesis that mirtazapine may be an option in the meager armamentarium of amphetamine detoxification treatment. PMID:16096515

  2. Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study

    ERIC Educational Resources Information Center

    Kafantaris, Vivian; Coletti, Daniel J.; Dicker, Robert; Padula, Gina; Pleak, Richard R.; Alvir, Jose Ma. J.; Kane, John M.

    2004-01-01

    Objective: There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents. Method: In this discontinuation study, participants received open treatment with lithium at…

  3. Placebo-controlled study in neuromyelitis optica—Ethical and design considerations

    PubMed Central

    Cree, Bruce AC; Bennett, Jeffrey L; Sheehan, Mark; Cohen, Jeffrey; Hartung, Hans-Peter; Aktas, Orhan; Kim, Ho Jin; Paul, Friedemann; Pittock, Sean; Weinshenker, Brian; Wingerchuk, Dean; Fujihara, Kazuo; Cutter, Gary; Patra, Kaushik; Flor, Armando; Barron, Gerard; Madani, Soraya; Ratchford, John N; Katz, Eliezer

    2015-01-01

    Background: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. Objective: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical–scientific integrity. Methods: We assessed the “standard of care” for NMO to establish the ethical framework for a placebo-controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. Results: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. Conclusion: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path. PMID:26666258

  4. Multicentre Double-Blind Placebo-Controlled Food Challenge Study in Children Sensitised to Cashew Nut

    PubMed Central

    van der Valk, Johanna P. M.; Gerth van Wijk, Roy; Dubois, Anthony E. J.; de Groot, Hans; Reitsma, Marit; Vlieg-Boerstra, Berber; Savelkoul, Huub F. J.; Wichers, Harry J.; de Jong, Nicolette W.

    2016-01-01

    Background Few studies with a limited number of patients have provided indications that cashew-allergic patients may experience severe allergic reactions to minimal amounts of cashew nut. The objectives of this multicentre study were to assess the clinical relevance of cashew nut sensitisation, to study the clinical reaction patterns in double-blind placebo-controlled food challenge tests and to establish the amount of cashew nuts that can elicit an allergic reaction. Methods and Findings A total of 179 children were included (median age 9.0 years; range 2–17 years) with cashew nut sensitisation and a clinical history of reactions to cashew nuts or unknown exposure. Sensitised children who could tolerate cashew nuts were excluded. The study included three clinical visits and a telephone consultation. During the first visit, the medical history was evaluated, physical examinations were conducted, blood samples were drawn and skin prick tests were performed. The children underwent a double-blind placebo-controlled food challenge test with cashew nut during the second and third visits. The study showed that 137 (76.5%) of the sensitised children suspected of allergy to cashew nut had a positive double-blind placebo-controlled food challenge test, with 46% (63) manifesting subjective symptoms to the lowest dose of 1 mg cashew nut protein and 11% (15) developing objective symptoms to the lowest dose. Children most frequently had gastro-intestinal symptoms, followed by oral allergy and skin symptoms. A total of 36% (49/137) of the children experienced an anaphylactic reaction and 6% (8/137) of the children were treated with epinephrine. Conclusion This prospective study demonstrated a strikingly high percentage of clinical reactions to cashew nut in this third line population. Severe allergic reactions, including anaphylaxis requiring epinephrine, were observed. These reactions were to minimal amounts of cashew nut, demonstrated the high potency of this allergens

  5. Adjunctive Memantine Therapy for Cognitive Impairment in Chronic Schizophrenia: A Placebo-Controlled Pilot Study

    PubMed Central

    Lee, Jung Goo; Lee, Sae Woom; Lee, Bong Ju; Park, Sung Woo; Kim, Gyung Mee

    2012-01-01

    Objective To investigate the effects of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on cognitive impairments in patients with chronic schizophrenia. Methods A 12-week, placebo-controlled trial was conducted to determine the effectiveness of memantine as an adjunctive treatment with conventional antipsychotic medications in 26 patients with chronic schizophrenia. The subjects were evaluated with the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), and a standard neuropsychological screening test. Results Memantine treatment was not associated with significantly improved cognitive test scores compared with the placebo control treatment. An improvement in the scores on the PANSS negative subscale was noted with memantine, but it was not significant. Conclusion Adjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study. Memantine, however, was tolerated well and did not exacerbate positive symptoms in patients with chronic schizophrenia. PMID:22707968

  6. Acute effects of waterpipe tobacco smoking: a double-blind, placebo-control study

    PubMed Central

    Blank, Melissa D.; Cobb, Caroline O.; Kilgalen, Barbara; Austin, Janet; Weaver, Michael F.; Shihadeh, Alan; Eissenberg, Thomas

    2011-01-01

    Background Waterpipe tobacco smoking usually involves heating flavored tobacco with charcoal and inhaling the resulting smoke after it has passed through water. Waterpipe tobacco smoking increases heart rate and produces subjective effects similar to those reported by cigarette smokers. These responses are thought to be nicotine-mediated, though no placebo-control studies exist. Accordingly, this double-blind, placebo-control study compared the acute physiological and subjective effects of waterpipe tobacco smoking to those produced when participants used a waterpipe to smoke a flavor-matched, tobacco-free preparation. Methods Occasional waterpipe tobacco smokers (N=37; 2–5 monthly smoking episodes for ≥ 6 months) completed two double-blind, counterbalanced sessions that differed by product: preferred brand/flavor of waterpipe tobacco or flavor-matched, tobacco-free preparation. For each 45-minute, ad lib smoking episode blood and expired air CO were sampled, cardiovascular and respiratory response were measured, and subjective response was assessed. Results Waterpipe tobacco smoking significantly increased mean (±SEM) plasma nicotine concentration (3.6±0.7 ng/ml) and heart rate (8.6±1.4 bpm) while placebo did not (0.1±0.0 ng/ml; 1.3±0.9 bpm). For carboxyhemoglobin (COHb) and expired air CO, significant increases were observed for tobacco (3.8±0.4%; 27.9±2.6 ppm) and for placebo (3.9±0.4%; 27.7±3.3 ppm) with no differences across condition. Independent of condition, symptoms of nicotine/tobacco abstinence (e.g., “urges to smoke”, “anxious”) were reduced and direct effects (e.g., “dizzy”, “satisfy”) increased. Discussion These results from the first placebo-control study of waterpipe tobacco smoking demonstrate that waterpipe-induced heart rate increases are almost certainly mediated by nicotine though the subjective effects observed in these occasional smokers were not. PMID:21277706

  7. 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…

  8. 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…

  9. Baclofen reduces binge eating in a double-blind, placebo-controlled, crossover study.

    PubMed

    Corwin, Rebecca L; Boan, Jarol; Peters, Kathryn F; Ulbrecht, Jan S

    2012-09-01

    Baclofen has shown promise in treating substance use disorders and also reduced binge frequency in an open-label trial. This placebo-controlled, double-blind, crossover study further assessed the effects of baclofen on binge eating. Twelve individuals who self-reported binge eating completed the study. Data were collected during a run-in period (no drug or placebo), placebo phase (48 days), and baclofen phase (titrated up to 60 mg daily or the maximum tolerated dose, 48 days). All the participants were exposed to all conditions. Participants completed a binge diary daily, and the Binge Eating Scale (BES), Food Craving Inventory-II (FCI-II), and Hospital Anxiety and Depression Scale (HADS) at regular intervals throughout the study. Baclofen significantly reduced binge frequency relative to placebo and run-in (P<0.05). This confirms results from the previous open-label trial. Baclofen also produced slight, but significant, increases in depression symptomatology as assessed by the HADS. Binge severity (BES scores) and craving (FCI-II scores) were significantly reduced during placebo and baclofen phases, that is both measures exhibited significant placebo effects. Tiredness, fatigue, and upset stomach were the most commonly reported side-effects. These results indicate that baclofen may be a useful treatment for binge eating in some patients. PMID:22854310

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

    PubMed Central

    Sadeghian, Homa; Motiei-Langroudi, Rouzbeh

    2015-01-01

    Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive) and preventive (prophylactic) treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants), and anti-epileptic drugs (valproate, gabapentin, etc). Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27), valproate 500 mg/d (n = 32) or placebo (n = 26). The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate. PMID:25745310

  11. Proton pump inhibition prevents gastrointestinal bleeding in ultramarathon runners: a randomised, double blinded, placebo controlled study

    PubMed Central

    Thalmann, M; Sodeck, G H; Kavouras, S; Matalas, A; Skenderi, K; Yannikouris, N; Domanovits, H

    2006-01-01

    Background Ultra‐endurance running is emerging as a popular sport in Western industrialised countries. Gastrointestinal bleeding has been reported to be an adverse effect in these runners. Objective To see if the oral administration of a proton pump inhibitor would reduce the incidence of gastrointestinal bleeding in an ultramarathon. Methods In a randomised, double blinded, placebo controlled study, a prophylactic regimen of three days of an oral proton pump inhibitor (pantoprazole 20 mg) was tested in healthy athletes participating in the Spartathlon ultramarathon. The incidence of gastrointestinal bleeding was assessed by a stool guaiac test. Results Results were obtained for 70 healthy volunteers. The data for 20 of 35 runners in the intervention group and 17 of 35 runners in the placebo group were entered into the final analysis. At the end of the ultramarathon, two subjects in the intervention group and 12 in the placebo group had positive stool guaiac tests (risk difference 0.86; 95% confidence interval 0.45 to 0.96; p  =  0.001). Conclusion A short prophylactic regimen of oral proton pump inhibition can successfully decrease the incidence of gastrointestinal bleeding in participants in an ultramarathon. PMID:16556794

  12. 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…

  13. Fluoxetine and premature ejaculation: a double-blind, crossover, placebo-controlled study.

    PubMed

    Haensel, S M; Klem, T M; Hop, W C; Slob, A K

    1998-02-01

    The purpose of this study was to investigate the effect of fluoxetine on sexual function in men with premature ejaculation and/or erectile dysfunction and control subjects in a prospective, double-blind, placebo-controlled, crossover study. There were four groups: (1) premature ejaculation (PE, N = 9); (2) premature ejaculation and erectile dysfunction (PE/ED, N = 9); (3) erectile dysfunction (ED, N = 7); and (4) healthy, sexually functional control subjects (N = 15). The study consisted of three 4-week periods: fluoxetine, washout, and placebo (or vice versa). Fluoxetine began at 5 mg/day for 2 weeks, followed by 10 mg/day for 2 weeks. At weeks 0, 4, 8, and 12, subjects visited the laboratory for evaluation of sexual function and assessment of erectile response, ejaculation, and sexual arousal to visual erotic stimulation without and with concomitant vibrotactile stimulation to the penis. At home, daily logs for sexual activities and feelings of well-being were maintained, and nocturnal penile tumescence was measured. The latency to ejaculation increased significantly in the PE/ED group (p = 0.03) and in the PE and the PE/ED group taken together (p = 0.007) but not in the PE group alone. Fluoxetine stimulated objectively but not subjectively measured erectile response during laboratory assessment in all groups. No major side effects were reported. In conclusion, fluoxetine (5-10 mg/day) was effective in increasing latency to ejaculation in patients with PE (PE and PE/ED groups combined). PMID:9472846

  14. Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study.

    PubMed Central

    Amir, J.; Harel, L.; Smetana, Z.; Varsano, I.

    1997-01-01

    OBJECTIVES: To examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children. DESIGN: Randomised double blind placebo controlled study. SETTING: Day care unit of a tertiary paediatric hospital. SUBJECTS: 72 children aged 1-6 years with clinical manifestations of gingivostomatitis lasting less than 72 hours; 61 children with cultures positive for herpes simplex virus finished the study. MAIN OUTCOME MEASURES: Duration of oral lesions, fever, eating and drinking difficulties, and viral shedding. INTERVENTION: Aciclovir suspension 15 mg/kg five times a day for seven days, or placebo. RESULTS: Children receiving aciclovir had oral lesions for a shorter period than children receiving placebo (median 4 v 10 days (difference 6 days, 95% confidence interval 4.0 to 8.0)) and earlier disappearance of the following signs and symptoms: fever (1 v 3 days (2 days, 0.8 to 3.2)); extraoral lesions (lesions around the mouth but outside the oral cavity) (0 v 5.5 days (5.5 days, 1.3 to 4.7)); eating difficulties (4 v 7 days (3 days, 1.31 to 4.69)); and drinking difficulties (3 v 6 days (3 days, 1.1 to 4.9)). Viral shedding was significantly shorter in the group treated with aciclovir (1 v 5 days (4 days, 2.9 to 5.1)). CONCLUSIONS: Oral aciclovir treatment for herpetic gingivostomatitis, started within the first three days of onset, shortens the duration of all clinical manifestations and the infectivity of affected children. Further studies are needed to evaluate the ideal dose and length of treatment. PMID:9224082

  15. Randomized Placebo-Controlled Study Evaluating Lateral Branch Radiofrequency Denervation for Sacroiliac Joint Pain

    PubMed Central

    Cohen, Steven P.; Hurley, Robert W.; Buckenmaier, Chester C.; Kurihara, Connie; Morlando, Benny; Dragovich, Anthony

    2009-01-01

    Background Sacroiliac joint pain is a challenging condition accounting for approximately 20% of cases of chronic low back pain. Currently, there are no effective long-term treatment options for sacroiliac joint pain. Methods A randomized, placebo-controlled study was conducted in 28 patients with injection-diagnosed sacroiliac joint pain. Fourteen patients received L4-5 primary dorsal rami and S1-3 lateral branch radiofrequency denervation using cooling-probe technology following a local anesthetic block, and 14 patients received the local anesthetic block followed by placebo denervation. Patients who failed to respond to placebo injections crossed over and were treated with radiofrequency denervation using conventional technology. Results One, 3 and 6-months post-procedure, 11 (79%), 9 (64%) and 8 (57%) of radiofrequency treated patients experienced ≥ 50% pain relief and significant functional improvement. In contrast, only 2 (14%) patients in the placebo group experienced significant improvement at their 1-month follow-up, and none experienced benefit 3-months post-procedure. In the crossover group (n=11), 7 (64%), 6 (55%) and 4 (36%) patients experienced improvement 1, 3 and 6-months post-procedure. One year after treatment, only 2 (14%) patients in the treatment group continued to demonstrate persistent pain relief. Conclusions These results provide preliminary evidence that L4 and L5 primary dorsal rami and S1-3 lateral branch radiofrequency denervation may provide intermediate-term pain relief and functional benefit in selected patients with suspected sacroiliac joint pain. Larger studies are needed to confirm our results, and determine the optimal candidates and treatment parameters for this poorly understood disorder. PMID:18648237

  16. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy

    PubMed Central

    Kessler, John A; Smith, A Gordon; Cha, Bong-Soo; Choi, Sung Hee; Wymer, James; Shaibani, Aziz; Ajroud-Driss, Senda; Vinik, Aaron

    2015-01-01

    Objective To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy. Methods In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density. Results There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain. Interpretation VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin. PMID:26000320

  17. Risperidone in children with autism: randomized, placebo-controlled, double-blind study.

    PubMed

    Nagaraj, Ravishankar; Singhi, Pratibha; Malhi, Prahbhjot

    2006-06-01

    Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Children's Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated. PMID:16948927

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

    PubMed Central

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

    1995-01-01

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

  19. 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

  20. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis

    PubMed Central

    Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

    2015-01-01

    Background Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Methods Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. Results The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Conclusions Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Trial registration number Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40. PMID:26688732

  1. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study

    PubMed Central

    Schrader, Harald; Stovner, Lars Jacob; Helde, Grethe; Sand, Trond; Bovim, Gunnar

    2001-01-01

    Objective To determine the efficacy of an angiotensin converting enzyme inhibitor in the prophylaxis of migraine. Design Double blind, placebo controlled, crossover study. Setting Neurological outpatient clinic. Participants Sixty patients aged 19-59 years with migraine with two to six episodes a month. Interventions Treatment period of 12 weeks with one 10 mg lisinopril tablet once daily for one week then two 10 mg lisinopril tablets once daily for 11 weeks, followed by a two week wash out period. Second treatment period of one placebo tablet once daily for one week and then two placebo tablets for 11 weeks. Thirty participants followed this schedule, and 30 received placebo followed by lisinopril. Main outcome measures Primary end points: number of hours with headache, number of days with headache, number of days with migraine. Secondary end points: headache severity index, use of drugs for symptomatic relief, quality of life and number of days taken as sick leave, acceptability of treatment. Results In the 47 participants with complete data, hours with headache, days with headache, days with migraine, and headache severity index were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to 30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril compared with placebo. Days with migraine were reduced by at least 50% in 14 participants for active treatment versus placebo and 17 patients for active treatment versus run-in period. Days with migraine were fewer by at least 50% in 14 participants for active treatment versus placebo. Intention to treat analysis of data from 55 patients supported the differences in favour of lisinopril for the primary end points. Conclusion The angiotensin converting enzyme inhibitor, lisinopril, has a clinically important prophylactic effect in migraine. PMID:11141144

  2. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

    NASA Technical Reports Server (NTRS)

    Jankovic, J.; Gilden, J. L.; Hiner, B. C.; Kaufmann, H.; Brown, D. C.; Coghlan, C. H.; Rubin, M.; Fouad-Tarazi, F. M.

    1993-01-01

    PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

  3. Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies.

    PubMed

    Hofmann, Stefan G; Fang, Angela; Brager, Daniel N

    2015-08-30

    Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges' g=0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. PMID:26094200

  4. Rivastigmine for mild cognitive impairment in Parkinson disease: a placebo-controlled study.

    PubMed

    Mamikonyan, Eugenia; Xie, Sharon X; Melvin, Emilie; Weintraub, Daniel

    2015-06-01

    Mild cognitive impairment (MCI) in Parkinson's disease (PD) may be associated with subtle functional impairment and worse quality of life. The objective of this study was to determine the efficacy and tolerability of rivastigmine for PD-MCI. Patients with PD-MCI (n = 28) were enrolled in a 24-week, randomized, double-blind, placebo-controlled, crossover, single-site study of the rivastigmine transdermal patch. The primary outcome measure was the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). Secondary outcomes included the Montreal Cognitive Assessment (MoCA), Dementia Rating Scale-2 (DRS-2), Neurotrax computerized cognitive battery, the Everyday Cognition Battery (ECB), and the Parkinson's Disease Questionnaire (PDQ-8). Twenty-six participants (92.9%) completed both study phase assessments, and 23 (82.1%) completed both phases on study medication. The CGIC response rate demonstrated a trend effect in favor of rivastigmine (regression coefficient for interaction term in linear mixed-effects model = 0.44, F[df] = 3.01 [1, 24], P = 0.096). For secondary outcomes, a significant rivastigmine effect on the ECB (regression coefficient = -2.41, F[df] = 5.81 [1, 22.05], P = 0.03) was seen, but no treatment effect was found on any cognitive measures. Trend effects also occurred in favor of rivastigmine on the PDQ-8 (regression coefficient = 4.55, F[df] = 3.93 [1, 14. 79], P = 0.09) and the State Anxiety Inventory (regression coefficient = -1.24, F[df] = 3.17 [1, 33], P = 0.08). Rivastigmine in PD-MCI showed a trend effect for improvements on a global rating of cognition, disease-related health status, and anxiety severity, and significant improvement on a performance-based measure of cognitive abilities. © 2015 International Parkinson and Movement Disorder Society. PMID:25914281

  5. A Double-Blind, Placebo-Controlled Study of Selegiline Transdermal System in Depressed Adolescents

    PubMed Central

    Hochadel, Thomas J.; Portland, Kimberly Blanchard; Azzaro, Albert J.; Katic, Alain; Khan, Arif; Emslie, Graham

    2014-01-01

    Abstract Objective: A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12–17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features. Methods: Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions – Severity (CGI-S) and Clinical Global Impressions – Improvement (CGI-I). Results: Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial. Conclusions: These data demonstrated that

  6. Perilla Extract improves gastrointestinal discomfort in a randomized placebo controlled double blind human pilot study

    PubMed Central

    2014-01-01

    Background Gastrointestinal (GI) discomfort, e.g. bloating or rumbling, is a common symptom in otherwise healthy adults. Approximately 20% of the population, particularly women suffer from gastrointestinal discomfort and this affects quality of life. Recent studies discovered a link between the body and mind, called the gut-brain axis. Psychosocial factors, such as e.g. daily stress may cause altered gut physiology leading to ileum contractions and consequently gastrointestinal symptoms. In vitro and ex vivo studies clearly showed that a Perilla frutescens extract combines prokinetic, antispasmodic and anti-inflammatory effects. The aim of the intervention was to investigate the effects of the proprietary Perilla extract on GI discomfort in healthy subjects with gastrointestinal discomfort and reduced bowel movements in comparison to a placebo product. Methods The pilot study was performed according to a double-blind, randomized, placebo-controlled parallel design. Fifty healthy subjects with gastrointestinal discomfort and reduced bowel movements, 30-70 years, documented their GI symptoms, stool frequency and consistency daily during a 2-week run-in phase and a 4-week intervention phase with Perilla frutescens extract or placebo. GI symptoms were assessed on a 5-point scale daily and average scores over 14 days intervals were calculated. Results All GI symptoms were significantly improved over time by Perilla frutescens extract during the intervention phase (bloating: -0.44 ± 0.56, p = 0.0003; passage of gas: -0.30 ± 0.66, p = 0.0264; GI rumbling: -0.55 ± 0.87, p = 0.0014; feeling of fullness: -0.36 ± 0.72, p = 0.0152; abdominal discomfort: -0.54 ± 0.75, p = 0.004), whereas in the placebo group only abdominal discomfort was significantly improved (-0.31 ± 0.55, p = 0.0345). In the subgroup of women results were strengthened and a subscore out of bloating and abdominal discomfort was significantly improved

  7. Intravenous Micronutrient Therapy (Myers' Cocktail) for Fibromyalgia: A Placebo-Controlled Pilot Study

    PubMed Central

    Ali, Ather; Njike, Valentine Yanchou; Northrup, Veronika; Sabina, Alyse B.; Williams, Anna-Leila; Liberti, Lauren S.; Perlman, Adam I.; Adelson, Harry

    2009-01-01

    Abstract Objectives Intravenous micronutrient therapy (IVMT), and specifically the Myers' Cocktail, is a popular approach for treating fibromyalgia syndrome (FMS) among complementary and alternative medicine practitioners, but its efficacy is uncertain. This trial assessed the feasibility, safety, and provided insights into the efficacy of this therapy. Design This was a randomized, double-blind, placebo-controlled pilot study. Locations The study locations were an academic research center, teaching hospital, and affiliated Integrative Medicine Center in Derby, CT. Subjects The subjects were 34 adults with American College of Rheumatology (ACR)-defined FMS. Intervention Subjects were randomly assigned either to treatment (weekly infusions of IVMT) or to placebo (weekly infusions of lactated Ringer's solution) for 8 weeks. Outcome measures Primary outcome was change in the Tender Point Index, assessed 8 and 12 weeks after initiation. Secondary measures included a Visual Analog Scale to assess global pain, and validated measures of physical function (Fibromyalgia Impact Questionnaire), mood (Beck Depression Index), and quality of life (Health Status Questionnaire 2.0). Results Clinically significant improvements were noted (of a magnitude similar to other effective interventions). However, in part because of the high placebo response and the small sample size, no statistically significant differences were seen between groups, in any outcome measure, at 8 and 16 weeks. Statistically significant within-group differences were seen in both the intervention and placebo groups, demonstrating a treatment effect for both IVMT and placebo. At 8 weeks, the IVMT group experienced significantly improved tender points, pain, depression, and quality of life directly following treatment (all p ≤ 0.02), while the placebo group experienced significantly improved tender points only (p ≤ 0.05). The treatment effects of IVMT persisted at 4 weeks postintervention for tender

  8. 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

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

    PubMed

    Schilling, J; Mueller, R S

    2012-07-28

    Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs. PMID:22678620

  10. Major depressive disorder with subthreshold hypomania (mixed features): Clinical characteristics of patients entered in a multiregional, placebo-controlled study.

    PubMed

    Targum, Steven D; Suppes, Trisha; Pendergrass, J Cara; Lee, Sang; Silva, Robert; Cucchiaro, Josephine; Loebel, Antony

    2016-07-01

    Major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features), has been identified as a distinct nosological entity in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We identified the predominant manic symptoms present at baseline in a multiregional, placebo-controlled trial involving 211 patients with MDD with mixed features (Clinicaltrials.govNCT01421134). Patients with 2 or 3 DSM-5 criteria defined manic symptoms were eligible for the study. At study baseline, increased talkativeness (pressure to keep talking) and flight of ideas (racing thoughts) were endorsed by approximately 65% of patients and a decreased need for sleep was endorsed by 40% of patients. Approximately 60% of patients also endorsed irritability and distractibility at baseline although these symptoms are not generally counted as part of the "mixed" depression diagnosis as they may overlap with criteria for MDD. Thus, five clinical symptoms characterized the manic presentation in the majority of patients diagnosed as having MDD with "mixed" features in this first placebo-controlled trial examining the use of a psychotropic medication (lurasidone) in this population. Our findings support the designation of MDD with mixed features specifier and suggest that this subpopulation of depressed patients may warrant additional medication beyond antidepressants. PMID:26908089

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

    PubMed

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

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration. PMID:27070542

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

    PubMed Central

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

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants’ (unwarranted) reliance on their partners’ opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other’s performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration. PMID:27070542

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

    PubMed Central

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

    2013-01-01

    Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M, Haytac MC. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol 2013; 40: 1025–1035. doi: 10.1111/jcpe.12155. AimThe aim of this randomized placebo-controlled clinical trial was to evaluate the effects of Lactobacillus reuteri-containing probiotic lozenges as an adjunct to scaling and root planing (SRP). Material and MethodsThirty chronic periodontitis patients were recruited and monitored clinically and microbiologically at baseline, 3, 6, 9 and 12 weeks after therapy. All patients received one-stage full-mouth disinfection and randomly assigned over a test (SRP + probiotic, n = 15) or control (SRP + placebo, n = 15) group. The lozenges were used two times a day for 12 weeks. ResultsAt week 12, all clinical parameters were significantly reduced in both groups, while there was significantly more pocket depth reduction (p < 0.05) and attachment gain (p < 0.05) in moderate and deep pockets; more Porphyromonas gingivalis reduction was observed in the SRP + probiotic group. ConclusionsThe results indicate that oral administration of L. reuteri lozenges could be a useful adjunct to SRP in chronic periodontitis. PMID:24164569

  14. 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

  15. A double-blinded, placebo-controlled trial of garlic as a mosquito repellant: a preliminary study.

    PubMed

    Rajan, T V; Hein, M; Porte, P; Wikel, S

    2005-03-01

    The hypothesis that the ingestion of garlic provides protection against bloodsucking pests such as mosquitoes was investigated using a randomized, double-blinded, placebo-controlled crossover study. Subjects were asked to consume either garlic (one visit) or a placebo (the other visit). They were then exposed to laboratory-reared Aedes aegypti (Linnaeus) (Diptera: Culicidae). The numbers of mosquitoes that did not feed on the subjects, the number of mosquito bites, the weights of the mosquitoes after feeding and the amounts of blood ingested were determined. The data did not provide evidence of significant systemic mosquito repellence. A limitation of the study is that more prolonged ingestion of garlic may be needed to accomplish repellence. PMID:15752181

  16. The effect of oral nitroglycerin on portal blood velocity as measured by ultrasonic Doppler. A double blind, placebo controlled study.

    PubMed

    Yang, S S; Ralls, P W; Korula, J

    1991-04-01

    We studied the effect of oral nitroglycerin on portal blood velocity (PBV) in 20 cirrhotic patients by a double blind, placebo controlled method using noninvasive Doppler sonography. After we obtained baseline Doppler in the fasting state, 0.6 mg nitroglycerin or placebo was given orally and the mean of 3 s averaged mean PBVs was repeated at 5 min intervals for 60 min. Ten patients each received nitroglycerin or placebo. Portal vein flows were antegrade in all. Of the 10 patients receiving nitroglycerin, seven (P = 0.002) showed a greater than 10% fall in the mean PBVs for at least 15 min. Of these seven "responders," five patients had a 10% decrease in mean systemic blood pressure for at least 15 min. None of the "nonresponders" had systemic hypotension. Our study suggests that the PBV-reducing effect of nitroglycerin in cirrhotics may be explained in part by systemic hypotension. PMID:1903409

  17. Topical capsaicin—a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study

    PubMed Central

    Lysy, J; Sistiery-Ittah, M; Israelit, Y; Shmueli, A; Strauss-Liviatan, N; Mindrul, V; Keret, D; Goldin, E

    2003-01-01

    Purpose: Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with capsaicin. Methods: Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with capsaicin treatment in an open labelled manner. Results: Thirty one of 44 patients experienced relief during capsaicin treatment periods and did not respond to menthol; all patients not responding to capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with capsaicin was unsuccessful: eight patients did not respond to capsaicin treatment, one responded equally to capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 “responders” needed a mean application of capsaicin every day (1.6 (SD 1.2); range 0.5–7 days) to remain symptom free (or nearly symptom free). Conclusion: Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani. PMID:12912865

  18. A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study

    ERIC Educational Resources Information Center

    Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O'Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

    2011-01-01

    Objective: The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. Method: Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive…

  19. Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study.

    PubMed

    Lyritis, G P; Paspati, I; Karachalios, T; Ioakimidis, D; Skarantavos, G; Lyritis, P G

    1997-10-01

    We examined the analgesic effect of nasal salmon calcitonin in patients with acute pain due to recent, nontraumatic osteoporotic vertebral crush fractures. 32 men and 68 postmenopausal women were studied using a prospective, double-blind, placebo-controlled clinical design. Men and women taking 200 IU of nasal salmon calcitonin daily for a period of 28 days had a dramatic decrease of spinal pain. This analgesic effect was accompanied by early mobilization and gradual restoration of the locomotor functions, such as sitting, standing and walking. Patients receiving the placebo nasal spray remained in bed for almost the entire period of observation. The consumption of high doses of paracetamol did not help placebo patients to get out of bed during the 4 weeks of hospitalization. Nasal salmon calcitonin and early mobilization also reduced hydroxyproline excretion, thus preventing massive bone loss during the period of bedrest. PMID:9385283

  20. Effectiveness of Ramelteon for Insomnia Symptoms in Older Adults with Obstructive Sleep Apnea: A Randomized Placebo-Controlled Pilot Study

    PubMed Central

    Gooneratne, Nalaka S.; Gehrman, Philip; Gurubhagavatula, Indira; Al-Shehabi, Erica; Marie, Elisabeth; Schwab, Richard

    2010-01-01

    Study Objectives: To evaluate the effectiveness of ramelteon, a melatonin receptor agonist, for the treatment of insomnia in older adults starting auto-titrating positive airway pressure (APAP) therapy for sleep apnea. Methods: A parallel group, randomized, double-blind, placebo-controlled pilot effectiveness clinical trial. The study enrolled 21 research study participants who were ≥ 60 years old and had obstructive sleep apnea, defined by an apnea-hypopnea index (AHI) ≥ 5 events/h, with complaints of insomnia. The primary outcome measure was change in sleep onset latency determined from polysomnography at 4 weeks. Research study participants, all of whom were starting on APAP, were randomized to ramelteon 8 mg (n = 8) or placebo (n = 13). Results: Ramelteon treatment was associated with a statistically significant difference in sleep onset latency (SOL) as measured by polysomnography of 28.5 min (± 16.2 min) compared to placebo (95% C.I. 8.5 min to 48.6 min, effect size 1.35, p = 0.008). This was due to a 10.7 (± 17.0) min SOL reduction in the ramelteon arm and a 17.8 (± 23.5) min SOL increase in the placebo arm. No change was noted in subjective sleep onset latency (−1.3 min, ± 19.3 min, 95% C.I.: −21.4 min to 18.7 min). No statistically significant changes were noted in the AHI, sleep efficiency (polysomnography and self-report), APAP adherence, Pittsburgh Sleep Quality Index global score, or Epworth Sleepiness Scale score when comparing ramelteon vs. placebo. Four adverse events occurred in the ramelteon arm and 2 in the placebo arm; none were considered to be related to treatment. Conclusions: Ramelteon was effective in improving objective, but not subjective, sleep onset latency even in older adults who were starting APAP therapy for sleep apnea. Further research is warranted in examining the role of ramelteon in the care of older adults with insomnia symptoms and sleep apnea. Citation: Gooneratne NS; Gehrman P; Gurubhagavatula I; Al-Shehabi E

  1. 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. PMID:23656173

  2. High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study.

    PubMed

    Findling, R L; Maxwell, K; Scotese-Wojtila, L; Huang, J; Yamashita, T; Wiznitzer, M

    1997-08-01

    Several reports have described salutary effects such as decreased physical aggression and improved social responsiveness being associated with the administration of high doses of pyridoxine and magnesium (HDPM) in open-labeled and controlled studies of patients with autism. Despite this fact, this intervention remains controversial. A 10-week double-blind, placebo-controlled trial was undertaken to examine both the efficacy and safety of HDPM in autism. Twelve patients were enrolled, and 10 patients (mean age 6 years 3 months) were able to complete the study. HDPM at an average dose of 638.9 mg of pyridoxine and 216.3 mg of magnesium oxide was ineffective in ameliorating autistic behaviors as assessed by the Children's Psychiatric Rating Scale (CPRS), the Clinical Global Impression Scale, and the NIMH Global Obsessive Compulsive Scale. Furthermore, no clinically significant side effects were noted during HDPM administration. A trend for a transient change on the CPRS was found that was possibly due to a placebo response. This study raises doubts about the clinical effectiveness of HDPM in autistic disorder. PMID:9261669

  3. The natural course of uncomplicated lower urinary tract infection in women illustrated by a randomized placebo controlled study.

    PubMed

    Ferry, Sven A; Holm, Stig E; Stenlund, Hans; Lundholm, Rolf; Monsen, Tor J

    2004-01-01

    This prospective, multicentre, randomized, double-blind and placebo controlled study was performed to describe the natural course of uncomplicated lower urinary tract infection (UTI). A total of 1143 women 18 y and above, consulting at 18 primary health care centres in northern Sweden for symptoms suggestive of UTI were included. The symptoms urgency, dysuria, suprapubic pain and loin pain were registered, and urine cultures performed at inclusion and follow-up visits 8-10 d and 5-7 weeks later. Associations between all symptoms and bacteriuria or bacterial counts were unpredictable. Eradication of symptoms and bacteriuria and combinations of them were studied in 288 patients placebo treated for 7 d, of whom 39% dropped out after the first follow-up visit. The spontaneous cure rate of symptoms was 28% after the first week, and 37% had neither symptoms nor bacteriuria after 5-7 weeks. Considering the high dropout rate after the first follow-up visit, the spontaneous cure rate of symptoms and bacteriuria was calculated to 24% at the end of study. We conclude that patient near-laboratory tests are required to establish the diagnosis of lower UTI, and the guidelines for diagnosis of UTI need to be revised. PMID:15198188

  4. 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

  5. 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

  6. Ginger Supplementation in Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

    PubMed Central

    Rahimlou, Mehran; Yari, Zahra; Hekmatdoost, Azita; Alavian, Seyed Moayed; Keshavarz, Seyed Ali

    2016-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenesis of this disease is closely associated with obesity and insulin resistance. Ginger can have hypolipidemic and antioxidant effects, and act as an insulinsensitizer. Objectives: The aim of this study was to evaluate the effects of ginger supplementation in NAFLD management. Patients and Methods: In a randomized, double-blind, placebo-controlled clinical trial, 44 patients with NAFLD were assigned to take either two grams per day of a ginger supplement or the identical placebo, for 12 weeks. In both groups, patients were advised to follow a modified diet and physical activity program. The metabolic parameters and indicators of liver damage were measured at study baseline and after the 12 week intervention. Results: Ginger supplementation resulted in a significant reduction in alanine aminotransferase, γ-glutamyl transferase, inflammatory cytokines, as well as the insulin resistance index and hepatic steatosis grade in comparison to the placebo. We did not find any significant effect of taking ginger supplements on hepatic fibrosis and aspartate aminotransferase. Conclusions: Twelve weeks of two grams of ginger supplementation showed beneficial effects on some NAFLD characteristics. Further studies are recommended to assess the long-term supplementation effects. PMID:27110262

  7. Effects of daily treatment with citicoline: A double-blind, placebo-controlled study in cocaine-dependent volunteers

    PubMed Central

    Licata, S.C.; Penetar, D. M.; Ravichandran, C.; Rodolico, J.; Palmer, C.; Berko, J.; Geaghan, T.; Looby, A.; Peters, E.; Ryan, E.; Renshaw, P.F.; Lukas, S.E.

    2011-01-01

    Many pharmacotherapies for treating cocaine dependence are aimed at reducing drug effects, alleviating craving, and/or preventing relapse. We demonstrated previously that citicoline, a compound used to repair neuronal damage in stroke and brain injury, is safe in cocaine-abusing volunteers. Objectives This study assessed the effectiveness of an eight-week citicoline treatment period and four-week follow-up in cocaine-dependent individuals. Methods Twenty-nine healthy non-treatment-seeking cocaine-dependent male and female volunteers were randomized in this double-blind, placebo-controlled study, eighteen of whom completed the treatment period of the study. Participants took citicoline (500 mg b.i.d) or matched placebo each day, and recorded measures of craving and drug use. Participants visited the laboratory twice a week for urine screens, as well as to attend weekly group therapy sessions. Results Citicoline had no effect on cocaine craving or total use. Conclusions While the current preliminary results from this small trial suggest that citicoline is not an effective treatment for heavy cocaine users, further investigation of citicoline’s efficacy as a treatment for substance dependence in other settings may be warranted. PMID:21769048

  8. Consumption of glucose drinks slows sensorimotor processing: double-blind placebo-controlled studies with the Eriksen flanker task

    PubMed Central

    Hope, Christopher; Seiss, Ellen; Dean, Philip J. A.; Williams, Katie E. M.; Sterr, Annette

    2013-01-01

    Modulations of blood glucose concentration (BGC) in the normal range are known to facilitate performance in memory and other cognitive tasks but few studies have investigated the effects of BGC variations on complex sensorimotor task so far. The present study aimed to examine glucose effects with the Eriksen flanker task. This task was chosen because it can dissociate between the effects of BGC on sensorimotor processing and cognitive control by assessing congruency effects. In two linked double-blind placebo-controlled experiments BGC was elevated within the normal BGC range (4–7 mmol/l) by approx. 1.5 mmol/l with glucose drinks and compared to a placebo drink condition while a flanker task with either strong or weak stimulus-response (SR) mapping was performed. Modulation of the performance in the flanker task by glucose was linked to the strength of the SR mapping but not congruency effects. Under weak SR mapping, reaction times (RTs) were slowed in the glucose condition compared to placebo while error rates remained unchanged, whereas cognitive control was not affected by glucose. When SR mapping was strong, no differences were found between glucose and placebo. Enhanced glucose levels differentially affect behavior. Whereas the literature mainly reports facilitating characteristics of enhanced glucose levels in the normal range, the present study shows that higher glucose levels can slow RTs. This suggests that glucose does not have a uniform effect on cognition and that it might be differential depending on the cognitive domain. PMID:24167479

  9. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: A randomized placebo-controlled phase III study

    SciTech Connect

    Buentzel, Jens . E-mail: jens.buentzel@shk-ndh.de; Micke, Oliver; Adamietz, Irenaus A.; Monnier, Alain; Glatzel, Michael; Vries, Alexander de

    2006-03-01

    Purpose: Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer. Methods and Materials: Patients from European and American study centers received i.v. amifostine 300 mg/m{sup 2} (n = 67) or placebo (n = 65) before carboplatin 70 mg/m{sup 2} and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m{sup 2} or placebo before radiotherapy on other days. Results: Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments. Conclusions: The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.

  10. Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study.

    PubMed

    Geha, R S; Beiser, A; Ren, C; Patterson, R; Greenberger, P A; Grammer, L C; Ditto, A M; Harris, K E; Shaughnessy, M A; Yarnold, P R; Corren, J; Saxon, A

    2000-04-01

    Monosodium glutamate (MSG) has a long history of use in foods as a flavor enhancer. In the United States, the Food and Drug Administration has classified MSG as generally recognized as safe (GRAS). Nevertheless, there is an ongoing debate exists concerning whether MSG causes any of the alleged reactions. A complex of symptoms after ingestion of a Chinese meal was first described in 1968. MSG was suggested to trigger these symptoms, which were referred to collectively as Chinese Restaurant Syndrome. Numerous reports, most of them anecdotal, were published after the original observation. Since then, clinical studies have been performed by many groups, with varying degrees of rigor in experimental design ranging from uncontrolled open challenges to double-blind, placebo controlled (DBPC) studies. Challenges in subjects who reported adverse reactions to MSG have included relatively few subjects and have failed to show significant reactions to MSG. Results of surveys and of clinical challenges with MSG in the general population reveal no evidence of untoward effects. We recently conducted a multicenter DBPC challenge study in 130 subjects (the largest to date) to analyze the response of subjects who report symptoms from ingesting MSG. The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, the frequency of the responses was low and the responses reported were inconsistent and were not reproducible. The responses were not observed when MSG was given with food. PMID:10736382

  11. Placebo-Controlled Trials in Surgery

    PubMed Central

    Probst, Pascal; Grummich, Kathrin; Harnoss, Julian C.; Hüttner, Felix J.; Jensen, Katrin; Braun, Silvia; Kieser, Meinhard; Ulrich, Alexis; Büchler, Markus W.; Diener, Markus K.

    2016-01-01

    Abstract This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials. Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. “Surgical procedure” was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment. Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92–2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials. Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made. PMID:27124060

  12. A Randomized, Double-blind, Placebo-Controlled Study of Efficacy of Oral Acyclovir in the Treatment of Pityriasis Rosea

    PubMed Central

    2014-01-01

    Background: Pityriasis rosea is an acute self-limiting skin disorder of unknown aetiology. Recently human herpes virus 6 and 7 has been hypothesized to be the cause of pityriasis rosea. Objective: To determine the efficacy of acyclovir, an anti-viral drug, in the treatment of pityriasis rosea. Materials and Methods: A randomized, double-blind, placebo-controlled study of efficacy of oral acyclovir in the treatment of pityriasis rosea was conducted on 73 patients. Thirty eight randomly selected patients were started on oral acyclovir. Thirty-five patients were prescribed placebo. The patients as well as the chief investigator were unaware of the therapeutic group to which patients belonged (acyclovir or placebo). Patients in both the groups were evaluated clinically after 7 and 14 days following the first visit and the data were analysed. Results: Follow up data of 60 patients was available and these were included in the statistical analysis. 53.33% and 86.66% of the patients belonging to the acyclovir group showed complete resolution on the 7th day and 14th day respectively following the first visit compared to 10% and 33.33% of patients from the placebo group. The findings were statistically significant. Conclusion: The study showed that high dose acyclovir is effective in the treatment of pityriasis rosea. PMID:24995231

  13. 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

  14. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract.

    PubMed

    Kaats, Gilbert R; Miller, Howard; Preuss, Harry G; Stohs, Sidney J

    2013-05-01

    Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are widely consumed in dietary supplements for weight management and sports performance. p-Synephrine is also present in foods derived from a variety of Citrus species. Bitter orange extract is commonly used in combination with multiple herbal ingredients. Most clinical studies conducted on bitter orange extract alone have involved single doses. The purpose of this study was to assess the safety of bitter orange extract (approximately 49mg p-synephrine) alone or in combination with naringin and hesperidin twice daily given to 25 healthy subjects per group for 60days in a double-blinded, placebo-controlled protocol. No significant changes occurred in systolic or diastolic blood pressures, blood chemistries or blood cell counts in control or p-synephrine treated groups. Small, clinically insignificant differences in heart rates were observed between the p-synephrine plus naringin and hesperidin group and the p-synephrine alone as well as the placebo group. No adverse effects were reported in the three groups. Bitter orange extract and p-synephrine appear to be without adverse effects at a dose of up to 98mg daily for 60days based on the parameters measured. PMID:23354394

  15. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults.

    PubMed

    Rainey-Smith, Stephanie R; Brown, Belinda M; Sohrabi, Hamid R; Shah, Tejal; Goozee, Kathryn G; Gupta, Veer B; Martins, Ralph N

    2016-06-01

    Curcumin therapy in animals has produced positive cognitive and behavioural outcomes; results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. Individuals (n 96) ingested either placebo or 1500 mg/d BiocurcumaxTM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis; time×treatment; F=3·85, P<0·05). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration. PMID:27102361

  16. 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

  17. Erotic Stimulus Processing under Amisulpride and Reboxetine: A Placebo-Controlled fMRI Study in Healthy Subjects

    PubMed Central

    Wiegers, Maike; Metzger, Coraline D.; Walter, Martin; Grön, Georg; Abler, Birgit

    2015-01-01

    Background: Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Methods: Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Results: Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. Conclusions: In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. PMID:25612894

  18. Testosterone and estrogen impact social evaluations and vicarious emotions: A double-blind placebo-controlled study.

    PubMed

    Olsson, Andreas; Kopsida, Eleni; Sorjonen, Kimmo; Savic, Ivanka

    2016-06-01

    The abilities to "read" other peoples' intentions and emotions, and to learn from their experiences, are critical to survival. Previous studies have highlighted the role of sex hormones, notably testosterone and estrogen, in these processes. Yet it is unclear how these hormones affect social cognition and emotion using acute hormonal administration. In the present double-blind placebo-controlled study, we administered an acute exogenous dose of testosterone or estrogen to healthy female and male volunteers, respectively, with the aim of investigating the effects of these steroids on social-cognitive and emotional processes. Following hormonal and placebo treatment, participants made (a) facial dominance judgments, (b) mental state inferences (Reading the Mind in the Eyes Test), and (c) learned aversive associations through watching others' emotional responses (observational fear learning [OFL]). Our results showed that testosterone administration to females enhanced ratings of facial dominance but diminished their accuracy in inferring mental states. In men, estrogen administration resulted in an increase in emotional (vicarious) reactivity when watching a distressed other during the OFL task. Taken together, these results suggest that sex hormones affect social-cognitive and emotional functions at several levels, linking our results to neuropsychiatric disorders in which these functions are impaired. (PsycINFO Database Record PMID:26751627

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

    PubMed

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

    2001-03-01

    Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has proven to be effective in various pain syndromes such as renal colic and muscular pain. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of oral LC compared to placebo in the acute treatment of migraine. Sixty four patients with the diagnosis of migraine, according to the IHS criteria, were studied prospectively. Patients received LC or placebo once the headache reached moderate or severe intensity for 6 consecutive attacks. With regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4 hours. The consumption of other rescue medications after 4 hours was significantly higher in the placebo group. With regard to the severe attacks, there was no difference between the active drug group and the placebo group concerning headache intensity and consumption of other rescue medications. We conclude that the NSAID lysine clonixinate is effective in treating moderately severe migraine attacks. It is not superior than placebo in treating severe migraine attacks. PMID:11299430

  20. Randomised double-blind placebo-controlled study of the effect of Lactobacillus paracasei NCC 2461 on skin reactivity.

    PubMed

    Gueniche, A; Philippe, D; Bastien, P; Reuteler, G; Blum, S; Castiel-Higounenc, I; Breton, L; Benyacoub, J

    2014-06-01

    In recent decades, the prevalence of subjects with reactive skin has considerably increased in industrialised countries. 50% of women and 30% of men report cutaneous discomfort classified under reactive/sensitive skin. Several topical approaches have been proposed, in particular through improvement of galenic forms or protection of epidermal surface. We propose to act differently, deeply from inside the body via an innovative nutritional approach. To this purpose, Lactobacillus paracasei NCC 2461 (ST11) was selected because of its specific beneficial skin properties discovered in in vitro studies, i.e. diminution of neurogenic inflammation and promotion of the recovery of skin barrier function. We designed a randomised double-blind placebo-controlled clinical study with a two-month supplementation in two female treatment groups (n=32 per group). A capsaicin test was performed to monitor the time course of skin sensitivity. Moreover, transepidermal water loss was assessed to analyse the rate of skin barrier function recovery; dryness of the leg and roughness of the cheeks was investigated by a dermatologist as well as by self-assessment. The results of the present clinical trial show that oral supplementation with the probiotic decreases skin sensitivity and increases the rate of barrier function recovery. Thus, the data provide evidence that daily intake of ST11 could improve reactive skin condition. PMID:24322879

  1. Effect of GutGard in the Management of Helicobacter pylori: A Randomized Double Blind Placebo Controlled Study

    PubMed Central

    Puram, Sreenivasulu; Suh, Hyung Chae; Kim, Seung Un; Bethapudi, Bharathi; Joseph, Joshua Allan; Agarwal, Amit; Kudiganti, Venkateswarlu

    2013-01-01

    A randomized, double blind placebo controlled study was conducted to evaluate the efficacy of GutGard (root extract of Glycyrrhiza glabra) in the management of Helicobacter pylori (H. pylori) gastric load. Participants diagnosed with H. pylori infection were randomly assigned to two groups to orally receive 150 mg of GutGard (n = 55) or placebo (n = 52) once daily for 60 days. H. pylori infection was assessed using 13C-urea breath test (13C-UBT) at days 0, 30, and 60. Stool Antigen test (HpSA) was also performed on days 0, 30, and 60. Repeated measures of analysis of variance (RMANOVA), chi-square, and Fisher's exact probability tests were used to compare the treatment outcomes. A significant interaction effect between group and time (P = 0.00) and significant difference in mean Delta Over Baseline (DOB) values between GutGard (n = 50) and placebo (n = 50) treated groups after intervention period were observed. On day 60, the results of HpSA test were negative in 28 subjects (56%) in GutGard treated group whereas in placebo treated group only 2 subjects (4%) showed negative response; the difference between the groups was statistically significant. On day 60, the results of 13C-UBT were negative in 24 (48%) in GutGard treated group and the difference between the groups was statistically significant. The findings suggest GutGard is effective in the management of H. pylori. PMID:23606875

  2. Once-daily rupatadine improves the symptoms of chronic idiopathic urticaria: a randomised, double-blind, placebo-controlled study.

    PubMed

    Dubertret, Louis; Zalupca, Lavinia; Cristodoulo, Tania; Benea, Vasile; Medina, Iris; Fantin, Sara; Lahfa, Morad; Pérez, Iñaki; Izquierdo, Iñaki; Arnaiz, Eva

    2007-01-01

    This randomised, double-blind, placebo-controlled, parallel-group, international, dose-ranging study investigated the effect of treatment with rupatadine 5, 10 and 20 mg once daily for 4 weeks on symptoms and interference with daily activities and sleep in 12-65 years-old patients with moderate-to-severe chronic idiopathic urticaria (CIU). Rupatadine 10 and 20 mg significantly reduced pruritus severity by 62.05% and 71.87% respectively, from baseline, over a period of 4 weeks compared to reduction with placebo by 46.59% (p < 0.05). Linear trends were noted for reductions in mean number of wheals and interference with daily activities and sleep with rupatadine 10 and 20 mg over the 4-week treatment period. The two most frequently reported AEs were somnolence (2.90% for placebo, 4.29% for 5 mg-, 5.41% for 10 mg- and 21.43% for 20 mg-rupatadine-treated group) and headache (4.35% for placebo, 2.86% for 5 mg-, 4.05% for 10 mg- and 4.29% for 20 mg-rupatadine-treated group). These findings suggest that rupatadine 10 and 20 mg is a fast-acting, efficacious and safe treatment for the management of patients with moderate-to-severe CIU. Rupatadine decreased pruritus severity, in a dose- and time-dependent manner. PMID:17478385

  3. A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression.

    PubMed

    Itil, T M; Shrivastava, R K; Mukherjee, S; Coleman, B S; Michael, S T

    1983-01-01

    1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. Fluvoxamine exhibited fewer anticholinergic side effects than imipramine. 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients, as measured using the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter. PMID:6407504

  4. The effects of polyunsaturated fatty acids in alcohol dependence treatment - a double-blind, placebo-controlled pilot study

    PubMed Central

    2011-01-01

    Background The lipid fraction of cell membranes consists of polyunsaturated fatty acids (PUFAS), and chronic alcohol use alters it, modifying its permeability, what might contribute for the dysfunctional metabolism observed in the central nervous system of alcohol dependent patients. Therefore, the supplementation of PUFAS can be an important adjuvant in alcoholism treatment. Methods This was a placebo controlled, double blind, randomized study where, 80 alcohol dependent patients, according to DSM-IV, were allocated in four groups with 20 patient each: 'PUFAS', 'Naltrexone', 'Naltrexone + PUFAS' and 'Placebo'. Those substances were administered for 90 days and scales were applied to assess patients craving (OCDS) and alcohol dependence severity (SADD) at baseline and after 90 days. PUFAS serum levels were assessed before and after treatment by high performance liquid chromatography assay. Results Forty-three patients completed the trial. There was a significant improvement over time on drinking days, SADD and OCDS scores in all groups (p < 0.001). The drinking days comparison between groups did not show statistical significant difference. The same effect was observed for compulsion (OCDS) and severity of dependence scale (SADD). The serum levels of PUFAS increased in all the supplemented groups after treatment, although not significantly. Conclusions The oral supplementation of 2 g PUFAS for 3 months did not significantly differ from placebo in reducing the amount of alcohol ingestion, or OCDS and SADD scores in a group of alcohol dependent patient. Trial registration NCT01211769 PMID:21787433

  5. 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

  6. No Evidence of Intelligence Improvement after Working Memory Training: A Randomized, Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Redick, Thomas S.; Shipstead, Zach; Harrison, Tyler L.; Hicks, Kenny L.; Fried, David E.; Hambrick, David Z.; Kane, Michael J.; Engle, Randall W.

    2013-01-01

    Numerous recent studies seem to provide evidence for the general intellectual benefits of working memory training. In reviews of the training literature, Shipstead, Redick, and Engle (2010, 2012) argued that the field should treat recent results with a critical eye. Many published working memory training studies suffer from design limitations…

  7. 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

  8. Melatonin Treatment in Individuals with Intellectual Disability and Chronic Insomnia: A Randomized Placebo-Controlled Study

    ERIC Educational Resources Information Center

    Braam, W.; Didden, R.; Smits, M.; Curfs, L.

    2008-01-01

    Background: While several small-number or open-label studies suggest that melatonin improves sleep in individuals with intellectual disabilities (ID) with chronic sleep disturbance, a larger randomized control trial is necessary to validate these promising results. Methods: The effectiveness of melatonin for the treatment of chronic sleep…

  9. Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus

    PubMed Central

    Viscusi, Eugene R.; Rathmell, James P.; Fichera, Alessandro; Binderow, Sander R.; Israel, Robert J.; Galasso, Frank L.; Penenberg, Darryl; Gan, Tong J.

    2013-01-01

    Objective This phase 2 study evaluated the safety and activity of intravenous methylnaltrexone on the duration of postoperative ileus in patients undergoing segmental colectomy. Methods Adults (aged 18 years or older) with American Society of Anesthesiologists physical status of I, II, or III who underwent segmental colectomy, including partial colectomy, sigmoidectomy, cecectomy, or anterior proctosigmoidectomy, via laparotomy with general anesthesia, received intravenous methylnaltrexone 0.30 mg/kg or placebo every 6 h beginning within 90 min after end of surgery. Treatment continued until 24 h after the patient tolerated solid foods, was discharged, or for 7 d maximum. Efficacy endpoints included measures of gastrointestinal recovery and time to discharge eligibility. Results A total of 65 patients (methylnaltrexone, n = 33; placebo, n = 32) were randomized. Mean time to first bowel movement was accelerated by 20 h (p = 0.038) and time to discharge eligibility was accelerated by 33 h (p = 0.049) with methylnaltrexone vs placebo. Opioid use was similar between groups until postoperative day 4, then fluctuated in the placebo group. Methylnaltrexone was generally well tolerated. Conclusions In this study, intravenous methylnaltrexone significantly decreased time to postoperative bowel recovery and eligibility for hospital discharge by ∼1 d, with an adverse event profile similar to placebo. These were two of several exploratory endpoints; not all efficacy endpoints showed a significant difference between methylnaltrexone and placebo. The efficacy results in this trial were not seen in two subsequent large-scale studies.

  10. A placebo-controlled study of memantine (Ebixa) in dementia of Wernicke-Korsakoff syndrome.

    PubMed

    Rustembegović, Avdo; Kundurović, Zlata; Sapcanin, Aida; Sofic, Emin

    2003-01-01

    We evaluated the responses of 16 patients to preliminarily explore the spectrum of effectiveness and tolerability of the memantine, and NMDA antagonist, in the treatment of dementia in Wernicke-Korsakoff syndrome. In this study, for the first time in dementia of Wernicke-Korsakoff syndrome, the response to memantine was assessed. 16 patients with median age of 64 years and median body weight of 77 kg were treated with memantine 10 mg twice daily for up to 28 weeks. Clinical global impressions (CGI), and Mini Mental Status Examination (MMSE) were performed during the treatment period (after 2, 4, and 28 weeks). Efficacy measures also included the ADCS-Activities of Daily Living scale (ADCS-ADL). At 28 weeks, the ADCS-ADL showed significantly less deterioration in memantine treated patients compared with placebo (-2.3 compared with -4.3: p = 0.005). The results of MMSE demonstrate a significant and clinically relevant benefit for memantine relative to placebo as shown by positive outcomes in cognitive and functional assessments. Memantine (10 mg) was safe and well tolerated. The preliminarily findings of this study with 16 patients suggested that memantine is effective in the treatment of dementia in Wernicke-Korsakoff syndrome. PMID:12858653

  11. Can the 8-coil Shakti alter subjective emotional experience? A randomized, placebo-controlled study.

    PubMed

    Gendle, Mathew H; McGrath, Megan G

    2012-02-01

    At present, a commercially available device (the 8-coil Shakti) claims to produce weak and complex magnetic fields that alter neurobiological processes. The effects of the Shakti on emotional responses to photographs that varied on emotional valence were investigated. Participants (N = 37) were exposed to either 30 min, of magnetic fields or a sham condition and rated their emotional reactions to a set of 54 color photographs. Although participants indicated significantly different emotional responses to images with distinct emotional valences, exposure to magnetic fields did not affect these responses, nor significantly interact with image emotional valence. Although the device's "amygdala signal" had no effect on the emotive response to images in this study, additional investigations examining the effects of weak and complex magnetic fields on various aspects of perception and cognition are warranted. PMID:22582690

  12. Postoperative pain management with transdermal fentanyl after forefoot surgery: a randomized, placebo-controlled study

    PubMed Central

    Merivirta, Riika; Pitkänen, Mikko; Alanen, Jouko; Haapoja, Elina; Koivisto, Mari; Kuusniemi, Kristiina

    2015-01-01

    Background Quality of life is decreased in patients with hallux valgus deformity, mainly because of pain. Significant improvement is usually achieved by surgery. However, postoperative pain can be moderate to severe for 2–3 days. The aim of the present study was to evaluate the use of transdermal fentanyl for postoperative pain management after forefoot surgery. Methods Sixty patients undergoing hallux valgus or hallux rigidus surgery were allocated to receive a patch delivering either fentanyl 12 μg/hour or placebo for postoperative pain. The consumption of rescue opioid oxycodone, the primary outcome measure, was evaluated daily until the fourth postoperative day. Total consumption of oxycodone during the study period was also assessed. Pain scores and possible adverse effects were evaluated every 6 hours during the first 24 hours and on the fourth postoperative day. Results The use of rescue opioid was low in both groups, the median (range) consumption of oxycodone being 10 (0–50) mg on the day of surgery (no difference between the groups, P=0.31) and 0 (0–35) mg thereafter. The total combined consumption was 10 (0–105) mg in the fentanyl group and 20 (0–70) mg in the placebo group (P=0.23). There were no statistically significant differences in pain scores or adverse effects between the groups. Conclusion As a part of multimodal analgesia with ibuprofen and acetaminophen, a patch delivering fentanyl 12 μg/hour did not significantly decrease the consumption of rescue opioid or pain scores after forefoot surgery. PMID:25653553

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

    PubMed Central

    2012-01-01

    Background Many effective treatments for nicotine addiction inhibit noradrenaline reuptake. Three recent studies have suggested that another noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors. Methods The present double-blind, placebo-controlled, fixed-dose study was carried out over 21 days during which administration of 40 mg atomoxetine was compared to placebo in 17 individuals. Of these, nine were randomized to atomoxetine and eight to placebo. Baseline and weekly measurements were made using the Cigarette Dependence Scale (CDS), Cigarette Withdrawal Scale (CWS), Questionnaire of Smoking Urges (QSU), reported number of cigarettes smoked, and salivary cotinine levels. Results The study results showed that all those on placebo completed the study. In marked contrast, of the nine individuals who started on atomoxetine, five dropped out due to side effects. In a completer analysis there were statistically significant differences at 14 and 21 days in several measures between the atomoxetine and placebo groups, including CDS, CWS, QSU, number of cigarettes smoked (decreasing to less than two per day in the treatment group who completed the study), and a trend towards lower mean salivary cotinine levels. However, these differences were not seen in a last observation carried forward (LOCF) analysis. Conclusions In summary, this is the first study to examine the use of atomoxetine in non-psychiatric adult smokers for a period of more than 7 days, and the findings suggest that atomoxetine might be a useful treatment for nicotine addiction. However, the dose used in the current study was too high to be tolerated by many adults, and a dose-finding study is required to determine the most appropriate dose for future studies of this potential treatment for smoking cessation. PMID:22405499

  14. Effects of Lornoxicam on Anastomotic Healing: A Randomized, Blinded, Placebo-Control Experimental Study.

    PubMed

    Drakopoulou, Stamatoula; Kontis, Elissaios; Pantiora, Eirini; Vezakis, Antonios; Karandrea, Despoina; Aravidou, Eftychia; Konti-Paphiti, Agathi; Argyra, Erifili; Voros, Dionisios; Polydorou, Andreas A; Fragulidis, Georgios P

    2016-01-01

    Introduction and Aim. With the implementation of multimodal analgesia regimens, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are often administered for optimal pain control and reduction of opioid use. The aim of the study was to examine the effects of lornoxicam, a NSAID, on anastomotic healing employing an animal model. Materials and Methods. A total of 28 Wistar rats were randomly assigned in two groups. All animals underwent ascending colonic transection followed by an end-to-end hand sewn anastomosis. Group 1 received intraperitoneally lornoxicam before and daily after surgery. Group 2 received intraperitoneally an equal volume of placebo. Half of the animals in each group were euthanized on the 3rd pod and the remaining on the 7th pod. Macro- and microscopic indicators of anastomotic healing were compared using a two-tailed Fisher exact test. Results. The lornoxicam group significantly decreased fibroblast in growth and reepithelization of the mucosa at the anastomotic site on the 3rd pod and significantly increased occurrence of deep reaching defects, necrosis, and microabscess on the 7th pod. Conclusion. Lornoxicam administration during the perioperative period adversely affects histologic parameters of intestinal anastomotic healing. These effects of lornoxicam administration were not found to induce significant increase of anastomotic dehiscence in the rat model. PMID:27144224

  15. Effects of Lornoxicam on Anastomotic Healing: A Randomized, Blinded, Placebo-Control Experimental Study

    PubMed Central

    Drakopoulou, Stamatoula; Vezakis, Antonios; Karandrea, Despoina; Aravidou, Eftychia; Konti-Paphiti, Agathi; Argyra, Erifili; Voros, Dionisios

    2016-01-01

    Introduction and Aim. With the implementation of multimodal analgesia regimens, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are often administered for optimal pain control and reduction of opioid use. The aim of the study was to examine the effects of lornoxicam, a NSAID, on anastomotic healing employing an animal model. Materials and Methods. A total of 28 Wistar rats were randomly assigned in two groups. All animals underwent ascending colonic transection followed by an end-to-end hand sewn anastomosis. Group 1 received intraperitoneally lornoxicam before and daily after surgery. Group 2 received intraperitoneally an equal volume of placebo. Half of the animals in each group were euthanized on the 3rd pod and the remaining on the 7th pod. Macro- and microscopic indicators of anastomotic healing were compared using a two-tailed Fisher exact test. Results. The lornoxicam group significantly decreased fibroblast in growth and reepithelization of the mucosa at the anastomotic site on the 3rd pod and significantly increased occurrence of deep reaching defects, necrosis, and microabscess on the 7th pod. Conclusion. Lornoxicam administration during the perioperative period adversely affects histologic parameters of intestinal anastomotic healing. These effects of lornoxicam administration were not found to induce significant increase of anastomotic dehiscence in the rat model. PMID:27144224

  16. Treatment of croup with nebulised steroid (budesonide): a double blind, placebo controlled study.

    PubMed Central

    Husby, S; Agertoft, L; Mortensen, S; Pedersen, S

    1993-01-01

    The aim of this prospective, randomised, double blind study was to evaluate whether nebulised local steroid treatment is effective in the treatment of croup. Thirty six infants and children (0.4-4.9 years of age) admitted to hospital with moderate to severe croup were allocated to receive either 2 mg nebulised budesonide (20 children) or saline (16 children). Disease severity was assessed by a clinical total croup score based on stridor, cough, retractions, dyspnoea, and cyanosis. In addition the overall clinical impression was evaluated (0-100). Two hours after treatment there was a significant improvement in the total croup score in the group treated with budesonide (8 to 4.5), but not in the group treated with saline (8 to 8). Furthermore, the overall clinical impression assessment score decreased significantly (50 to 25) in the group treated with budesonide, whereas it remained constant in the placebo group (60 to 62). The total croup score and overall clinical severity were significantly better in the group treated with budesonide than in the placebo group. No side effects were observed. The results indicate that nebulised budesonide can be used as a safe and effective alternative treatment in children and infants with moderate to severe croup. PMID:8466237

  17. 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

  18. Immunologic effects of mistletoe lectins: a placebo-controlled study in healthy subjects.

    PubMed

    Huber, Roman; Rostock, Matthias; Goedl, Roland; Lüdtke, Rainer; Urech, Konrad; Klein, Reinhild

    2006-01-01

    The subcutaneous application of lectin-rich mistletoe preparations such as Iscador Quercus (IQ; Weleda Company, Schwäbisch Gmünd, Germany) results in a peripheral eosinophilia. Our goal was to investigate whether this effect is related to mistletoe lectin (ML) and whether it is caused by a response of the specific immune system. In a double-blinded study, 43 volunteers were randomized to one of four treatment groups: (1) IQ, (2) ML that was derived from IQ, (3) IQ that was depleted of ML, and (4) placebo. The respective preparations were applied subcutaneously twice per week for 8 weeks, in increasing doses. Weekly the differential blood count was analyzed. Every 4 weeks interferon-gamma, interleukin-5 (IL-5), and granulocyte-macrophage colony stimulating factor (GM-CSF) were determined in cultures from peripheral mononuclear cells after stimulation with IQ. IQ and ML resulted in significant eosinophilia compared with placebo and ML-depleted IQ. Furthermore, the leukocyte and granulocyte counts were increased in the IQ and ML groups compared with placebo. GM-CSF, interferon-gamma, and IL-5 increased after ex vivo in vitro stimulation with IQ in the IQ and ML groups, and were significantly different from placebo in the IQ group but not in the ML group. Eosinophilia during therapy with mistletoe preparations is due to its content of ML. This effect might be related to a stimulation of IL-5 and/or GM-CSF, which was demonstrated ex vivo in vitro. ML resulted in a temporary increase of the granulocyte count, which is probably related to an acute-phase reaction. PMID:16737665

  19. Interferon β-1a in ulcerative colitis: a placebo controlled, randomised, dose escalating study

    PubMed Central

    Nikolaus, S; Rutgeerts, P; Fedorak, R; Steinhart, A H; Wild, G E; Theuer, D; Möhrle, J; Schreiber, S

    2003-01-01

    Background and aims: Administration of interferon (IFN)-β may represent a rational approach to the treatment of ulcerative colitis through its immunomodulatory and anti-inflammatory effects. The present study was performed to evaluate the efficacy and tolerability of IFN-β-1a. Methods: Patients (n=18) with moderately active ulcerative colitis were randomised to receive IFN-β-1a or placebo. IFN-β-1a was started at a dose of 22 μg three times a week subcutaneously, and the dose was increased at two week intervals to 44 μg and then to 88 μg if no response was observed. The maximum duration of treatment was eight weeks. End points were clinical treatment response, defined as a decrease of at least 3 points from baseline in the ulcerative colitis scoring system (UCSS) symptoms score and induction of endoscopically confirmed remission. Results: Baseline characteristics and disease severity were similar in both groups. Data from 17 patients are included in this report (10 patients in the IFN-β-1a group and seven patients in the placebo group). Clinical response was achieved in five patients (50%) in the IFN-β-1a group and in one (14%) in the placebo group (P=0.14). Remission was achieved in three patients in the IFN-β-1a group and in none in the placebo group (p=0.02). Most adverse reactions associated with IFN-β-1a were influenza-like symptoms or injection site reactions, and were mild or moderate in severity. Conclusions: IFN-β-1a may represent a promising novel treatment approach in ulcerative colitis. PMID:12912859

  20. 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

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

    PubMed Central

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

    2015-01-01

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

  2. Midodrine in patients with spinal cord injury and anejaculation: A double-blind randomized placebo-controlled pilot study

    PubMed Central

    Leduc, Bernard E.; Fournier, Christine; Jacquemin, Géraldine; Lepage, Yves; Vinet, Bernard; Hétu, Pierre-Olivier; Chagnon, Miguel

    2015-01-01

    Objective The objective of this study is to evaluate the efficacy of midodrine in the treatment of anejaculation in men with spinal cord injury (SCI). Study design Prospective, double-blind, randomized, placebo-controlled pilot study. Method Men with anejaculation associated with SCI (level of injury above T10) of more than 1 year in duration were approached. Those with no ejaculatory response to one penile vibratory stimulation (PVS) trial were assigned in a double-blind manner to one of the two following interventions once a week for a maximum of 3 weeks or until ejaculation occurred: oral administration of flexible midodrine (7.5–22.5 mg max) followed by PVS (group M), or oral administration of flexible sham-midodrine (placebo) followed by PVS (group P). Sociodemographic data, medical characteristics, and plasma desglymidodrine concentration were collected for all participants. Outcome measure Ejaculation success rate in each group. Results Among the 78 men approached, 23 participants (level of SCI: C4–T9) were randomized. Three participants abandoned the study and 20 completed the study; 10 were assigned to group M, 10 to group P. Ejaculation was reached for one participant of group M and for two participants of group P. Autonomic dysreflexia associated to PVS occurred in three patients. Conclusion In this small sample study, treatment of anejaculation after SCI with midodrine and PVS did not result in a better rate of antegrade ejaculation in 10 men than in 10 men treated with a placebo and PVS. PMID:24969635

  3. Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study

    PubMed Central

    Kawahara, Tetsuya; Suzuki, Gen; Inazu, Tetsuya; Mizuno, Shoichi; Kasagi, Fumiyoshi; Okada, Yosuke; Tanaka, Yoshiya

    2016-01-01

    Introduction Recent research suggests that vitamin D deficiency may cause both bone diseases and a range of non-skeletal diseases. However, most of these data come from observational studies, and clinical trial data on the effects of vitamin D supplementation on individuals with pre-diabetes are scarce and inconsistent. The aim of the Diabetes Prevention with active Vitamin D (DPVD) study is to assess the effect of eldecalcitol, active vitamin D analogue, on the incidence of type 2 diabetes among individuals with pre-diabetes. Methods and analysis DPVD is an ongoing, prospective, multicentre, randomised, double-blind and placebo-controlled outcome study in individuals with impaired glucose tolerance. Participants, men and women aged ≥30 years, will be randomised to receive eldecalcitol or placebo. They will also be given a brief (5–10 min long) talk about appropriate calorie intake from diet and exercise at each 12-week visit. The primary end point is the cumulative incidence of type 2 diabetes. Secondary endpoint is the number of participants who achieve normoglycaemia at 48, 96 and 144 weeks. Follow-up is estimated to span 144 weeks. Ethics and dissemination All protocols and an informed consent form comply with the Ethics Guideline for Clinical Research (Japan Ministry of Health, Labour and Welfare). The study protocol has been approved by the Institutional Review Board at Kokura Medical Association and University of Occupational and Environmental Health. The study will be implemented in line with the CONSORT statement. Trial registration number UMIN000010758; Pre-results. PMID:27388357

  4. A natural seaweed derived mineral supplement (Aquamin F) for knee osteoarthritis: A randomised, placebo controlled pilot study

    PubMed Central

    Frestedt, Joy L; Kuskowski, Michael A; Zenk, John L

    2009-01-01

    Background Osteoarthritis (OA) is a slowly destructive process that may be influenced by a nutritional mineral balance in the body. Methods This small, double blind, placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin) on 6 minute walking distance (6 MWD), range of motion (ROM), and pain and joint mobility measured by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs (NSAIDs) that were being used daily for pain management. Subjects (n = 29) with moderate to severe OA of the knee were randomised to receive either Aquamin (2400 mg/d) or Placebo for up to 12 weeks. Results Of the 29 subjects initially randomized, only 22 subjects proceeded to treatment due to 7 subjects not meeting study selection criteria at baseline. Fourteen subjects completed the study and an ITT analysis (n = 22) of the data showed no significant differences in WOMAC scores however, the data did reveal significant improvements in passive and active extension ROM (0.83° ± 1.54 vs. -1.54° ± 2.43; difference, 5.2° ± 2.2, p = 0.028) and 6 MWD (150 ± 48 ft vs. 12.5 ± 31.5 ft; difference, 136 ± 57 ft, p = 0.03) in the Aquamin group compared to the placebo group; respectively, following a 50% reduction in NSAID use. The treatments were well tolerated and the adverse event profiles were not significantly different between the groups. Conclusion This small preliminary study suggests Aquamin may increase range of motion and walking distances in subjects with OA of the knee and may allow partial withdrawal of NSAIDs over 12 weeks of treatment. Additional research is needed to confirm these preliminary observations. Trial registration NCT00755482 PMID:19187557

  5. Single dose efficacy evaluation of two partial benzodiazepine receptor agonists in photosensitive epilepsy patients: A placebo-controlled pilot study.

    PubMed

    Kasteleijn-Nolst Trenité, Dorothée G A; Groenwold, Rolf H H; Schmidt, Bernd; Löscher, Wolfgang

    2016-05-01

    Benzodiazepines (BZDs) are highly effective to suppress various types of seizures; however, their clinical use is limited due to adverse effects and tolerance and dependence liability. Drugs that act only as partial agonists at the BZD recognition site (initially termed "BZD receptor") of the GABAA receptor chloride ionophore complex or exhibit a GABAA receptor subtype-selectivity are thought to have advantages vs. full agonists such as diazepam and most other clinically used BZDs in that such compounds have less adverse effects and reduced or absent tolerance and dependence liability. One of such compounds, abecarnil, has been clinically evaluated as a novel anxiolytic drug, but, despite its potent preclinical anti-seizure activity, it has not yet been evaluated in patients with epilepsy. In the present proof-of-concept study, we performed a within-subject placebo-controlled, single oral dose study of abecarnil in patients with photosensitive epilepsy. Flumazenil, which is generally considered a BZD receptor antagonist, but has slight partial agonistic properties, was used for comparison. In total, 12 patients were enrolled in this study. Abecarnil, 5 or 10mg, completely abolished the photo-paroxysmal EEG response, while flumazenil, 30, 60 or 100mg, was less effective. The anti-epileptic effect of abecarnil was significantly different from both placebo and flumazenil. Sedative adverse effects were observed after abecarnil but not flumazenil. The study substantiates previous pre-clinical experiments that abecarnil exerts pronounced anti-seizure activity. Epilepsy is often associated with anxiety, so that the anxiolytic activity of abecarnil would be an added advantage when using this compound in epilepsy patients. PMID:26921854

  6. Efficacy of a novel chitosan formulation on fecal fat excretion: a double-blind, crossover, placebo-controlled study.

    PubMed

    Barroso Aranda, Jorge; Contreras, Francisco; Bagchi, Debasis; Preuss, Harry G

    2002-01-01

    The ability of a novel chitosan formulation to influence gastrointestinal fat absorption in vivo was examined in a double-blind, placebo-controlled, crossover study by determining the content of total fat in feces in two groups of subjects. Twenty-nine normal healthy subjects were recruited for the study. Twenty-four participants completed the test period with the chitosan formulation, and 21 completed the placebo phase of study. During the placebo and the test periods, the subjects were administered six capsules three times daily 10 minutes before meals for three days and for the two days of the stool collection. A daily serving of six tablets of the test compound contained 2100 mg chitosan and 300 mg psyllium husk seeds. In respect to the baseline period, the test compound increased fat excretion significantly whether the test period preceded or proceeded the placebo period (p<0.02 and p<0.05 respectively). In contrast, essentially no changes were seen during the placebo loading periods. Compared to the difference between placebo period and its baseline period, a statistically significant increase in fecal fat excretion was observed over baseline following oral supplementation of a novel formulation of chitosan and psyllium husk seeds [+3.63 gm/day +/- 0.83 (SEM) vs. -0.15 gm/day +/- 0.94 (SEM) (p=0.004)]. The average daily increase in fecal fat of 3-4 grams over control could account for a decrease in calorie consumption of 30-40 kcal per day. A total of 19 subjects completed both parts of the study. Examining the data from these 19 subjects by ANOVA, it was found that the period when the test compounds were given was statistically significantly different from the placebo baseline, placebo experimental, and test baseline periods. Using multiple comparisons, it was ascertained that the novel formulation containing chitosan plus psyllium husk seeds increases fecal fat excretion. PMID:12939120

  7. Effects of phylloquinone supplementation on lipid profile in women with rheumatoid arthritis: a double blind placebo controlled study

    PubMed Central

    Kolahi, Sousan; Pourghassem Gargari, Bahram; Mesgari Abbasi, Mehran; Asghari Jafarabadi, Mohammad

    2015-01-01

    BACKGROUND/OBJECTIVES Rheumatoid arthritis (RA) is associated with an excess mortality from cardiovascular disease which is likely attributed to an atherogenic lipid profile. Among nutritional factors vitamin K has been recently focused as a pivotal nutrient in improvement of lipid related markers. Thus, this study was designed to determine the effects of vitamin K on lipid profile in this disease. SUBJECTS/METHODS Fifty eight patients with definitive RA were participated in the present double blind placebo controlled study. They were randomly allocated into two groups to receive vitamin K1 as phylloquinone [10 mg/day] (n = 30) or placebo pills (n = 28), for eight weeks. In order to control the effects of probable confounders dietary intakes, anthropometric measurements including weight and height, clinical status using disease activity score-28 (DAS-28), physical activity and anxiety status were evaluated at baseline. Moreover, serum levels of lipid related markers including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were measured at baseline and at the end of intervention. RESULTS There were no significant differences between the two groups regarding any of the baseline characteristics. After adjusting for some relevant confounders, in comparison between two groups, we observed no significant changes in lipid related markers at the end of intervention. Also, there was no significant difference between before and after intervention values within groups (P > 0.05). CONCLUSIONS Function of vitamin K1 in lipid profile modification remains still controversial. This study showed that vitamin K1 has no effect on lipid profile in women with rheumatoid arthritis. Further studies with a longer follow-up are required to determine the effects of vitamin K on atherogenic lipid profile. PMID:25861426

  8. 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

  9. 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. PMID:26428734

  10. Effects of PEMF on patients with osteoarthritis: Results of a prospective, placebo-controlled, double-blind study.

    PubMed

    Wuschech, Heinz; von Hehn, Ulrike; Mikus, Eberhard; Funk, Richard H

    2015-12-01

    This study aimed to evaluate effects of pulsed electromagnetic fields (PEMF) in a double blind study on patients with knee joint osteoarthritis. The MAGCELL ARTHRO electrode-less therapy delivered a sinusoidal magnetic field, varying in frequency between 4 and 12 Hz. In 1 cm tissue depth, magnetic flux density was 105 mT. A total of n = 57 patients were randomly assigned to the verum, PEMF or placebo group (placebo device). Their average age was 61.6 ± 12.0 years. According to American College of Rheumatology criteria the osteoarthritis level was 2.8 ± 0.8. Treatment was performed twice a day for 5 min over a period of 18 days. Treatment with the MAGCELL device versus control (sham exposed) showed a highly significant reduction in pain (P < 0.001), a significant reduction in stiffness (P = 0.032) and a significant reduction in disability in daily activities (P = 0.005) according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scales-with a good overall treatment tolerance. In the placebo group there was no evidence of a significant change between the initial and final examination in any of the three above-mentioned WOMAC scales. Results of this partly randomized placebo-controlled double-blind study show clinically at any rate, that use of PEMF lead to highly significant better results in the treatment group compared to the placebo group with regard to the total WOMAC global score and especially for visual analogue scale. Patient assessment of the "effectiveness" was rated in 29.5% as very good and good in 27.3% compared to 0.0% and 15.4% in controls. This therapy is thus a useful complementary treatment option with no side effects. PMID:26562074

  11. Effects of American ginseng (Panax quinquefolius) on neurocognitive function: an acute, randomised, double-blind, placebo-controlled, crossover study

    PubMed Central

    Ossoukhova, Anastasia; Owen, Lauren; Ibarra, Alvin; Pipingas, Andrew; He, Kan; Roller, Marc; Stough, Con

    2010-01-01

    Rationale Over the last decade, Asian ginseng (Panax ginseng) has been shown to improve aspects of human cognitive function. American ginseng (Panax quinquefolius) has a distinct ginsenoside profile from P. ginseng, promising cognitive enhancing properties in preclinical studies and benefits processes linked to human cognition. Objectives The availability of a highly standardised extract of P. quinquefolius (Cereboost™) led us to evaluate its neurocognitive properties in humans for the first time. Methods This randomised, double-blind, placebo-controlled, crossover trial (N = 32, healthy young adults) assessed the acute mood, neurocognitive and glycaemic effects of three doses (100, 200 400 mg) of Cereboost™ (P. quinquefolius standardised to 10.65% ginsenosides). Participants' mood, cognitive function and blood glucose were measured 1, 3 and 6 h following administration. Results There was a significant improvement of working memory (WM) performance associated with P. quinquefolius. Corsi block performance was improved by all doses at all testing times. There were differential effects of all doses on other WM tasks which were maintained across the testing day. Choice reaction time accuracy and ‘calmness’ were significantly improved by 100 mg. There were no changes in blood glucose levels. Conclusions This preliminary study has identified robust working memory enhancement following administration of American ginseng. These effects are distinct from those of Asian ginseng and suggest that psychopharmacological properties depend critically on ginsenoside profiles. These results have ramifications for the psychopharmacology of herbal extracts and merit further study using different dosing regimens and in populations where cognition is fragile. PMID:20676609

  12. Preoperative pain treatment in acute abdomen in Osogbo, Nigeria: a randomized double-blind placebo-controlled study

    PubMed Central

    2013-01-01

    Background Withholding analgesics in acute abdomen for fear of masking clinical features and impairing diagnosis and decision-making is still being practiced despite recent evidence to the contrary. This study assesses the effect of preoperative analgesia on clinical findings, clinical diagnosis, and decision-making in patients with non-trauma acute abdomen. Method This is a randomized, double-blind, placebo-controlled study using Tramal, a brand of tramadol, at the ED of LAUTECH Teaching Hospital Osogbo, Nigeria. Ninety-five patients between 18–60 years received Tramal (n = 46) or placebo (n = 49). The pain score, clinical findings, provisional diagnosis, and treatment plan were noted before and 15–20 min after administration of the analgesic or placebo. The final diagnosis arrived at after adequate investigation or operation was considered the gold standard. The pain scores, diagnosis, treatment plan, and decision between the two groups were compared. Statistical analysis was by SPSS 16. Results were considered statistically significant at p < 0.05. Results Demography and case distribution were similar in both groups. The improvement in pain was greater in the Tramal group (p = 0.001). The abdominal palpation findings were also better in the Tramal group (p = 0.02). There were more changes in the diagnosis after use of Tramal (p = 0.01). There were more changes in the decision in the Tramal group (p = 0.03). Most of the changes in diagnosis and decision in the Tramal group were for the better. Conclusion The preoperative use of Tramal in acute abdomen improved the experience of pain and did not adversely affect the accuracy of the diagnosis or decision-making. PMID:23343476

  13. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Sun, Qianqian; Wang, Bin; Li, Yingsha; Sun, Fang; Li, Peng; Xia, Weijie; Zhou, Xunmei; Li, Qiang; Wang, Xiaojing; Chen, Jing; Zeng, Xiangru; Zhao, Zhigang; He, Hongbo; Liu, Daoyan; Zhu, Zhiming

    2016-03-01

    Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function. PMID:26781281

  14. 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

  15. Sildenafil citrate as a medical expulsive therapy for distal ureteric stones: A randomised double-blind placebo-controlled study

    PubMed Central

    Shokeir, Ahmed A.; Tharwat, Mohamed A.; Abolazm, Ahmed Elhussein; Harraz, Ahmed

    2016-01-01

    Objective To study the effect of sildenafil citrate on spontaneous passage of distal ureteric stones (DUS). Patients and methods This was a randomised double-blinded placebo-controlled study of 100 patients with DUS. Inclusion criteria were: male, age 18–65 years, normal renal function, and a single radiopaque unilateral DUS of 5–10 mm. Patients were randomly allocated into two equal groups, one that received placebo and the other that received 50 mg sildenafil citrate once daily. Both investigators and patients were masked to the type of treatment. Patients self-administered the medication until spontaneous passage of the DUS. In patients where there was uncontrolled pain, fever, an increase in serum creatinine of >1.8 mg/dL, progressive hydronephrosis or no further progress after 4 weeks, a decision was taken for further treatment. Results In all, 47 and 49 patients were available for analysis in both the placebo and sildenafil citrate groups; respectively. Both groups were comparable for age and stone characteristics. Spontaneous expulsion occurred in 19 of 47 patients (40.4%) in the placebo group and in 33 of 49 (67.3%) in the sildenafil citrate group (P = 0.014). The mean time to stone expulsion was significantly shorter in the sildenafil citrate group (P < 0.001). A multivariable Cox proportional hazards model showed that receiving sildenafil citrate was the only independent factor that had a significant impact on stone passage with a hazard ratio of 2.7 (95% confidence interval 1.5–4.8; P < 0.001). Conclusion Sildenafil citrate enhances spontaneous passage of 5–10 mm DUS. PMID:26966585

  16. 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. PMID:25931419

  17. Varenicline and Nicotine Patch Therapies in Young Adults Motivated to Quit Smoking: A Randomized, Placebo-controlled, Prospective Study.

    PubMed

    Tuisku, Anna; Salmela, Merita; Nieminen, Pentti; Toljamo, Tuula

    2016-07-01

    This study compares the nicotine patch to placebo in young adult light smokers, and the nicotine patch to varenicline in heavy smokers. Volunteer daily smokers were recruited into a randomized, placebo-controlled study via community media, colleges and the army (aged 18-26 years). Those subjects with light tobacco dependence were randomized to (i) placebo patch (n = 86) and (ii) nicotine patch 10 mg/16 hr for 8 weeks (n = 94), and those with stronger dependence to (iii) nicotine patch 15 mg/16 hr for 8 weeks (n = 51) and (iv) varenicline for 12 weeks (n = 60). The primary outcome variable was self-reported smoking abstinence at week 12. Secondary outcome variables were self-reported smoking abstinence at weeks 4 and 26, and self-reported abstinence verified by saliva cotinine level at week 12. The prevalence of self-reported smoking abstinence did not differ statistically significantly in light smokers during the follow-up (week 4: 19.8% for placebo patch and 26.6% for nicotine patch 10 mg/16 hr; week 12: 17.4% versus 23.4%; week 26: 15.1% versus 20.2%), but the groups of heavy smokers differed significantly for 12 weeks (week 4: 19.6% for nicotine patch 15 mg/16 hr and 73.3% for varenicline, p < 0.001; week 12: 15.7% versus 36.7%, p = 0.018). This statistically significant difference did not endure for the entire follow-up (week 26: 9.8% versus 18.3%, p = 0.280). However, saliva cotinine verified abstinence at week 12 did not support self-reported abstinence. Varenicline may be more effective than the nicotine patch as a smoking cessation pharmacotherapy among young adult heavy smokers in the short-term. PMID:26709238

  18. Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

    PubMed

    Melehan, K L; Hoyos, C M; Yee, B J; Wong, K K; Buchanan, P R; Grunstein, R R; Liu, P Y

    2016-01-01

    Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing. PMID:26610430

  19. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study.

    PubMed

    Brautigam, M R; Blommaert, F A; Verleye, G; Castermans, J; Jansen Steur, E N; Kleijnen, J

    1998-12-01

    A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters. After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29). In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups. These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising

  20. Short-term effects of inhaled salbutamol on autonomic cardiovascular control in healthy subjects: a placebo-controlled study

    PubMed Central

    Cekici, Leyla; Valipour, Arschang; Kohansal, Robab; Burghuber, Otto Chris

    2009-01-01

    AIMS To investigate short-term effects of inhaled salbutamol on haemodynamic changes and cardiovascular autonomic control. METHODS A randomized, single-blinded, placebo-controlled study of 0.2 mg of inhaled salbutamol was conducted on 12 healthy nonsmoking volunteers with a mean age of 24 ± 2 years at two different testing sessions. Non-invasively obtained continuous haemodynamic measurements of cardiac output, beat-to-beat arterial blood pressure, and total peripheral resistance were recorded prior to and for a total of 120 min after inhalation of the respective study drug. Continuous cardiovascular autonomic tone was recorded using power spectral analysis of heart rate and blood pressure variability. Spontaneous baroreceptor activity was assessed by the sequence method. RESULTS There were no significant changes in any of the baseline parameters between the different testing sessions. Inhalation of salbutamol caused a significant increase in cardiac output from 6.7 ± 1.3 to 7.7 ± 1.4 l min−1 (P < 0.05), and a decrease in total peripheral resistance from 1076 ± 192 to 905 ± 172 dyne s−1 cm−5 (P < 0.05) within 15 min after inhalation. Moreover, salbutamol significantly increased sympathetically mediated low-frequency heart rate variability (P < 0.01), whereas parasympathetically mediated high-frequency heart rate variability decreased (P < 0.01). All changes persisted for approximately 30 min and were fully reversible at 120 min. There were no significant changes in systolic blood pressure variability or spontaneous baroreceptor activity. CONCLUSIONS Inhalation of therapeutic doses of salbutamol in healthy subjects resulted in significant haemodynamic changes and a shift of sympathovagal balance towards increased sympathetic tone in the absence of baroreceptor activation. PMID:19371312

  1. Adductor Canal Block for Postoperative Pain Treatment after Revision Knee Arthroplasty: A Blinded, Randomized, Placebo-Controlled Study

    PubMed Central

    Jæger, Pia; Koscielniak-Nielsen, Zbigniew J.; Schrøder, Henrik M.; Mathiesen, Ole; Henningsen, Maria H.; Lund, Jørgen; Jenstrup, Morten T.; Dahl, Jørgen B.

    2014-01-01

    Background Revision knee arthroplasty is assumed to be even more painful than primary knee arthroplasty and predominantly performed in chronic pain patients, which challenges postoperative pain treatment. We hypothesized that the adductor canal block, effective for pain relief after primary total knee arthroplasty, may reduce pain during knee flexion (primary endpoint: at 4 h) compared with placebo after revision total knee arthroplasty. Secondary endpoints were pain at rest, morphine consumption and morphine-related side effects. Methods We included patients scheduled for revision knee arthroplasty in general anesthesia into this blinded, placebo-controlled, randomized trial. Patients were allocated to an adductor canal block via a catheter with either ropivacaine or placebo; bolus of 0.75% ropivacaine/saline, followed by infusion of 0.2% ropivacaine/saline. Clinicaltrials.gov ID: NCT01191593. Results We enrolled 36 patients, of which 30 were analyzed. Mean pain scores during knee flexion at 4 h (primary endpoint) were: 52±22 versus 71±25 mm (mean difference 19, 95% CI: 1 to 37, P = 0.04), ropivacaine and placebo group respectively. When calculated as area under the curve (1–8 h/7 h) pain scores were 55±21 versus 69±21 mm during knee flexion (P = 0.11) and 39±18 versus 45±23 mm at rest (P = 0.43), ropivacaine and placebo group respectively. Groups were similar regarding morphine consumption and morphine-related side effects (P>0.05). Conclusions The only statistically significant difference found between groups was in the primary endpoint: pain during knee flexion at 4 h. However, due to a larger than anticipated dropout rate and heterogeneous study population, the study was underpowered. Trial Registration Clinicaltrials.gov NCT01191593 PMID:25386752

  2. Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial—study protocol

    PubMed Central

    Diem, Ricarda; Molnar, Fanni; Beisse, Flemming; Gross, Nikolai; Drüschler, Katharina; Heinrich, Sven P; Joachimsen, Lutz; Rauer, Sebastian; Pielen, Amelie; Sühs, Kurt-Wolfram; Linker, Ralf Andreas; Huchzermeyer, Cord; Albrecht, Philipp; Hassenstein, Andrea; Aktas, Orhan; Guthoff, Tanja; Tonagel, Felix; Kernstock, Christoph; Hartmann, Kathrin; Kümpfel, Tania; Hein, Katharina; van Oterendorp, Christian; Grotejohann, Birgit; Ihorst, Gabriele; Maurer, Julia; Müller, Matthias; Volkmann, Martin; Wildemann, Brigitte; Platten, Michael; Wick, Wolfgang; Heesen, Christoph; Schiefer, Ulrich; Wolf, Sebastian; Lagrèze, Wolf A

    2016-01-01

    Introduction Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. Methods and analysis Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. Ethics and dissemination TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki

  3. Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study

    PubMed Central

    Tuomainen, Tomi-Pekka; Virtanen, Jyrki K.; Voutilainen, Sari; Nurmi, Tarja; Mursu, Jaakko; de Mello, Vanessa D. F.; Schwab, Ursula; Hakumäki, Martti; Pulkki, Kari

    2015-01-01

    Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 μg/d, or 80 μg/d vitamin D3) was carried out among sixty-eight overweight (BMI 25–35) and aging (≥60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and either impaired fasting glucose or impaired glucose tolerance. Analyses included 66 subjects who completed the trial. Glucose metabolism was evaluated by fasting and 2-hour oral glucose tolerance test-derived indices and glycated hemoglobin. Inflammation was evaluated by high-sensitive C-reactive protein and five cytokines. Although a dose-dependent increase in serum 25(OH)D3 over the supplementation period was observed (P trend < 0.001), there were no other statistically significant differences in changes in the 13 glucose homeostasis indicators between the study groups other than increase in the 120 min glucose concentration (P trend = 0.021) and a decreasing trend both in 30 min plasma insulin (P trend = 0.030) and glycated hemoglobin (P trend = 0.024) concentrations. A borderline statistically significant decreasing trend in interleukin-1 receptor antagonist concentration was observed (P = 0.070). Vitamin D3 supplementation does not improve glucose metabolism in ageing subjects with prediabetes but may have modest anti-inflammatory effects. PMID:26106626

  4. 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

  5. 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.

  6. Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study

    PubMed Central

    Singh, Arvinderpal; Sharma, Geeta; Gupta, Ruchi; Kumari, Anita; Tikko, Deepika

    2016-01-01

    Background and Aims: Pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia. Tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice. However, their potential to relieve propofol injection pain still needs to be explored. Material and Methods: A randomized, double-blind, placebo-controlled study was conducted on 90 American Society of Anesthesiologists I and II adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent. Consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each. Group I patients received an injection of normal saline 3 ml intravenously (placebo) while Group II and Group III patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously, respectively. Before induction of anesthesia patients were asked about the intensity of pain on propofol injection by using visual analog scale (VAS) before the loss of consciousness. Descriptive statistics and analysis of variance with Chi-square test were used to analyze the data. The value of P < 0.05 was considered as a significant and P < 0.0001 as highly significant. Results: The incidence of pain in Group I was observed in 80% of the patients, while it was observed in 23.33% and 20% of patients in Group II and III, respectively. Mean VAS scores were 2.27 ± 1.51, 1.14 ± 1.74, and 1.03 ± 1.72 in Group I, II, and Group III patients, respectively. The incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in Group II and III, respectively. Conclusion: Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain. PMID:27006549

  7. Effect of two dietary fibers on satiety and glycemic parameters: a randomized, double-blind, placebo-controlled, exploratory study

    PubMed Central

    2014-01-01

    Background Dietary carbohydrates may affect metabolic and physiologic parameters. The present study evaluated whether a combination of two dietary fibers, oligofructose (OFS) and pectin (P), altered satiety and glycemic parameters. The primary objective of this study was to determine whether dietary supplementation for 3 weeks with OFS + P would produce a greater reduction in energy intake of an ad libitum test meal compared to control. Methods This was a single center, randomized, double-blind, placebo-controlled, parallel group study in overweight and obese, otherwise healthy, subjects (N = 96). There were two OFS + P treatment groups: high-dose (30 g/d), low-dose (15 g/d), and a control group (maltodextrin 15 g/d). Energy intake, appetite measures based on Satiety Labeled Intensity Magnitude (SLIM) scale, fasting and post-prandial glucose, and insulin levels and body weight were measured at baseline and at the end of 3 weeks. Adverse events and gastrointestinal tolerability of the treatments were also assessed. Results An analysis of covariance (ANCOVA) performed on the primary endpoint change from baseline in energy intake, showed no statistically significant difference in energy intake among the three treatment groups (p = 0.5387). The LS mean changes (SE) in energy intake from baseline to week 3 were −58.3 (42.4) kilocalories (kcal) for the high dose group, −74.2 (43.6) kcal for the low dose group, and −9.0 (42.9) kcal for the control group. For the pairwise comparisons of OFS + P doses and control, confidence intervals were constructed around the difference in LS mean changes. All study products were generally well tolerated. Conclusion There was a directional benefit in ad libitum energy intake for both OFS + P doses compared to control, with a greater reduction in kilocalories in the low dose comparison, but the reductions were not significant. Further studies are warranted. Clinical trial registration GSK Clinical Study

  8. Efficacy of brexpiprazole in patients with acute schizophrenia: Review of three randomized, double-blind, placebo-controlled studies.

    PubMed

    Correll, Christoph U; Skuban, Aleksandar; Hobart, Mary; Ouyang, John; Weiller, Emmanuelle; Weiss, Catherine; Kane, John M

    2016-07-01

    Brexpiprazole, a serotonin-dopamine activity modulator, is a partial agonist at 5-HT1A and dopamine D2 receptors, and antagonist at 5-HT2A and noradrenaline α1B and α2C receptors, all at similar potency. Efficacy of brexpiprazole was evaluated in patients with acutely exacerbated schizophrenia in three short-term, randomized, double-blind, placebo-controlled studies. In a Phase 2 study, patients were randomized to brexpiprazole 0.25mg (fixed dose), 1.0±0.5mg, 2.5±0.5mg, 5.0±1mg (flexible-dose ranges), placebo, or aripiprazole 15±5mg. In two Phase 3 studies, patients were randomized to fixed-dose brexpiprazole 0.25mg, 1mg, 2mg, or 4mg, or placebo. For this review, brexpiprazole 2mg and 4mg arms from the Phase 3 studies were combined. Primary efficacy endpoint was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline at week 6; key secondary endpoint was change in Clinical Global Impression-Severity of illness (CGI-S) score at week 6. Primary outcome moderator analyses explored effects of sex, age, race, and illness duration. There were no statistically significant differences vs. placebo in the Phase 2 brexpiprazole and aripiprazole groups for primary and key secondary endpoints. Combined brexpiprazole 2mg (n=359) and 4mg (n=359) were superior to placebo (n=358) in change in PANSS total score (least square mean difference from placebo: -5.46, p=0.0004, and -6.69, p<0.0001, respectively) and CGI-S (-0.25, p=0.0035, and -0.38, p<0.0001, respectively). Changes from baseline in efficacy endpoints were minimal in the 0.25mg group, while the 1mg group exhibited suboptimal improvement. No relevant moderators were identified. Meta-analysis of the pivotal studies indicates brexpiprazole 2mg and 4mg are effective in treating acute schizophrenia. PMID:27157799

  9. Management of toenail onychomycosis with 2% butenafine and 20% urea cream: a placebo-controlled, double-blind study.

    PubMed

    Syed, T A; Ahmadpour, O A; Ahmad, S A; Shamsi, S

    1998-10-01

    Onychomycosis is an increasingly common and recalcitrant fungal nail infection world-wide. The purpose of this placebo-controlled, double-blind study was to determine the clinical efficacy, chemical avulsion, and tolerability of 2% butenafine hydrochloride and 20% urea incorporated in a cream to cure toenail onychomycosis in a preselected population. Sixty patients (38M, 22F), ranging between 18 and 60 years (mean 27.4), with more than 25% involvement of the big toenail were enrolled in the study. The diagnosis of onychomycosis was established by mycologic identification and reconfirmed by positive fungal culture. A precoded 25-g tube was randomly assigned to each patient (50 active and 10 placebo) with instructions to apply the trial medication to their infected toenail twice daily with an occlusive dressing for one week. The affected nail was removed with a nail clipper. No occlusive dressing was maintained after the initial one week regimen. To assess the chemical avulsion of the infected toenail, mycologic cure, clinical effectiveness of the treatment, and overall success, patients were examined twice a week for 16 weeks and thereafter on a weekly basis for a further 36 weeks. The treatment was well tolerated by all the patients throughout the study, with no dropouts. Marked improvement was seen in 73.3% patients after weeks 8, 16 and 24 with clinically and mycologically confirmed negative fungal culture. Code disclosure revealed that active butenafine and urea cream cured significantly more patients than placebo (88% versus 0%; p < 0.0001). Of the 60 patients 91.6% reported no drug-related adverse symptoms. Five patients reported non-objective mild inflammation without discontinuation of the treatment. During one year follow-up of the study phase, none of the cured patients had a relapse. In conclusion, the mycologic and overall assessment of this study demonstrate that 2% butenafine HCl and 20% urea incorporated in a cream for keratinolysis is safe to use and

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

    PubMed

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

    2016-04-01

    Objective This randomized, double-blind placebo-controlled study compared the efficacy and tolerability of escitalopram (10 and 20 mg/day) in Japanese patients with social anxiety disorder (SAD). Research design and methods Patients aged 18-64 years with a primary diagnosis of DSM-IV-TR defined SAD, a Liebowitz Social Anxiety Scale Japanese version (LSAS-J) total score ≥60 and a Clinical Global Impression-Severity (CGI-S) score ≥4 at baseline were randomly assigned (1:1:1) to placebo, escitalopram 10 mg or escitalopram 20 mg. The primary endpoint was change from baseline to Week 12 in the LSAS-J total score for both escitalopram 10 mg and 20 mg versus placebo (ANCOVA, FAS, LOCF), using a hierarchical testing procedure. Pre-specified secondary endpoints included LSAS-J sensitivity analyses. Clinical trial registration This study has the www.japic.or.jp identifier: JapicCTI-121842. Results For the primary efficacy endpoint, the difference from placebo in the LSAS-J was -3.9 (p = 0.089) for escitalopram 10 mg. Since the superiority of escitalopram 10 mg over placebo was not confirmed, an analysis without multiplicity adjustment was made, which showed a difference for escitalopram 20 mg versus placebo of -9.8 (p < 0.001). In pre-specified sensitivity analyses, the difference versus placebo was -4.9 (p = 0.035) (ANCOVA, FAS, OC) and -5.0 (p = 0.028) (MMRM, FAS) (escitalopram 10 mg) and -10.1 (p < 0.001) (ANCOVA, FAS, OC) and -10.6 (p < 0.001) (MMRM, FAS) (escitalopram 20 mg). Common adverse events (incidence ≥5% and significantly different from placebo) were somnolence, nausea and ejaculation disorder. Conclusion Escitalopram was efficacious, safe and well tolerated by patients with SAD in Japan. Study limitations are discussed including patient characteristics. PMID:26808688

  11. Ziprasidone in Adolescents with Schizophrenia: Results from a Placebo-Controlled Efficacy and Long-Term Open-Extension Study

    PubMed Central

    Çavuş, Idil; Pappadopulos, Elizabeth; Vanderburg, Douglas G.; Schwartz, Jeffrey H.; Gundapaneni, Balarama K.; DelBello, Melissa P.

    2013-01-01

    Abstract Objective The purpose of this study was to evaluate the short- and long-term efficacy, safety, and tolerability of ziprasidone in adolescents with schizophrenia. Methods Subjects ages 13–17 years with schizophrenia (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM-IV]) were enrolled in a 6 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized in a 2:1 ratio to flexible-dose oral ziprasidone (40–160 mg/day, based on weight) or placebo. Primary end-point was change from baseline in Brief Psychiatric Rating Scale–Anchored (BPRS-A) total score. Safety assessments included adverse events, vital signs, laboratory measures, electrocardiograms, weight and body mass index, and movement disorder ratings. Results Planned interim analysis for the primary end-point in the RCT resulted in early termination of both studies because of futility. In the RCT, 283 subjects received ziprasidone (n=193) or placebo (n=90). In the intent-to-treat analysis population, the least squares mean (SE) BPRS–A score decrease from baseline at week 6 was not significantly different (p=0.15; −14.16 [0.78] for ziprasidone and −12.35 [1.05] for placebo). Per-protocol analysis was significant (p=0.02). In the OLE, 221 subjects entered the OLE and received ziprasidone for a median of 99 days. The mean (SD) change in BPRS-A score from end of RCT to end of OLE (last observation carried forward) was −6.9 (8.9). The most common treatment-emergent adverse events (≥10%) for all causalities during the RCT were somnolence and extrapyramidal disorders, and during OLE was somnolence only. No subjects had Fridericia's corrected QT (QTcF) ≥500 ms in the RCT or OLE phases. One completed suicide occurred during the OLE phase. For RCT and OLE, no clinically significant changes were reported in metabolic indices and laboratory measures

  12. Homeopathy for Depression: A Randomized, Partially Double-Blind, Placebo-Controlled, Four-Armed Study (DEP-HOM)

    PubMed Central

    Adler, Ubiratan C.; Krüger, Stephanie; Teut, Michael; Lüdtke, Rainer; Schützler, Lena; Martins, Friederike; Willich, Stefan N.; Linde, Klaus; Witt, Claudia M.

    2013-01-01

    Background The specific clinical benefit of the homeopathic consultation and of homeopathic remedies in patients with depression has not yet been investigated. Aims To investigate the 1) specific effect of individualized homeopathic Q-potencies compared to placebo and 2) the effect of an extensive homeopathic case taking (case history I) compared to a shorter, rather conventional one (case history II) in the treatment of acute major depression (moderate episode) after six weeks. Methods A randomized, partially double-blind, placebo-controlled, four-armed trial using a 2×2 factorial design with a six-week study duration per patient was performed. Results A total of 44 from 228 planned patients were randomized (2∶1∶2∶1 randomization: 16 homeopathic Q-potencies/case history I, 7 placebo/case history I, 14 homeopathic Q-potencies/case history II, 7 placebo/case history II). Because of recruitment problems, the study was terminated prior to full recruitment, and was underpowered for the preplanned confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous and inconclusive results with large variance in the sample. The mean difference for the Hamilton-D after 6 weeks was 2.0 (95%CI −1.2;5.2) for Q-potencies vs. placebo and −3.1 (−5.9;−0.2) for case history I vs. case history II. Overall, no consistent or clinically relevant results across all outcomes between homeopathic Q-potencies versus placebo and homeopathic versus conventional case taking were observed. The frequency of adverse events was comparable for all groups. Conclusions Although our results are inconclusive, given that recruitment into this trial was very difficult and we had to terminate early, we cannot recommend undertaking a further trial addressing this question in a similar setting. Prof. Dr. Claudia Witt had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Trial registration

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

    PubMed Central

    2012-01-01

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

  14. Acute Dietary Nitrate Supplementation and Exercise Performance in COPD: A Double-Blind, Placebo-Controlled, Randomised Controlled Pilot Study

    PubMed Central

    Curtis, Katrina J.; O’Brien, Katie A.; Tanner, Rebecca J.; Polkey, Juliet I.; Minnion, Magdalena; Feelisch, Martin; Polkey, Michael I.; Edwards, Lindsay M.; Hopkinson, Nicholas S.

    2015-01-01

    Background Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD. Methods We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage. Results 21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve. Conclusions Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype. Trial Registration ISRCTN Registry ISRCTN66099139 PMID:26698120

  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. Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment.

    PubMed

    Polman, C H; Reingold, S C; Barkhof, F; Calabresi, P A; Clanet, M; Cohen, J A; Cutter, G R; Freedman, M S; Kappos, L; Lublin, F D; McFarland, H F; Metz, L M; Miller, A E; Montalban, X; O'Connor, P W; Panitch, H; Richert, J R; Petkau, J; Schwid, S R; Sormani, M P; Thompson, A J; Weinshenker, B G; Wolinsky, J S

    2008-03-25

    The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes. PMID:18362273

  17. Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study.

    PubMed

    Hoerauf, Achim; Specht, Sabine; Büttner, Marcelle; Pfarr, Kenneth; Mand, Sabine; Fimmers, Rolf; Marfo-Debrekyei, Yeboah; Konadu, Peter; Debrah, Alexander Yaw; Bandi, Claudio; Brattig, Norbert; Albers, Anna; Larbi, John; Batsa, Linda; Taylor, Mark J; Adjei, Ohene; Büttner, Dietrich W

    2008-09-01

    In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4-6 weeks, followed by ivermectin (IVM) after 6 months. After 6-27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections. PMID:17999080

  18. Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study

    PubMed Central

    Specht, Sabine; Büttner, Marcelle; Pfarr, Kenneth; Mand, Sabine; Fimmers, Rolf; Marfo-Debrekyei, Yeboah; Konadu, Peter; Debrah, Alexander Yaw; Bandi, Claudio; Brattig, Norbert; Albers, Anna; Larbi, John; Batsa, Linda; Adjei, Ohene; Büttner, Dietrich W.

    2007-01-01

    In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections. PMID:17999080

  19. [Study of analgesic efficacy of propacetamol in the postoperative period using a double blind placebo controlled method].

    PubMed

    Nikoda, V V; Maiachkin, R B

    2002-01-01

    The efficiency and safety of postoperative use of propacetamol was estimated in 30 patients by means of double blind placebo controlled method. The first group consisted of 15 patients to whom propacetamol was introduced intravenously in single dose of 2 g along with patient controlled anesthesia with promedol. Placebo in combination with patient control anesthesia were used in 15 patients from the 2nd group. Intravenous introducing of propacetamol in dose of 2 g in 15 minutes provides relief of pain intensity in postoperative period. So it permits to consider propacetamol as basic non-opioid analgesic. In early postoperative period combination of propacetamol and opioid analgesic (promedol) reduces demands in the latter by 44%. PMID:12462772

  20. [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

  1. Results of a double-blind, placebo-controlled pharmacotherapy trial in alcoholism conducted in Germany and comparison with the US COMBINE study.

    PubMed

    Mann, Karl; Lemenager, Tagrid; Hoffmann, Sabine; Reinhard, Iris; Hermann, Derik; Batra, Anil; Berner, Michael; Wodarz, Norbert; Heinz, Andreas; Smolka, Michael N; Zimmermann, Ulrich S; Wellek, Stefan; Kiefer, Falk; Anton, Raymond F

    2013-11-01

    The results of placebo-controlled trials (RCTs) with acamprosate or naltrexone vary substantially. Those differences have been attributed to differing patient characteristics, recruitment strategies, treatment settings and remuneration systems. We tested these assumptions by comparing a new double-blind, placebo-controlled randomized trial conducted in Germany (called PREDICT Study) with data from the US COMBINE Study. PREDICT was designed according to the protocol of the COMBINE Study. A total of 426 alcohol-dependent patients were compared to 459 COMBINE Study patients corresponding to the treatment cells in PREDICT. All patients received acamprosate, naltrexone or placebo for 3 months (PREDICT) or 4 months (COMBINE). Biweekly manualized 'medical management' to enhance compliance was delivered in both studies. Time until the first occurrence of heavy drinking was the main outcome measure. PREDICT found neither acamprosate nor naltrexone to supply any additional benefit compared with placebo, which is at variance with a positive naltrexone effect being reported in the COMBINE Study. A secondary comparison between both studies showed better overall treatment outcomes in PREDICT, although these patients had been more severely affected than their COMBINE counterparts. The divergence in results may be attributable to basic differences in the treatment environments (such as in-patient pre-treatment versus primary outpatient care). We suggest that identically designed RCTs conducted in different parts of the world may help improve the external validity of RCTs. This approach could be called 'comparative efficacy research'. PMID:23231446

  2. Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: a comparative and a placebo-controlled multicenter study. Vaginal Ring Study Group.

    PubMed

    Casper, F; Petri, E

    1999-01-01

    Local estrogen substitution has been shown to be more appropriate than any systemic application for the treatment of urogenital symptoms of hormone deficiency. The efficacy, safety and acceptability of a new low-dose drug delivery system consisting of an estradiol-releasing silicone vaginal ring was studied in two multicenter trials. In an open-label comparative trial a total of 219 postmenopausal women were randomized to the estradiol-releasing vaginal ring or to estriol suppositories. In terms of efficacy both treatment arms were shown to be equivalent; however, significantly higher rates of acceptability were found for the vaginal ring. In a double-blinded placebo-controlled study a total of 84 patients were randomized to either treatment arm for a period of 24 weeks. The statistically significant improvement of the vaginal epithelial pH and maturation values demonstrated the efficacy of the estradiol-releasing vaginal ring compared to the placebo ring. PMID:10430010

  3. Efficacy of the eradication of Helicobacter pylori infection in patients with chronic urticaria. A placebo-controlled double blind study.

    PubMed

    Gaig, P; García-Ortega, P; Enrique, E; Papo, M; Quer, J C; Richard, C

    2002-01-01

    Helicobacter pylori has been involved in the pathogenesis of chronic idiopathic urticaria (CIU) in patients suffering both CIU and H. pylori infection. We selected 49 patients with 13C urea breath test positive, long-lasting CIU and H. pylori infection; 20 remained symptomatic, had positive urease test or H. pylori histologic identification in gastric biopsy material and accepted to participate in a pacebo-controlled treatment trial. They were randomized for a 7-day, double-blind, placebo-controlled H. pylori eradication treatment with amoxicillin, clarithromycin and omeprazol or placebo. H. pylori eradication was assessed by a second 13C urea breath test six weeks after the end of treatment. We observed a significant improvement of more than 70 % of CIU; baseline clinical score was seen in 4 of the 9 (44 %) patients who eradicated H. pylori after active treatment and in 1 of the 7 (12,3 %) of those who did not (p = 0.19). No clinical differences in CIU characteristics were found between patients with and without improvement. No serious adverse effects were observed in either treatment group. We conclude that the eradication of H. pylori may be useful for patients suffering long-lasting CIU and H. pylori infection, although theses results did not reach statistical significance probably owing to the strict conditions of the recruitment. PMID:12396958

  4. Hyaluronic acid and glucosamine sulfate for adult Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

    PubMed

    Xia, Chuan-Tao; Yu, Fang-Fang; Ren, Feng-Ling; Fang, Hua; Guo, Xiong

    2016-05-01

    To evaluate the efficacy and safety of hyaluronic acid (HA) and glucosamine sulfate (GS) in alleviating symptoms and improving function of Kashin-Beck disease (KBD). A cluster-randomized, placebo-controlled trial was conducted in 150 patients with KBD. Participants were randomly allocated to receive intra-articular injection hyaluronic acid (IAHA) for 4 weeks, oral GS for 12 weeks, or oral placebo for 12 weeks. The primary outcome measures were 20 % and 50 % reductions in pain from baseline measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. Secondary outcome measures included WOMAC index parameters of pain, stiffness, and physical function. The third outcome measure was mean change in Lequence score. HA and GS were effective in reducing WOMAC pain by 20 % (differences of 43.5 % and 25.4 %) and 50 % (differences of 43.4 % and 26.9 %). Both HA and GS significantly reduced WOMAC pain, WOMAC stiffness, and WOMAC normalized score compared with placebo group (all P < 0.05). IAHA was significantly more effective than oral GS in improving WOMAC normalized score (P = 0.034), pain (P = 0.002), stiffness (P = 0.018), and function (P = 0.044). The results indicate that HA and GS were more effective than placebo in treating KBD and HA was more effective than GS. PMID:25388643

  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. Chiropractic spinal manipulative therapy for migraine: a study protocol of a single-blinded placebo-controlled randomised clinical trial

    PubMed Central

    Chaibi, Aleksander; Šaltytė Benth, Jūratė; Tuchin, Peter J; Russell, Michael Bjørn

    2015-01-01

    Introduction Migraine affects 15% of the population, and has substantial health and socioeconomic costs. Pharmacological management is first-line treatment. However, acute and/or prophylactic medicine might not be tolerated due to side effects or contraindications. Thus, we aim to assess the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraineurs in a single-blinded placebo-controlled randomised clinical trial (RCT). Method and analysis According to the power calculations, 90 participants are needed in the RCT. Participants will be randomised into one of three groups: CSMT, placebo (sham manipulation) and control (usual non-manual management). The RCT consists of three stages: 1 month run-in, 3 months intervention and follow-up analyses at the end of the intervention and 3, 6 and 12 months. The primary end point is migraine frequency, while migraine duration, migraine intensity, headache index (frequency x duration x intensity) and medicine consumption are secondary end points. Primary analysis will assess a change in migraine frequency from baseline to the end of the intervention and follow-up, where the groups CSMT and placebo and CSMT and control will be compared. Owing to two group comparisons, p values below 0.025 will be considered statistically significant. For all secondary end points and analyses, a p value below 0.05 will be used. The results will be presented with the corresponding p values and 95% CIs. Ethics and dissemination The RCT will follow the clinical trial guidelines from the International Headache Society. The Norwegian Regional Committee for Medical Research Ethics and the Norwegian Social Science Data Services have approved the project. Procedure will be conducted according to the declaration of Helsinki. The results will be published at scientific meetings and in peer-reviewed journals. Trial registration number NCT01741714. PMID:26586317

  7. Improvement of walking distance by defibrotide in patients with intermittent claudication--results of a randomized, placebo-controlled study (the DICLIS study). Defibrotide Intermittent CLaudication Italian Study.

    PubMed

    Violi, F; Marubini, E; Coccheri, S; Nenci, G G

    2000-05-01

    Defibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide. DICLIS was a double blind, placebo-controlled study which included patients with walking distance autonomy at a standardized treadmill test < or =350 > or =100 meters. A total of 310 patients were randomly allocated to placebo (n = 101), defibrotide 800 mg/day (n = 104) or defibrotide 1200 mg/day (n = 105). During a one year follow-up, the Absolute Walking Distance (AWD) was measured six times (0, 30, 60, 90, 180, 360 days). Similar improvement in walking distance was found in the three groups until the 90th day; thereafter placebo group showed no further increase, while AWD continued to increase in the defibrotide groups. Between the 180th and 360th day visits, AWD was significantly higher (P <0.01) in patients given defibrotide than in patients given placebo. No difference in efficacy was observed between the two dosages of defibrotide. No differences in side effects were observed among the three groups. The results of the present trial suggest that long-term administration of defibrotide improves walking distance in patients with intermittent claudication. PMID:10823260

  8. Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

    PubMed Central

    Milanés-Virelles, María T; García-García, Idrian; Santos-Herrera, Yamilet; Valdés-Quintana, Magalys; Valenzuela-Silva, Carmen M; Jiménez-Madrigal, Gaspar; Ramos-Gómez, Thelvia I; Bello-Rivero, Iraldo; Fernández-Olivera, Norma; Sánchez-de la Osa, Reinaldo B; Rodríguez-Acosta, Carmen; González-Méndez, Lidia; Martínez-Sánchez, Gregorio; López-Saura, Pedro A

    2008-01-01

    Background High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC). Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN) gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. Results Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%). At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before), with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated. Flu-like symptoms

  9. 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

  10. Evaluation of meloxicam (A cox-2 inhibitor) for management of postoperative endodontic pain: a double-blind placebo-controlled study.

    PubMed

    Nekoofar, Mohammad Hosein; Sadeghipanah, Marzieh; Dehpour, Ahmad Reza

    2003-10-01

    Successful management of endodontic pain represents a continuing challenge. The purpose of this randomized, double-blind, placebo-controlled, parallel-group trial was to compare the pain reducing effect of oral preparations of meloxicam, piroxicam, and placebo in endodontic emergency patients. A total of 51 patients who presented to the Tehran University endodontic clinic and one private dental clinic were invited to participate. Patients were asked to evaluate their pretreatment pain with a visual-analog scale. After root canal therapy they were randomly assigned to one of three groups: meloxicam, piroxicam, or placebo. Each patient was sent home with a visual-analog scale to fill out at 8 and 24 h after completion of therapy. The results of this study showed no significant differences between efficacy of meloxicam, piroxicam, and placebo, but a significant effect of the time factor in reducing postoperative pain in all treatment groups was observed. PMID:14606784

  11. [Effectiveness and tolerance of the C3 convertase inhibitor, N-acetyl-aspartyl-magnesium glutamate in perennial rhinitis. Results of a double-blind, placebo-controlled study].

    PubMed

    Harnest, U; Kiehn, R; Sieger, C; Weibel, M A

    1989-02-01

    N-Acetyl-aspartyl magnesium glutamate (Rhinaaxia, NAAGA) is a new antiallergic substance for topical use. The compound covers a bilateral way of action. There is inhibition of the mast cell-degranulation and blocking of the C3-convertase, subsequently followed by a blocked cleavage of the fragments C3a and C5a, respectively. 20 patients suffering from perennial allergic rhinitis were treated according to a randomized double blind placebo-controlled study design. Apart from a nominal documentation of subjective complaints the degree of nasal obstruction was objectively rated via rhinomanometria. The nasal flow rate improved significantly in patients treated with NAAGA and subjective complaints decreased markedly. NAAGA showed to be well tolerated although 6 of 10 patients observed transient "nasal burning". PMID:2659003

  12. [Gamma-linolenic-acid-rich borage seed oil capsules in children with atopic dermatitis. A placebo-controlled double-blind study].

    PubMed

    Borrek, S; Hildebrandt, A; Forster, J

    1997-01-01

    We investigated the effect of gamma-linolenic-acid from borage seed on atopic dermatitis of children. In a placebo-controlled, double-blind manner we studied 24 patients, 3-17 years old. Every patient received 360 mg of gamma-linolenic acid daily, independent from sex and age; the same amount of corn seed-oil served as placebo. After 10 to 14 weeks of treatment there was no improvement of the eczema in the verum phase compared to placebo. Both groups showed improvement while taking placebo. This result could be seen in the objective investigations (Costa-Score, 3 times per treatment period) as well as in the daily patients documentation. The patients whose eczema has improved under borage seed-oil (n = 10) had no special characteristics, so that we could not identify any responder-type. PMID:9244815

  13. The Nightly Use of Sodium Oxybate Is Associated with a Reduction in Nocturnal Sleep Disruption: A Double-Blind, Placebo-Controlled Study in Patients with Narcolepsy

    PubMed Central

    Black, Jed; Pardi, Daniel; Hornfeldt, Carl S.; Inhaber, Neil

    2010-01-01

    Objective: To further explore the effects of sodium oxybate (SXB) administration on nocturnal sleep in narcolepsy patients during a double-blind, placebo-controlled, parallel group study conducted with 228 adult patients with narcolepsy/cataplexy in the United States, Canada, and Europe. Method: Patients were withdrawn from antidepressants and sedative/hypnotics, and then randomized to receive 4.5, 6, or 9 g SXB or placebo nightly for 8 weeks. Patients receiving 6 and 9 g/night doses were titrated to their final dose in weekly 1.5 g increments, while patients receiving placebo were randomized to undergo a similar mock dose titration. The use of stimulant therapy continued unchanged. Changes in sleep architecture were measured using centrally scored nocturnal polysomnograms. Daily diaries were used to record changes in narcolepsy symptoms and adverse events. Results: Following 8 weeks of SXB treatment, study patients demonstrated significant dose-related increases in the duration of stage 3 and 4 sleep, reaching a median increase of 52.5 minutes in patients receiving 9 g nightly. Compared to placebo-treated patients, delta power was significantly increased in all dose groups. Stage 1 sleep and the frequency of nocturnal awakenings were each significantly decreased at the 6 and 9 g/night doses. The changes in nocturnal sleep coincided with significant decreases in the severity and frequency of narcolepsy symptoms. Conclusions: The nightly administration of SXB to narcolepsy patients significantly impacts measures of slow wave sleep, wake after sleep onset, awakenings, total sleep time, and stage 1 sleep in a dose-related manner. The frequency and severity of narcolepsy symptoms decreased with treatment. Citation: Black J; Pardi D; Hornfeldt CS; Inhaber N. The nightly use of sodium oxybate is associated with a reduction in nocturnal sleep disruption: a double-blind, placebo-controlled study in patients with narcolepsy. J Clin Sleep Med 2010;6(6):596-602. PMID:21206549

  14. Dose-Dependent Effects of the Cimicifuga racemosa Extract Ze 450 in the Treatment of Climacteric Complaints: A Randomized, Placebo-Controlled Study.

    PubMed

    Schellenberg, Ruediger; Saller, Reinhard; Hess, Lorenzo; Melzer, Jörg; Zimmermann, Christian; Drewe, Juergen; Zahner, Catherine

    2012-01-01

    Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo). Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic), assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients' self-assessments of general quality of life (QoL), responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65-19.35) score points, P < 0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55-11.39) score points, P = 0.0003 for 6.5 mg). QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women. PMID:23346194

  15. Dose-Dependent Effects of the Cimicifuga racemosa Extract Ze 450 in the Treatment of Climacteric Complaints: A Randomized, Placebo-Controlled Study

    PubMed Central

    Schellenberg, Ruediger; Saller, Reinhard; Hess, Lorenzo; Melzer, Jörg; Zimmermann, Christian; Drewe, Juergen; Zahner, Catherine

    2012-01-01

    Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo). Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic), assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients' self-assessments of general quality of life (QoL), responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65–19.35) score points, P < 0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55–11.39) score points, P = 0.0003 for 6.5 mg). QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women. PMID:23346194

  16. 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

  17. A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease.

    PubMed

    Rascol, Olivier; Ferreira, Joaquim; Nègre-Pages, Laurence; Perez-Lloret, Santiago; Lacomblez, Lucette; Galitzky, Monique; Lemarié, Jean-Christophe; Corvol, Jean-Christophe; Brotchie, Jonathan M; Bossi, Laura

    2012-08-01

    To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation. PMID:21585523

  18. A pilot study of actigraphy as an objective measure of SSRI activation symptoms; results from a randomized placebo controlled psychopharmacological treatment study

    PubMed Central

    Bussing, Regina; Reid, Adam M.; McNamara, Joseph P.H.; Meyer, Johanna M.; Guzick, Andrew G.; Mason, Dana M.; Storch, Eric A.; Murphy, Tanya K.

    2015-01-01

    Selective serotonin reuptake inhibitors (SSRIs) are an efficacious and effective treatment for pediatric obsessive-compulsive disorder (OCD) but have received scrutiny due to a potential side effect constellation called activation syndrome. While recent research introduced a subjective measure of activation syndrome, objective measures have not been tested. This pilot study, using data from a larger randomized-controlled trial, investigated the potential of actigraphy to provide an objective measure of activation symptoms in 44 youths with OCD beginning an SSRI medication regimen. Data were collected over the first four weeks of a multisite, parallel, double-blind, randomized, placebo controlled psychopharmacological treatment study and statistical modeling was utilized to test how activation syndrome severity predicts daily and nightly activity levels. Results indicated that youths with higher activation symptoms had lower daytime activity levels when treatment averages were analyzed; in contrast youths who experienced onset of activation symptoms one week were more likely to have higher daytime and night-time activity ratings that week. Results support actigraphy as a potential objective measure of activation symptoms. Subsequent studies are needed to confirm these findings and test clinical applications for use by clinicians to monitor activation syndrome during SSRI treatment. National Institutes of Health (5UO1 MH078594-01); NCT00382291. PMID:25535011

  19. Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: a randomized, placebo-controlled study. The Dolasetron PONV Prevention Study Group.

    PubMed

    Philip, B K; Pearman, M H; Kovac, A L; Chelly, J E; Wetchler, B V; McKenzie, R; Monk, T G; Dershwitz, M; Mingus, M; Sung, Y F; Hahne, W F; Brown, R A

    2000-01-01

    In a multicentre, randomized, double-blind, placebo-controlled dose-ranging study, 1030 patients undergoing outpatient surgery with general anaesthesia received i.v. dolasetron mesylate (12.5, 25, 50, or 100 mg) or placebo. The principal outcome measure was the proportion of patients who were free of emesis or rescue medication for the 24-h period after the study drug was given; the subsidiary outcome measure was survival time without rescue medication. Effects on nausea were quantified using a visual analogue scale. Compared with placebo, a complete response was significantly higher when all four dolasetron doses were combined (49% vs. 58%, P =0.025). In females, dolasetron, 12.5-mg, dolasetron provided maximum clinical benefit (effectiveness compared with adverse events), with no additional benefit in complete response rates or nausea visual analogue scale scores at higher doses. No significant differences were observed in complete response for any dolasetron dose in males compared with placebo. The majority of adverse events reported were mild or moderate. Dolasetron provided well-tolerated, safe, and effective prophylaxis for post-operative nausea and vomiting with maximum effectiveness observed at a dose of 12.5 mg. PMID:10758440

  20. 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

  1. Placebo Controlled Procedural Trials for Neurological Conditions

    PubMed Central

    Horng, Sam H.; Miller, Franklin G.

    2007-01-01

    Summary Neurological disease has been a central focus in the ongoing ethical debate over the use of invasive placebo controls, especially sham surgery. The risk to research subjects and necessary use of deception involved in these procedures must be balanced against the methodological need to control for bias and the placebo effect. We review a framework formulated for the ethical assessment of sham surgery in the context of research evaluating novel procedures for neurological conditions. Special issues raised include the growing evidence of expectation and conditioning effects in a number of neurological diseases, the escalating scale of risk from different types of invasive placebo interventions, and the increasing use of crossover designs, which allow a switch from placebo to active intervention without additional procedures. PMID:17599718

  2. A double-blind placebo controlled study of risperidone for the treatment of adolescents and young adults with anorexia nervosa: a pilot study

    PubMed Central

    Hagman, Jennifer; Gralla, Jane; Sigel, Eric; Ellert, Swan; Dodge, Mindy; Gardner, Rick; O’Lonergan, Teri; Frank, Guido; Wamboldt, Marianne Z.

    2011-01-01

    Objective The purpose of this double-blind, placebo controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa (AN). Method: Forty females ages 12–21 (mean 16) years, with primary AN in an eating disorders program were randomized to receive risperidone (R, N=18) or placebo (PL, N=22). Subjects completed the Eating Disorder Inventory (EDI-2), Color-A-Person Test, Body Image Software and Multidimensional Anxiety Scale for Children at baseline and regular intervals. Weight, labs, and ECG were monitored. Study medication was started at 0.5 mg daily and titrated upward weekly in 0.5 mg increments to a maximum dose of 4 mg until the subject reached a study end point. Results: Mean dose for the risperidone group was 2.5 mg and in the Placebo group 3 mg, for a mean duration of 9 weeks. R subjects had a significant decrease on the EDI-2 "Drive for Thinness" subscale over the first 7 weeks (p=0.002, effect size 0.88), but this difference was not sustained to study end (p=0.13). The EDI-2 "Interpersonal Distrust" subscale decreased significantly more in R subjects (p=0.03, effect size 0.60). R subjects had increased prolactin levels (week 7, p=0.001). There were no significant differences between groups at baseline or study end for the other rating scales, change in weight or laboratory measures. Conclusions: This study does not demonstrate a benefit for the addition of risperidone in adolescents with AN during the weight restoration phase of care. PMID:21871373

  3. Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study*

    PubMed Central

    Rzany, B; Griffiths, T; Walker, P; Lippert, S; McDiarmid, J; Havlickova, B

    2014-01-01

    Summary Background Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence for their use. An injectable approach with ATX-101 (deoxycholic acid) is under investigation. Objectives To evaluate the efficacy and safety of ATX-101 for the reduction of unwanted SMF. Methods In this double-blind, placebo-controlled, phase III study, 363 patients with moderate/severe SMF were randomized to receive ATX-101 (1 or 2 mg cm−2) or placebo injections into their SMF at up to four treatment sessions ∽28 days apart, with a 12-week follow-up. The co-primary efficacy endpoints were the proportions of treatment responders [patients with ≥ 1-point improvement in SMF on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS)] and patients satisfied with their face and chin appearance on the Subject Self-Rating Scale (SSRS). Secondary endpoints included skin laxity, calliper measurements and patient-reported outcomes. Adverse events were monitored. Results Significantly more ATX-101 recipients met the primary endpoint criteria vs. placebo: on the clinician scale, 59·2% and 65·3% of patients treated with ATX-101 1 and 2 mg cm−2, respectively, were treatment responders vs. 23·0% for placebo (CR-SMFRS;P < 0·001); on the patient scale, 53·3% and 66·1%, respectively, vs. 28·7%, were satisfied with their face/chin appearance (SSRS;P < 0·001). Calliper measurements showed a significant reduction in SMF (P < 0·001), skin laxity was not worsened and patients reported improvements in the severity and psychological impact of SMF with ATX-101 vs. placebo. Most adverse events were transient and associated with the treatment area. Conclusions ATX-101 was effective and well tolerated for nonsurgical SMF reduction. What's already known about this topic? Unwanted submental fat (SMF) is considered aesthetically unappealing. Liposuction and face-lift are effective treatments for SMF reduction but are

  4. Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate

    PubMed Central

    2013-01-01

    Background Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the ‘vigilance regulation model of mania’ which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania. Methods/design A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression–Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-‘Vigilance Algorithm Leipzig’ (VIGALL). Discussion A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives. Trial registration ClinicalTrials.gov: NCT 01541605 PMID:23446109

  5. Decrease in symptoms, blood loss and uterine size with nafarelin acetate before abdominal hysterectomy: a placebo-controlled, double-blind study.

    PubMed

    Ylikorkala, O; Tiitinen, A; Hulkko, S; Kivinen, S; Nummi, S

    1995-06-01

    To evaluate the efficacy and safety of nafarelin before hysterectomy in a prospective placebo-controlled trial, we randomized 188 pre-menopausal women with uterine fibroids (n = 111), menometrorrhagia (n = 58) or pelvic pain (n = 19) to receive either nafarelin (200 micrograms twice daily as a nasal spray) or a placebo for 3 months before abdominal hysterectomy. The data analysis could be performed in 166 women, of whom 107 received nafarelin and 59 a placebo. Nafarelin led to a rise in blood haemoglobin (5.5 g/l) and to a decrease in uterine volume (23.7%). This, however, gave no objective benefit during surgery (similar operative durations and blood losses). The uteri from patients treated with nafarelin (255.5 +/- 12.6 g, mean +/- SD) were significantly lighter (P = 0.029) than those from patients treated with a placebo (346.2 +/- 35.7 g). Histological examination of the fibroids or uteri revealed changes typical for hypo-oestrogenism, but no specific histological pattern could be established. The endometrium was proliferative in 56% and showed mild hyperplastic features in 10% of patients given nafarelin, whereas the respective figures for the placebo group were 41 and 0%. Hot flushes were the most common side-effects, being reported by 61% in the nafarelin group and 35% in the placebo group. Nafarelin can be useful as a pre-surgical adjunct in a patient scheduled for abdominal hysterectomy if there is a need to raise the haemoglobin concentration or to reduce the size of the uterus. PMID:7593517

  6. 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

  7. 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

  8. Placebo-controlled study with OHIO chamber of prophylactic pranlukast for children with Japanese cedar pollinosis: TOPIC-J III study

    PubMed Central

    Hosoya, Kei; Masuno, Satoru; Hashiguchi, Kazuhiro; Okubo, Kimihiro

    2014-01-01

    Objective This double-blind, placebo-controlled comparative study was designed to investigate whether pranlukast dry syrup, a leukotriene receptor antagonist, has a protective effect against priming, controlled pollen exposure, and natural pollen exposure in children with Japanese cedar pollinosis. Research design and methods Thirty children aged 12–15 years with Japanese cedar pollinosis (positive skin test for Japanese cedar pollen), who had suffered from pollinosis for at least 2 years and developed severe nasal obstruction when exposed to Japanese cedar pollen, were enrolled in this study. They were randomly allocated to treatment with pranlukast or placebo orally after breakfast and dinner for 8 weeks during the Japanese cedar pollen season. Soon after the start of the pollen season, all subjects underwent a challenge by exposure for 3 h to Japanese cedar pollen (8000 grains/m3) in an artificial exposure chamber (OHIO chamber). Clinical trial registration The University Hospital Medical Information Network in Japan (UMIN000009840). Main outcome measures The effect of pranlukast was evaluated using self-rating of nasal symptoms by the subjects and measurement of eosinophil cationic protein in nasal discharge specimens. Results Scores for the symptoms of pollinosis were lower in the pranlukast group than in the placebo group during treatment in the priming state, as well as after controlled pollen exposure and natural pollen exposure. Pranlukast significantly improved the score for nasal obstruction, compared with placebo. A correlation was found between changes of the scores for symptoms of pollinosis and changes of the eosinophil cationic protein level. Conclusions These results confirm a protective effect of pranlukast against both priming and challenge (controlled and natural) with Japanese cedar pollen. The present findings suggested that pranlukast dry syrup may be useful for prophylaxis against pollinosis in children.

  9. 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

  10. Fecal Lipid Excretion after Consumption of a Black Tea Polyphenol Containing Beverage-Randomized, Placebo-Controlled, Double-Blind, Crossover Study.

    PubMed

    Ashigai, Hiroshi; Taniguchi, Yoshimasa; Suzuki, Mihoko; Ikeshima, Emiko; Kanaya, Tomoka; Zembutsu, Kanako; Tomita, Shimpei; Miyake, Mika; Fukuhara, Ikuo

    2016-05-01

    Obesity is a serious medical condition worldwide. Inhibition of lipid absorption is very important in preventing obesity. In a previous study, we found that postprandial elevation of triacylglycerol was suppressed by the intake of black tea polyphenol (BTP). We also reported that BTP caused lipid excretion into feces in an animal study. The present study is a clinical trial that examined lipid excretion. In this randomized, placebo-controlled, double-blind, crossover study, in the first test period participants were asked to drink either a beverage containing 55 mg BTP or a control beverage without BTP 3 times a day for 10 d. After an 11-d interval, for the second test period, they then drank the alternate test beverage 3 times a day for 10 d. During the test periods, the participants were asked to eat meals standardized according to calorie and fat content. Stool samples were obtained during the last 3 d of each test period for fecal lipid measurements. Total lipid excretion increased from 5.51±1.73 to 6.87±1.91 g/3 d after BTP intake in comparison with intake of the control beverage. These results indicated that BTP increased lipid excretion. PMID:26887502

  11. Impact of supplemental vitamin K1 administration on postoperative blood component requirements after craniosynostosis repair: a prospective, placebo-controlled, randomized, blinded study.

    PubMed

    Kicker, Jennifer S; Willson, Douglas F; Kelly, Robin L; Jane, John A; Roberts, Sarah E; Conaway, Mark R

    2014-01-01

    Total cranial vault craniosynostosis repairs often require additional blood transfusions in the intensive care unit. Vitamin K1 participates in hepatic production of procoagulant proteins, and body stores of vitamin K1 are limited and dietary dependent. Surgical stress and diet interference may place infants at risk for vitamin K deficiency. Through design of a surgically stratified, randomized, placebo-controlled, blinded pilot study, we evaluated impact of vitamin K1 supplementation on coagulation parameters in infants after craniosynostosis repair. Patients received intramuscular vitamin K1 or placebo coincident with surgical incision. Serum vitamin K1 levels, protein induced in vitamin K absence-prothrombin, and factor VII were obtained at predetermined intervals after surgery. Patients received blood products in the intensive care unit in accordance with transfusion thresholds. Fifteen patients (vitamin K1 = 6, placebo = 9) completed the study procedures. Despite group assignment, patients received an average of 3 postoperative transfusions. Variations were observed with respect to intraoperative resuscitation of patients between comparably trained pediatric anesthesiologists. Thirty-three percent of patients were vitamin K1 deficient on 1 or more laboratory specimens. All breast-fed patients became deficient. Compared with placebo, elevated serum vitamin K1 levels at 6, 12, and 24 hours in the active drug group (P < 0.0001) were not associated with increased factor VII levels or reduced need for postoperative blood products. However, lack of a standardized intraoperative resuscitation plan may contribute to postoperative coagulopathy and is a major study limitation. PMID:24406570

  12. Efficacy of an Extract of Ocimum tenuiflorum (OciBest) in the Management of General Stress: A Double-Blind, Placebo-Controlled Study

    PubMed Central

    Saxena, Ram Chandra; Singh, Rakesh; Kumar, Parveen; Negi, Mahendra P. Singh; Saxena, Vinod S.; Geetharani, Periasamy; Allan, Joseph Joshua; Venkateshwarlu, Kudiganti

    2012-01-01

    A randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of OciBest, an extract of Ocimum tenuiflorum Linn. in symptomatic control of general stress. The participants received either placebo (n = 79) or OciBest (n = 71; 1200 mg of actives per day) for six weeks. The severity of stress-related symptoms was self-evaluated by patients at weeks 0, 2, 4 and 6 of the trial period using a symptom rating scale. After six weeks of intervention, scores of symptoms such as forgetfulness, sexual problems of recent origin, frequent feeling of exhaustion, and frequent sleep problems of recent origin decreased significantly (P ≤ 0.05) in OciBest group as compared with placebo group. Also, the total symptom scores of OciBest group revealed significant reduction (P ≤ 0.05) as compared to placebo group. The overall improvement in OciBest group was found to be 1.6 times or 39% more in the control of general stress symptoms with respect to placebo. No adverse events were reported during the study. The findings revealed that OciBest was found to be effective and well tolerated by all the patients over the six weeks of study period. PMID:21977056

  13. 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

  14. Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

    PubMed

    Park, Sat Byul; Kim, Kyu-Nam; Sung, Eunju; Lee, Suk Young; Shin, Ho Cheol

    2016-05-01

    Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS. PMID:26911970

  15. 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

  16. 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

  17. 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. PMID:24264227

  18. 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

  19. The effects of repeated administration of camphor-crataegus berry extract combination on blood pressure and on attentional performance - a randomized, placebo-controlled, double-blind study.

    PubMed

    Erfurt, L; Schandry, R; Rubenbauer, S; Braun, U

    2014-09-25

    The present study investigated the effects of repeated administration of Korodin(®), a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin(®) or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin(®) administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin(®). The excellent tolerability and safety of Korodin(®), even after a total consumption of 80 drops, was confirmed. PMID:25172798

  20. A double-blind, placebo controlled study of the effect of the specific histamine H1-receptor antagonist, terfenadine, in chronic severe asthma.

    PubMed Central

    Wood-Baker, R; Smith, R; Holgate, S T

    1995-01-01

    1. The characteristic changes seen in asthma are widely regarded as being caused by local mediator release in the airways, with histamine the first putative mediator in asthma to be identified. 2. We performed a double-blind, randomised, placebo-controlled crossover trial of the effect of 4 weeks treatment with terfenadine 120 mg twice daily in chronic severe asthma. 3. Forty-two subjects (20 male and 22 female) completed the 10 week study. 4. Terfenadine had no significant treatment effect on the primary efficacy variables measured. Mean (95% CI) measurements for terfenadine vs placebo treatment periods were 1.5 vs 1.5 (-0.3, 0.3) l for FEV1, 259 vs 260 (-42, 40) l min-1 for morning PEF and 0.8 vs 0.8 (-0.3, 0.3) for global symptom scores. 5. Bronchodilator use and sleep disturbance, the secondary efficacy variables studied, showed an improvement during terfenadine treatment but this only reached statistical significance for the number of times subjects awoke from sleep (P = 0.04). 6. There was a similar frequency of minor adverse effects reported during placebo (13.6%) and terfenadine (16.7%) treatments. 7. Addition of the potent and specific histamine H1-receptor antagonist terfenadine to maintenance asthma treatment had no significant therapeutic benefit in this group of chronic severe asthmatics. PMID:7654486

  1. 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. PMID:17121317

  2. Positive Psychology Interventions Addressing Pleasure, Engagement, Meaning, Positive Relationships, and Accomplishment Increase Well-Being and Ameliorate Depressive Symptoms: A Randomized, Placebo-Controlled Online Study

    PubMed Central

    Gander, Fabian; Proyer, René T.; Ruch, Willibald

    2016-01-01

    Seligman (2002) suggested three paths to well-being, the pursuit of pleasure, the pursuit of meaning, and the pursuit of engagement, later adding two more, positive relationships and accomplishment, in his 2011 version. The contribution of these new components to well-being has yet to be addressed. In an online positive psychology intervention study, we randomly assigned 1624 adults aged 18–78 (M = 46.13; 79.2% women) to seven conditions. Participants wrote down three things they related to either one of the five components of Seligman's Well-Being theory (Conditions 1–5), all of the five components (Condition 6) or early childhood memories (placebo control condition). We assessed happiness (AHI) and depression (CES-D) before and after the intervention, and 1-, 3-, and 6 months afterwards. Additionally, we considered moderation effects of well-being levels at baseline. Results confirmed that all interventions were effective in increasing happiness and most ameliorated depressive symptoms. The interventions worked best for those in the middle-range of the well-being continuum. We conclude that interventions based on pleasure, engagement, meaning, positive relationships, and accomplishment are effective strategies for increasing well-being and ameliorating depressive symptoms and that positive psychology interventions are most effective for those people in the middle range of the well-being continuum. PMID:27242600

  3. Efficacy of a Standardized Extract of Prunus mume in Liver Protection and Redox Homeostasis: A Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Beretta, Alberto; Accinni, Roberto; Dellanoce, Cinzia; Tonini, Annamaria; Cardot, Jean-Michel; Bussière, Anthony

    2016-06-01

    The antioxidant, anti-inflammatory and hepatoprotective effects of Prunus mume (PM) have previously been demonstrated. This double-blind, placebo-controlled study was designed to evaluate the influence of two doses of a food supplement, made of 150 mg of a standardized PM extract on liver transaminases, lipid profile, glycemia, neopterin and reduced and oxidized thiols in plasma and erythrocytes, during a 3-month treatment period, in healthy subjects with transaminases levels between 20 and 40 UI/L. Forty-five subjects (56.0 ± 11.6 years) were enrolled. The results showed a beneficial and statistically significant effect versus placebo of PM extract on liver function, with a decrease versus baseline in alanine aminotransferase (47%), aspartate aminotransferase (7%), gamma-glutamyl transpeptidase (15%) and glycemia (11%). The lipid profile modification was also positive with an increase versus baseline in HDL cholesterol (13%), and a decrease in LDL/HDL ratio (12%) and triglycerides (8%). The antioxidant action of PM translated into a decrease in oxidized glutathione, reduced/oxidized cysteine-glycine, oxidized cysteine (intracellular pro-oxidant) and neopterin (inflammation biomarker), was associated with an increase in reduced glutathione. These results are in favor of the use of a standardized extract of P. mume for the support of liver health and prevention of common metabolic and inflammation-based diseases. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26952142

  4. Effect of Korean Red Ginseng supplementation on dry eye syndrome in glaucoma patients – A randomized, double-blind, placebo-controlled study

    PubMed Central

    Bae, Hyoung Won; Kim, Ji Hyun; Kim, Sangah; Kim, Minkyo; Lee, Naeun; Hong, Samin; Seong, Gong Je; Kim, Chan Yun

    2014-01-01

    Background Many patients with glaucoma have difficulty using antiglaucoma eye drops because of dry eye symptom. In this prospective, randomized, double-blind, placebo-controlled study, we evaluated the effect of Korean Red Ginseng on dry eye syndrome in patients with glaucoma treated with antiglaucoma eye drops. Methods Forty-nine participants were allocated to the Korean Red Ginseng (3 g/day; n = 24) or placebo (n = 25) groups for 8 weeks. Tear film stability, fluorescein corneal staining, conjunctival hyperemia, tear production, grade of meibomian gland dysfunction, and dry eye questionnaire (Ocular Surface Disease Index) were evaluated at baseline and on completion of the treatment. Results Almost all patients displayed dry eye symptoms and signs at baseline. After the 8-week intervention, Korean Red Ginseng supplementation significantly improved the tear film stability and total Ocular Surface Disease Index score, as compared to placebo (p < 0.01). Conclusion Korean Red Ginseng supplementation may provide an additional treatment option for dry eye and patients with glaucoma using antiglaucoma eye drops. PMID:25535471

  5. Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study

    PubMed Central

    Anton, Stephen D.; Embry, Chelsea; Marsiske, Michael; Lud, Xiaomin; Doss, Hani; Leeuwenburgh, Christiaan; Manini, Todd M.

    2014-01-01

    Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73 ± 7 years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300 mg/day), and (3) high dose resveratrol (1000 mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90 days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps < 0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300 mg/day and 1000 mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials. PMID:24866496

  6. 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

  7. A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria.

    PubMed

    Burton, B; Grant, M; Feigenbaum, A; Singh, R; Hendren, R; Siriwardena, K; Phillips, J; Sanchez-Valle, A; Waisbren, S; Gillis, J; Prasad, S; Merilainen, M; Lang, W; Zhang, C; Yu, S; Stahl, S

    2015-03-01

    Symptoms of attention deficit-hyperactivity disorder (ADHD), particularly inattention, and impairments in executive functioning have been reported in early and continuously treated children, adolescents, and adults with phenylketonuria (PKU). In addition, higher blood phenylalanine (Phe) levels have been correlated with the presence of ADHD symptoms and executive functioning impairment. The placebo-controlled PKU ASCEND study evaluated the effects of sapropterin therapy on PKU-associated symptoms of ADHD and executive and global functioning in individuals who had a therapeutic blood Phe response to sapropterin therapy. The presence of ADHD inattentive symptoms and executive functioning deficits was confirmed in this large cohort of 206 children and adults with PKU, of whom 118 responded to sapropterin therapy. In the 38 individuals with sapropterin-responsive PKU and ADHD symptoms at baseline, sapropterin therapy resulted in a significant improvement in ADHD inattentive symptoms in the first 4 weeks of treatment, and improvements were maintained throughout the 26 weeks of treatment. Sapropterin was well-tolerated with a favorable safety profile. The improvements in ADHD inattentive symptoms and aspects of executive functioning in response to sapropterin therapy noted in a large cohort of individuals with PKU indicate that these symptoms are potentially reversible when blood Phe levels are reduced. PMID:25533024

  8. Positive Psychology Interventions Addressing Pleasure, Engagement, Meaning, Positive Relationships, and Accomplishment Increase Well-Being and Ameliorate Depressive Symptoms: A Randomized, Placebo-Controlled Online Study.

    PubMed

    Gander, Fabian; Proyer, René T; Ruch, Willibald

    2016-01-01

    Seligman (2002) suggested three paths to well-being, the pursuit of pleasure, the pursuit of meaning, and the pursuit of engagement, later adding two more, positive relationships and accomplishment, in his 2011 version. The contribution of these new components to well-being has yet to be addressed. In an online positive psychology intervention study, we randomly assigned 1624 adults aged 18-78 (M = 46.13; 79.2% women) to seven conditions. Participants wrote down three things they related to either one of the five components of Seligman's Well-Being theory (Conditions 1-5), all of the five components (Condition 6) or early childhood memories (placebo control condition). We assessed happiness (AHI) and depression (CES-D) before and after the intervention, and 1-, 3-, and 6 months afterwards. Additionally, we considered moderation effects of well-being levels at baseline. Results confirmed that all interventions were effective in increasing happiness and most ameliorated depressive symptoms. The interventions worked best for those in the middle-range of the well-being continuum. We conclude that interventions based on pleasure, engagement, meaning, positive relationships, and accomplishment are effective strategies for increasing well-being and ameliorating depressive symptoms and that positive psychology interventions are most effective for those people in the middle range of the well-being continuum. PMID:27242600

  9. Scotopic sensitivity/Irlen syndrome and the use of coloured filters: a long-term placebo controlled and masked study of reading achievement and perception of ability.

    PubMed

    Robinson, G L; Foreman, P J

    1999-08-01

    This study investigated the effects of using coloured filters on reading speed, accuracy, and comprehension as well as on perception of academic ability. A double-masked, placebo-controlled crossover design was used, with subjects being assessed over a period of 20 mo. There were three treatment groups (Placebo filters, Blue filters, and Optimal filters) involving 113 subjects with "reading difficulties", ranging in age from 9.2 yr. to 13.1 yr. and with an average discrepancy between chronological age and reading age of 1.8 yr. The 35 controls (who did not use coloured filters) ranged in age from 9.4 yr. to 12.9 yr., with an average discrepancy between chronological age and reading age of 2.1 yr. The treatment groups increased at a significantly greater rate than the control group in reading accuracy and reading comprehension but not for speed of reading. For self-reported perception of academic ability, two of the three treatment groups showed significantly greater increases than the control group. The larger improvements for treatment groups in reading comprehension may be related to a reduction in print and background distortions allowing attention to be directed to the processing of continuous text rather than to the identification of individual words. A reduction in print distortion, however, may not be sufficient to generate improved word-identification skills without additional remedial support, and this may be indicated by the nonsignificant increase in rate of reading. PMID:10544403

  10. Scotopic sensitivity/Irlen syndrome and the use of coloured filters: a long-term placebo-controlled study of reading strategies using analysis of miscue.

    PubMed

    Robinson, G L; Foreman, P J

    1999-02-01

    This study investigated the long-term effects of using coloured filters on the frequency and type of errors in oral reading. A double-masked, placebo-controlled crossover experimental design was used, with subjects being assessed over a period of 20 months. There were three experimental groups (Placebo tints, Blue tints, and Diagnosed tints) involving 113 subjects with reading difficulties, ranging in age from 9.2 yr. to 13.1 yr. The 35 controls (ranging in age from 9.4 yr. to 12.9 yr.) had reading difficulties but did not require coloured filters. There was a significant improvement for all groups in the accuracy of miscues over the period, although experimental groups over-all did not improve at a significantly different rate than the control group. The failure to find significantly greater improvement for the experimental groups over the control group for the total period, despite subjects' reports of improved print clarity, may be partly related to the lack of effective letter-sound analysis and synthesis skills and to the use of a word-identification strategy of guessing based on partial visual analysis. PMID:10214632

  11. Comparison of oral and vaginal misoprostol for cervical ripening before manual vacuum aspiration of first trimester pregnancy under local anesthesia: a randomized placebo-controlled study.

    PubMed

    Cakir, Leyla; Dilbaz, Berna; Caliskan, Eray; Dede, F Suat; Dilbaz, Serdar; Haberal, Ali

    2005-05-01

    The objective of this prospective randomized placebo-controlled study was to determine the effectiveness of 400 mug oral and 400 mug vaginal misoprostol administration for cervical priming 3 h prior to manual vacuum aspiration (MVA) under local anesthesia for voluntary termination of pregnancy before 10 weeks of gestation in comparison with placebo oral or placebo vaginal administration (n=40 in each group). Postmedication cervical dilatation was similar in the oral (mean, 6.6+/-1.5) and vaginal (mean, 7.2+/-0.8) misoprostol groups but significantly higher compared with the oral (mean, 3.4+/-0.2) and vaginal (mean, 3.6+/-1.9) placebo groups. Duration of the procedure was also significantly shorter in the misoprostol groups in comparison with their placebo counterparts. Preoperative bleeding and side effects were more common in the misoprostol groups, but none required medical intervention. Intraoperative bleeding was less in the vaginal misoprostol group compared with the placebo groups. There was no significant difference in terms of visual analogue scores during the procedure, patient satisfaction, days of postoperative bleeding and rate of postoperative complications among the groups. Cervical priming with misoprostol administered orally or vaginally 3 h before MVA for termination of pregnancy under local anesthesia facilitates the procedure by decreasing the need for cervical dilatation and by shortening its duration without improving patients' pain perception and satisfaction mainly due to side effects. PMID:15854633

  12. 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.

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

    PubMed Central

    Seitsalo, Hubertus; Niemelä, Raija K; Marinescu-Gava, Magdalena; Vuotila, Tuija; Tjäderhane, Leo; Salo, Tuula

    2007-01-01

    Background Matrix metalloproteinases (MMPs) are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS). Low-dose doxycycline (LDD) inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients. This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately. Results Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p < 0.05). The differences may, however, reflect normal fluctuation of symptoms in SS patients. Conclusion LDD may not be useful in reducing the primary SS symptoms. PMID:18163919

  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. Increasing work-place healthiness with the probiotic Lactobacillus reuteri: A randomised, double-blind placebo-controlled study

    PubMed Central

    Tubelius, Py; Stan, Vlaicu; Zachrisson, Anders

    2005-01-01

    Background Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730) on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections. Methods 262 employees at TetraPak in Sweden (day-workers and three-shift-workers) that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 108 Colony Forming Units of L. reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive L. reuteri and 87 received placebo. Results In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the L. reuteri group (p < 0.01). The frequency of sick-days was 0.9% in the placebo group and 0.4% in the L. reuteri group (p < 0.01). Among the 53 shift-workers, 33% in the placebo group reported sick during the study period as compared with none in the L. reuteri group(p < 0.005). PMID:16274475

  17. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to Counteract Olanzapine-Associated Weight Gain.

    PubMed

    Barak, Nir; Beck, Yaffa; Albeck, Joseph H

    2016-06-01

    Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted. PMID:27028981

  18. Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation

    PubMed Central

    Bourbeau, Jean; Lavoie, Kim L; De Sousa, Dorothy; Erzen, Damijan; Hamilton, Alan; Maltais, François; Troosters, Thierry; Leidy, Nancy

    2016-01-01

    Introduction Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study. Methods and analysis PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies. Ethics and dissemination The study has been approved by the relevant Institutional Review Boards, Independent Ethics

  19. A Randomized, Placebo-Controlled Study of Once-Daily Atomoxetine in the School Setting in Children with ADHD

    ERIC Educational Resources Information Center

    Weiss, Margaret; Tannock, Rosemary; Kratochvil, Christopher; Dunn, David; Velez-Borras, Jesus; Thomason, Christine; Tamura, Roy; Kelsey, Douglas; Stevens, Linda; Allen, Albert J.

    2005-01-01

    Objective: Five studies have demonstrated the effectiveness of atomoxetine compared with placebo in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) based on parent reports. The primary objective of this clinical trial was to assess the efficacy of once-daily atomoxetine compared with placebo using teacher reports. Method: One…

  20. 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

  1. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease

    PubMed Central

    Hager, Klaus; Baseman, Alan S; Nye, Jeffrey S; Brashear, H Robert; Han, John; Sano, Mary; Davis, Bonnie; Richards, Henry M

    2014-01-01

    Background Currently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model. Results In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18

  2. 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

  3. A possible effect of methylphenidate on state anxiety: A single dose, placebo controlled, crossover study in a control group.

    PubMed

    Segev, Aviv; Gvirts, Hila Zahava; Strouse, Kevin; Mayseless, Naama; Gelbard, Hagar; Lewis, Yael Doreen; Barnea, Yael; Feffer, Kfir; Shamay-Tsoory, Simone G; Bloch, Yuval

    2016-07-30

    Methylphenidate affects state-anxiety in ADHD patients. The current study examines the effect of Methylphenidate on state-anxiety in healthy subjects. In a cross-over, randomized, controlled, double-blind study, 36 healthy subjects received either Methylphenidate or placebo. As a group, no change in state-anxiety was detected with Methylphenidate. However, participants reporting higher anxiety levels experienced a significant and specific state-anxiety reduction following Methylphenidate. Moreover, a strong negative correlation was found between the initial-level of anxiety and net-change in state-anxiety. These changes were unrelated to self-perceived attention levels. Our results point to the state-dependent effects of Methylphenidate on anxiety. PMID:27183109

  4. Central mechanisms of controlled-release metoprolol in migraine: a double-blind, placebo-controlled study.

    PubMed

    Siniatchkin, M; Andrasik, F; Kropp, P; Niederberger, U; Strenge, H; Averkina, N; Lindner, V; Stephani, U; Gerber, W-D

    2007-09-01

    beta-Blockers are widely used in the prophylaxis of migraine and have been described as very effective drugs in many studies. Some investigators have demonstrated that the clinical improvement of migraine corresponds to the normalization of the contingent negative variation (CNV), a slow cortical potential measuring cortical information processing. However, most of these studies have contained a variety of methodological pitfalls, which we attempted to address in the current study. Twenty patients suffering from migraine without aura were randomly divided into two groups. The groups were treated either with controlled-release metoprolol or placebo for 3 months, using a double-blind design. Twice before and once after each month of the treatment the CNV was recorded. After 3 months, a significant reduction of migraine frequency, duration and intensity was demonstrated for the metoprolol compared with the placebo group. The CNV was characterized by a marked reduction of the amplitude of the total CNV and postimperative negative variation and normalization of the eartly CNV habituation following treatment. Therefore, metoprolol may exert its prophylactic effect in migraine through the influence on cortical information processing and excitability represented by the CNV. PMID:17680819

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

    PubMed Central

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

    2008-01-01

    Aims The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. Methods This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18–60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day−1. Results One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day−1 of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. Conclusions The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. What is already known about this subject The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. What this study adds The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH

  6. 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

  7. Treatment of Idiopathic Parkinson's Disease with Traditional Chinese Herbal Medicine: A Randomized Placebo-Controlled Pilot Clinical Study

    PubMed Central

    Kum, Wan Fung; Durairajan, Siva Sundara Kumar; Bian, Zhao Xiang; Man, Sui Cheung; Lam, Yuen Chi; Xie, Li Xia; Lu, Jia Hong; Wang, Yan; Huang, Xian Zhang; Li, Min

    2011-01-01

    The objective of this clinical study is to examine the effects of a Chinese herbal medicine formula (Jia Wei Liu Jun Zi Tang: JWLJZT) on motor and non-motor symptoms, and on complications of conventional therapy in idiopathic Parkinson's disease (PD), using an add-on design. Fifty-five patients with PD were randomly allocated to receive either Chinese herbal medicine or placebo for 24 weeks. Primary outcome measure was the 39-item Parkinson's Disease Questionnaire (PDQ-39). Secondary outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Short-Form-36 Health Survey (SF-36), Geriatric Depression Scale (GDS), home diaries, and a range of category rating scales. JWLJZT resulted in a significant improvement in the UPDRS IVC when compared with placebo at 12 weeks (P = .039) and 24 weeks (P = .034). In addition, patients in the Chinese herbal medicine group also showed significant improvement in PDQ-39 communication scores at 12 weeks (P = .024) and 24 weeks (P = .047) when compared with the placebo group. There were no significant differences between treatment and control groups for SF-36 variables, GDS score or the mean daily “on-off” time. One case of mild diarrhea was noted in the treatment group. The findings suggest that JWLJZT can relieve some non-motor complications of conventional therapy and improve the communication ability in patients with PD. The results of this pilot study warrant larger multi-center clinical studies to assess long-term efficacy and tolerability of JWLJZT, and to elucidate the mechanisms by which it affects PD function. PMID:19692449

  8. 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

  9. A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder

    PubMed Central

    Ionescu, Dawn F.; Fava, Maurizio; Kim, Daniel Ju Hyung; Baer, Lee; Shelton, Richard C.; Cusin, Cristina

    2016-01-01

    Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone’s safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability. Methods: A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure. Results: There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order (p = 0.77). Conclusions: Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability. PMID:26913173

  10. Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study.

    PubMed

    Butterfield, Max E; Saal, Jaime; Young, Benjamin; Young, Joel L

    2016-02-28

    The purpose of this study was to examine the efficacy of an extended release guanfacine hydrochloride supplement relative to a placebo supplement in adults (19-62) with ADHD and a sub-optimal response to a stimulant-only treatment program. The study's primary outcome measures were the Attention Deficit Hyperactivity Disorder Rating Scale and the Clinical Global Impression - Severity. Twenty-six adults who met criteria for attention deficit hyperactivity disorder and sub-optimal functioning were randomly assigned to supplement their existing psychostimulant treatment regimen with either a titrated dose (1-6mg) of extended release guanfacine hydrochloride or a matching placebo for a 10-week trial. The data were analyzed with standard mixed model analysis of variance procedures, and participants in both the investigational agent group and the placebo group showed statistically significant improvement in their symptoms and functioning over the course of the trial. The treatments did not differ in terms of their efficacy, safety, or tolerability. Although these results do suggest that both treatments were associated with clinical improvement, the possible impacts of socially desirable responding and regression to the mean on these results are discussed. PMID:26730446

  11. A double-blind, placebo-controlled study of N-acetyl cysteine plus naltrexone for methamphetamine dependence.

    PubMed

    Grant, Jon E; Odlaug, Brian L; Kim, Suck Won

    2010-11-01

    Reducing both glutamatergic and dopaminergic drive in the nucleus accumbens may offer complementary mechanisms by which to reduce drug cravings. This 8-week study sought to examine the efficacy of a combination of a glutamate modulator, N-acetyl cysteine (NAC), plus the opioid antagonist, naltrexone, compared to placebo in the treatment of methamphetamine dependence. Thirty-one subjects with methamphetamine dependence (mean age 36.8 ± 7.12 years; 29% female) were randomly assigned in a 1:1 fashion to NAC plus naltrexone or placebo and returned for one post-baseline visit. The Penn Craving Scale was the primary outcome measure. Self-report methamphetamine use frequency and urine toxicology were secondary measures. NAC plus naltrexone failed to demonstrate statistically significant differences from placebo on primary and secondary outcomes. The current study failed to demonstrate greater efficacy for NAC plus naltrexone compared to placebo. Given the small sample size, the statistical power to detect significant effects of active treatment versus placebo was limited. The question of whether a larger, well-powered sample would have detected differences between NAC plus naltrexone and placebo deserves further examination. PMID:20655182

  12. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome.

    PubMed

    Rao, A Venket; Bested, Alison C; Beaulne, Tracey M; Katzman, Martin A; Iorio, Christina; Berardi, John M; Logan, Alan C

    2009-01-01

    Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract. PMID:19338686

  13. High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study.

    ERIC Educational Resources Information Center

    Findling, Robert L.; Maxwell, Kathleen; Scotese-Wojtila, Lynette; Huang, Jie; Yamashita, Toyoko; Wiznitzer, Max

    1997-01-01

    Evaluation of high doses of pyridoxine and magnesium in a 10-week double-blind placebo-controlled trial with 10 patients (mean age 6 years) having autism concluded that the high doses used were ineffective in ameliorating autistic behaviors. (DB)

  14. Double-Blind, Placebo-Controlled, Crossover Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in College Students with ADHD

    ERIC Educational Resources Information Center

    DuPaul, George J.; Weyandt, Lisa L.; Rossi, Joseph S.; Vilardo, Brigid A.; O'Dell, Sean M.; Carson, Kristen M.; Verdi, Genevieve; Swentosky, Anthony

    2012-01-01

    Objective: To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design. Method: Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five…

  15. Hyaluronic acid dressing (Healoderm) in the treatment of diabetic foot ulcer: A prospective, randomized, placebo-controlled, single-center study.

    PubMed

    Lee, Moses; Han, Seung Hwan; Choi, Woo Jin; Chung, Kwang Ho; Lee, Jin Woo

    2016-05-01

    Fast and complete healing of a diabetic foot ulcer (DFU) is challenging due to the hostile wound healing environment of the diabetic patients. As a part of a multimodal treatment approach, advanced dressing material using hyaluronic acid (HA) has been found to be effective. However, previous studies have used HA with additional biologics, which interferes in determining the true clinical effect of HA in DFU. To examine the sole effectiveness of HA in DFU treatment, a prospective, randomized, placebo-controlled, single-center study was conducted using an HA dressing without additional substances. Thus, 34 patients who met the inclusion criteria were randomized into two groups (the study group: HA dressing material; the control group: conventional dressing material). During the 12-week study period, complete ulcer healing rate was evaluated as a primary endpoint. Additionally, healing velocity and the mean duration for achieving a 50% ulcer size reduction was compared between the two groups as a secondary endpoint. At the end of the study, the study group presented a significantly higher complete healing rate as compared to that in the control group [84.6% (11/13), 41.6% (5/12), respectively, P = 0.041]. Additionally, faster ulcer healing velocity and shorter mean duration for achieving a 50% ulcer size reduction were observed in the study group (P = 0.022 and 0.004, respectively). The Kaplan-Meier survival analysis for the median time for 50% ulcer healing rate also showed a significantly shorter duration in the study group (21 days vs. 39 days, P = 0.0127). Finally, there were no adverse events related to the dressing materials used in the study. As a major component of the extracellular matrix, this study supports the safety and efficacy of a pure HA dressing without additional substances in treating DFU. PMID:26972358

  16. Comparison Between Intraperitoneal and Intravenous Lidocaine for Postoperative Analgesia After Elective Abdominal Hysterectomy, a Double-Blind Placebo Controlled Study

    PubMed Central

    Samimi, Saghar; Taheri, Arman; Davari Tanha, Fatemeh

    2015-01-01

    Objective: To compare the efficacy of intravenous and intraperitoneal injection of lidocaine and normal saline in relieving postoperative pain after elective abdominal hysterectomy. Materials and methods: For this double-blind randomized controlled study 109 patients undergoing elective abdominal hysterectomy were randomly allocated to three groups :1) IV group (intravenous injection group) received intravenous lidocaine %2 bolus 1.5mg/kg 30 min before incision and then a continuous lidocaine infusion of 2mg/kg and before the wound closure an intraperitoneal injection of N/S , 2) IP group (intraperitoneal group) received intravenous N/S and intraperitoneal lidocaine 3mg/kg , 3) P group (placebo, N/S) received both intravenous and intraperitoneal N/S. The pain scores (VAS) at rest, total morphine consumption , the time to first need for rescue analgesic ,incidence of lidocaine related adverse effects and nausea and vomiting were recorded at 0,2,4,8,12 and 24 hrs postoperatively. Results: The VAS scores were significantly lower in IP and IV groups compared with placebo (p = 0.001). Total consumption of morphine (p = 0.001) and time to firs request of recue analgesic (p = 0.001) were lower too in IP and IV groups.Incidence of vomiting was comparable between groups (p < 0.05) but nausea was higher in control group (p > 0.05).There were not notable lidocaine-related adverse effects. IP and IV groups were not statistically different for all investigated variables. Conclusion: This study showed lidocaine administration both intravenously and intraperitoneally are effective in reducing the postoperative pain and also have opioid sparing effect and can be safely used in elective abdominal hysterectomy without any major adverse effects. PMID:27047566

  17. A randomized, placebo-controlled study investigating the nicotinic α7 agonist, RG3487, for cognitive deficits in schizophrenia.

    PubMed

    Umbricht, Daniel; Keefe, Richard S E; Murray, Stephen; Lowe, David A; Porter, Richard; Garibaldi, George; Santarelli, Luca

    2014-06-01

    Effective treatments for cognitive impairment associated with schizophrenia (CIAS) remain an unmet need. Nicotinic α7 receptor agonists may be effective in CIAS. This 8-week (week 1, inpatient; weeks 2-8, outpatient), double-blind, randomized study used Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) guidelines to investigate the nicotinic α7 partial agonist RG3487 (formerly MEM3454) in CIAS; 215 patients with chronic stable schizophrenia received placebo or RG3487 (5, 15, or 50 mg) added to ongoing treatment with risperidone, paliperidone, or aripiprazole. Primary end point was baseline to week 8 change in MATRICS Consensus Cognitive Battery (MCCB) composite t-score. Secondary outcomes were change in MCCB domain and negative symptom assessment (NSA) scores. The study did not allow for evaluation of nonsmokers. Each RG3487 dose was evaluated using a mixed-effects model repeated measures approach. Mean (SD) baseline MCCB composite t-score was 28.3 (12.0). No significant effect on MCCB composite t-scores was observed with RG3487 (adjusted mean difference (SE) vs placebo: 5 mg: 0.11 (1.39); 15 mg: -1.95 (1.39); 50 mg: -1.13 (1.37); p = 0.2-0.9). RG3487 did not improve MCCB domain scores. In a post hoc analysis of patients with moderate negative symptoms, 5 and 50 mg RG3487 vs placebo significantly improved NSA total (-4.45 (p = 0.04) and -4.75 (p = 0.02), respectively) and global (-0.39 (p = 0.04) and -0.55 (p = 0.003), respectively) scores. The MCCB did not lead to higher than expected patient withdrawal. RG3487 was generally well tolerated. In patients with stable schizophrenia, RG3487 did not improve cognitive deficits, as assessed by the MCCB; however, in patients with moderate negative symptoms, a post hoc analysis revealed significant improvement of negative symptoms. PMID:24549101

  18. Decreased urinary glycosaminoglycan excretion following alfuzosin treatment on ureteral stent-related symptoms: a prospective, randomized, placebo-controlled study.

    PubMed

    Liu, Shucheng; Yu, Ying; Gao, Yang; Yang, Xiong; Pang, Zili

    2016-04-01

    The objectives of the study were to evaluate changes in ureteral stent-related symptoms and urinary glycosaminoglycan (GAG) excretion after alfuzosin treatment, and to further investigate the relationship between stent-related symptoms and loss of urinary GAGs. Seventy consecutive patients scheduled for unilateral retrograde ureteroscopy with stent placement were recruited. Patients were randomly assigned to treatment with alfuzosin 10 mg/day or placebo for 3 weeks starting on the third postoperative day. The ureteral stent was removed when treatment stopped. International Prostate Symptom Score (IPSS), visual analog scale (VAS) score, and urinary GAG excretion were determined before treatment at 1, 2, and 3 weeks after treatment, and at 3 weeks after stent removal. Fifty-nine patients completed the study. IPSS, VAS score, and urinary GAG excretion were significantly lower in the alfuzosin group, compared with the placebo group, at 1, 2, and 3 weeks after treatment (P < 0.01). In both groups, IPSS, VAS score, and urinary GAG excretion were significantly lower at 3 weeks after stent removal compared with those before stent removal. No significant differences in IPSS, VAS score, or urinary GAG excretion were observed between the two groups at baseline and 3 weeks after stent removal (P > 0.05). Positive correlations were found between urinary GAG excretion (R (2) = 0.65, P < 0.001) and IPSS and between urinary GAG excretion and VAS score (R (2) = 0.33, P < 0.001). Stent placement contributes to loss of urinary GAGs. However, alfuzosin effectively reduces such loss and improves ureteral stent-related symptoms. Loss of urinary GAGs plays a role in these symptoms. PMID:26242466

  19. Inhaled loxapine and intramuscular lorazepam in healthy volunteers: a randomized placebo-controlled drug-drug interaction study.

    PubMed

    Spyker, Daniel A; Cassella, James V; Stoltz, Randall R; Yeung, Paul P

    2015-12-01

    Pharmacodynamic effects and safety of single-dose inhaled loxapine administered via the Staccato(®) system and intramuscular (IM) lorazepam in combination versus each agent alone were compared in a randomized, double-blind, crossover study in healthy volunteers. Subjects received: inhaled loxapine 10 mg + IM lorazepam 1 mg; inhaled loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato placebo in random order, each separated by a 3-day washout. Primary endpoints were maximum effect (minimum value) and area under the curve (AUC) from baseline to 2 h post treatment for respirations/min and pulse oximetry. Least-squares means (90% confidence interval [CI]) for concomitant treatment versus each agent alone were derived and equivalence (no difference) confirmed if the 90% CI was within 0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual analog scale), and adverse events (AEs) were recorded. All 18 subjects (mean age, 20.4 years; 61% male) completed the study. There was no difference between inhaled loxapine + IM lorazepam and either agent alone on respiration or pulse oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min ratios. BP and HR were no different for inhaled loxapine + IM lorazepam and each agent alone over a 12-h postdose period. Although the central nervous system sedative effects were observed for each treatment in healthy volunteers, the effect was greater following concomitant lorazepam 1 mg IM + inhaled loxapine 10 mg administration. There were no deaths, serious AEs, premature discontinuations due to AEs, or treatment-related AEs. PMID:27022468

  20. Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: A placebo-controlled, randomized study

    PubMed Central

    Cloutier, C; Taliano, J; O’Mahony, W; Csanadi, M; Cohen, G; Sutton, I; Sinclair, D; Awde, M; Henein, S; Robinson, L; Eisenhoffer, J; Piraino, PS; Harsanyi, Z; Michalko, KJ

    2013-01-01

    BACKGROUND For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone/CR naloxone. OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain. METHODS: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication. RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per-protocol population. According to per-protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD) pain scores measured on a visual analogue scale (48.6±23.1 mm versus 55.9±25.4 mm; P=0.0296) and five-point ordinal pain intensity scores (2.1±0.8 versus 2.4±0.9; P=0.0415) compared with placebo. After the double-blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six-month, open-label evaluation. CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity. PMID:23662289

  1. Validation of Orthopedic Postoperative Pain Assessment Methods for Dogs: A Prospective, Blinded, Randomized, Placebo-Controlled Study

    PubMed Central

    Rialland, Pascale; Authier, Simon; Guillot, Martin; del Castillo, Jérôme R. E.; Veilleux-Lemieux, Daphnée; Frank, Diane; Gauvin, Dominique; Troncy, Eric

    2012-01-01

    In the context of translational research, there is growing interest in studying surgical orthopedic pain management approaches that are common to humans and dogs. The validity of postoperative pain assessment methods is uncertain with regards to responsiveness and the potential interference of analgesia. The hypothesis was that video analysis (as a reference), electrodermal activity, and two subjective pain scales (VAS and 4A-VET) would detect different levels of pain intensity in dogs after a standardized trochleoplasty procedure. In this prospective, blinded, randomized study, postoperative pain was assessed in 25 healthy dogs during a 48-hour time frame (T). Pain was managed with placebo (Group 1, n = 10), preemptive and multimodal analgesia (Group 2, n = 5), or preemptive analgesia consisting in oral tramadol (Group 3, n = 10). Changes over time among groups were analyzed using generalized estimating equations. Multivariate regression tested the significance of relationships between pain scales and video analysis. Video analysis identified that one orthopedic behavior, namely ‘Walking with full weight bearing’ of the operated leg, decreased more in Group 1 at T24 (indicative of pain), whereas three behaviors indicative of sedation decreased in Group 2 at T24 (all p<0.004). Electrodermal activity was higher in Group 1 than in Groups 2 and 3 until T1 (p<0.0003). The VAS was not responsive. 4A-VET showed divergent results as its orthopedic component (4A-VETleg) detected lower pain in Group 2 until T12 (p<0.0009), but its interactive component (4A-VETbeh) was increased in Group 2 from T12 to T48 (p<0.001). Concurrent validity established that 4A-VETleg scores the painful orthopedic condition accurately and that pain assessment through 4A-VETbeh and VAS was severely biased by the sedative side-effect of the analgesics. Finally, the video analysis offered a concise template for assessment in dogs with acute orthopedic pain. However, subjective pain

  2. A Randomized, Placebo-Controlled Study Investigating the Nicotinic α7 Agonist, RG3487, for Cognitive Deficits in Schizophrenia

    PubMed Central

    Umbricht, Daniel; Keefe, Richard SE; Murray, Stephen; Lowe, David A; Porter, Richard; Garibaldi, George; Santarelli, Luca

    2014-01-01

    Effective treatments for cognitive impairment associated with schizophrenia (CIAS) remain an unmet need. Nicotinic α7 receptor agonists may be effective in CIAS. This 8-week (week 1, inpatient; weeks 2–8, outpatient), double-blind, randomized study used Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) guidelines to investigate the nicotinic α7 partial agonist RG3487 (formerly MEM3454) in CIAS; 215 patients with chronic stable schizophrenia received placebo or RG3487 (5, 15, or 50 mg) added to ongoing treatment with risperidone, paliperidone, or aripiprazole. Primary end point was baseline to week 8 change in MATRICS Consensus Cognitive Battery (MCCB) composite t-score. Secondary outcomes were change in MCCB domain and negative symptom assessment (NSA) scores. The study did not allow for evaluation of nonsmokers. Each RG3487 dose was evaluated using a mixed-effects model repeated measures approach. Mean (SD) baseline MCCB composite t-score was 28.3 (12.0). No significant effect on MCCB composite t-scores was observed with RG3487 (adjusted mean difference (SE) vs placebo: 5 mg: 0.11 (1.39); 15 mg: −1.95 (1.39); 50 mg: −1.13 (1.37); p=0.2–0.9). RG3487 did not improve MCCB domain scores. In a post hoc analysis of patients with moderate negative symptoms, 5 and 50 mg RG3487 vs placebo significantly improved NSA total (−4.45 (p=0.04) and −4.75 (p=0.02), respectively) and global (−0.39 (p=0.04) and −0.55 (p=0.003), respectively) scores. The MCCB did not lead to higher than expected patient withdrawal. RG3487 was generally well tolerated. In patients with stable schizophrenia, RG3487 did not improve cognitive deficits, as assessed by the MCCB; however, in patients with moderate negative symptoms, a post hoc analysis revealed significant improvement of negative symptoms. PMID:24549101

  3. [Felbinac gel for treatment of localized extra-articular rheumatic diseases--a multicenter, placebo controlled, randomized study].

    PubMed

    Bolten, W

    1991-01-01

    281 patients with extra-articular rheumatic disorders (enthesiopathy, bursitis, tendinosis, fibrositis) and moderate or severe localized pain during rest or movement in shoulder, neck, elbow or knee were randomized into groups and treated for 14 days in a double blind study with either 1 g Felbinac Gel 3% (biphenyl acetic acid) three times daily (N = 142) or with the gel formulation only (N = 139). In 50% of the patients treated with Felbinac Gel compared to 29% of the placebo treated patients (p = 0.001), the investigator assessed the global therapeutic success to be good or very good. The magnitude of complaints judged on the basis of a visual analogous scale by patients and doctor showed a significant improvement in pain reduction during rest or activity after 14 days of treatment in the Felbinac group. The rheumatic complaints diminished equally according to patient judgement in both treatment groups and the concomitant use of paracetamol was low in both groups. No significant side-effects or changes in laboratory parameters were observed during therapy. Felbinac Gel therefore is suitable for a low-risk topical therapy of soft tissue rheumatic disorders. PMID:1872042

  4. Memantine for axial signs in Parkinson's disease: a randomised, double-blind, placebo-controlled pilot study

    PubMed Central

    Moreau, Caroline; Delval, Arnaud; Tiffreau, Vincent; Defebvre, Luc; Dujardin, Kathy; Duhamel, Alain; Petyt, Gregory; Hossein-Foucher, Claude; Blum, David; Sablonnière, Bernard; Schraen, Susanna; Allorge, Delphine; Destée, Alain; Bordet, Régis; Devos, David

    2013-01-01

    Background Given that memantine is thought to decrease N-methyl-D-aspartic-acid-related (NMDA) glutamatergic hyperactivity and improve locomotion in rats, we sought to assess the drug's impact on axial symptoms in advanced Parkinson's disease (PD). Methods We performed a 90-day, randomised, double-blind, study with two parallel arms: 20 mg/day memantine versus placebo (ClinicalTrials.gov:NCT01108029). The main inclusion criterion was the presence of a severe gait disorder and an abnormal, forward-leaning stance. The following parameters were analysed under standardised conditions before and after acute administration of L-dopa: gait (stride length as primary criterion), the United-Parkinson's-Disease-Rating-Scale (UPDRS) motor score and its axial subscore, the hypertonia and strength of the axial extensors and flexors (isokinetic dynamometer), the Dyskinesia Rating Scale score (DRS) and its axial subscore. Results Twenty-five patients were included. The memantine and placebo group did not differ significantly in terms of stride length. However, in the memantine group, we observed significantly better results (vs placebo) for the overall UPDRS score (F(1,21)=4.9; p=0.039(−1)) and its axial subscore (F(1,21)=7.2; p=0.014(−1.1)), axial hypertonia, the axial and overall DRS and axial strength. Conclusions Memantine treatment was associated with lower axial motor symptom and dyskinesia scores but did not improve gait. These benefits must be confirmed in a broader population of patients. PMID:23077087

  5. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study.

    PubMed

    Landsberg, G M; Beck, A; Lopez, A; Deniaud, M; Araujo, J A; Milgram, N W

    2015-09-12

    The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across 'during' and 'post' thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity. PMID:26311736

  6. Novel Form of Curcumin Improves Endothelial Function in Young, Healthy Individuals: A Double-Blind Placebo Controlled Study

    PubMed Central

    Stoner, Lee; Rowlands, David S.; Caldwell, Aaron R.; Sanders, Elizabeth; Kreutzer, Andreas; Mitchell, Joel B.; Purpura, Martin; Jäger, Ralf

    2016-01-01

    Curcumin, a turmeric extract, may protect against cardiovascular diseases by enhancing endothelial function. In this randomized controlled double-blind parallel prospective study, fifty-nine healthy adults were assigned to placebo, 50 mg (50 mg), or 200 mg (200 mg) curcumin, for 8 weeks. The higher curcumin (200 mg) supplementation produced a dose-mediated improvement in endothelial function measured by flow-mediated dilation (FMD). The outcome was a clinically substantial 3.0% increase (90% CI 0.7 to 5.3%, p = 0.032; benefit : harm odds ratio 546 : 1) with the 200 mg dose, relative to placebo. The 50 mg dose also increased FMD relative to placebo by 1.7% (−0.6 to 4.0%, p = 0.23; 25 : 1), but the outcome was not clinically decisive. In apparently healthy adults, 8 weeks of 200 mg oral curcumin supplementation resulted in a clinically meaningful improvement in endothelial function as measured by FMD. Oral curcumin supplementation may present a simple lifestyle strategy for decreasing the risk of cardiovascular diseases. This trial was registered at ISRCTN registry (ISRCTN90184217).

  7. Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study

    PubMed Central

    Naber, Marnix; Hommel, Bernhard; Colzato, Lorenza S.

    2015-01-01

    Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate’s diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest that it serves as a cognitive enhancer. As choline is important for the communication between motor neurons and the control of skeletal muscles, we assumed that choline supplementation may have positive effects on action coordination in humans. A group of twenty-eight individuals ingested two grams of choline bitartrate or a placebo in two separate sessions. Seventy minutes post ingestion, participants performed a visuomotor aiming task in which they had to rapidly hit the centers of targets. Results showed that participants hit targets more centrally after choline supplementation. Pupil size (a cognition-sensitive biomarker) also significantly decreased after choline intake and correlated positively with the hit distance to the targets and the number of target misses, and negatively with reaction times. These findings point to a choline-induced bias towards action precision in the trade-off between speed and accuracy. The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system. PMID:26271904

  8. Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study.

    PubMed

    Naber, Marnix; Hommel, Bernhard; Colzato, Lorenza S

    2015-01-01

    Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate's diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest that it serves as a cognitive enhancer. As choline is important for the communication between motor neurons and the control of skeletal muscles, we assumed that choline supplementation may have positive effects on action coordination in humans. A group of twenty-eight individuals ingested two grams of choline bitartrate or a placebo in two separate sessions. Seventy minutes post ingestion, participants performed a visuomotor aiming task in which they had to rapidly hit the centers of targets. Results showed that participants hit targets more centrally after choline supplementation. Pupil size (a cognition-sensitive biomarker) also significantly decreased after choline intake and correlated positively with the hit distance to the targets and the number of target misses, and negatively with reaction times. These findings point to a choline-induced bias towards action precision in the trade-off between speed and accuracy. The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system. PMID:26271904

  9. Antimicrobial effect of adjunctive use of chlorhexidine mouthrinse in untreated gingivitis: a randomized, placebo-controlled study.

    PubMed

    Becerik, Sema; Türkoğlu, Oya; Emingil, Gülnur; Vural, Caner; Ozdemir, Güven; Atilla, Gül

    2011-06-01

    The aim of this study was to examine the effectiveness of chlorhexidine mouthrinse (CHX) in addition to daily plaque control on subgingival microbiota in patients with untreated gingivitis. Fifty gingivitis patients were randomized to CHX or placebo groups. CHX group rinsed with 0.2% CHX, while placebo group rinsed with placebo mouthrinse for 4 weeks. Subgingival plaque samples were collected and plaque index (PI), papilla bleeding index (PBI), calculus index, and probing pocket depth (PPD) were recorded at baseline and at 4 weeks. The amounts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum, and total bacteria were detected by quantitative real-time PCR method. In the CHX group the total bacteria count was significantly reduced in posterior teeth at 4 weeks (p < 0.05), while no significant decrease was observed in the placebo group (p > 0.05). CHX mouthrinse as an adjunct to daily plaque control could be useful in the management of plaque-associated gingivitis and in reducing the subgingival total bacteria count especially in posterior teeth. PMID:21569094

  10. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study

    PubMed Central

    Landsberg, G. M.; Beck, A.; Lopez, A.; Deniaud, M.; Araujo, J. A.; Milgram, N. W.

    2015-01-01

    The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across ‘during’ and ‘post’ thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity. PMID:26311736

  11. The effect of oscillating-energy manual therapy on lateral epicondylitis: a randomized, placebo-control, double-blinded study.

    PubMed

    Nourbakhsh, Mohammad Reza; Fearon, Frank J

    2008-01-01

    Symptoms of lateral epicondylitis (LE) are attributed to degenerative changes and inflammatory reactions in the common extensor tendon induced by microscopic tears in the tissue after repetitive or overload functions of the wrist and hand extensor muscles. Conventional treatments, provided on the premise of inflammatory basis of LE, have shown 39-80% failure rate. An alternative approach suggests that symptoms of LE could be due to active tender points developed in the origin of hand and wrist extensor muscles after overuse or repetitive movements. Oscillating-energy Manual Therapy (OEMT), also known as V-spread, is a craniosacral manual technique that has been clinically used for treating tender points over the suture lines in the skull. Considering symptoms of LE may result from active tender points, the purpose of this study was to investigate the effect of OEMT on pain, grip strength, and functional abilities of subjects with chronic LE. Twenty-three subjects with chronic LE (>3mo) between ages of 24 and 72 years participated in this study. Before their participation, all subjects were screened to rule out cervical and other pathologies that could possibly contribute to their lateral elbow pain. Subjects who met the inclusion criteria were randomized into treatment and placebo treatment groups by a second (treating) therapist. Subjects were blinded to their group assignment. Subjects in the treatment group received OEMT for six sessions. During each treatment session, first a tender point was located through palpation. After proper hand placement, the therapist focused the direction of the oscillating energy on the localized tender point. Subjects in the placebo group underwent the same procedure, but the direction of the oscillating energy was directed to an area above or below the tender points, not covering the affected area. Jamar Dynamometer, Patient Specific Functional Scale (PSFS), and Numeric Rating Scale (NRS) were used to measure grip strength

  12. Evaluation Series on Safety and Efficacy of Nutritional Supplements in Newly Diagnosed Hyperglycemia: A Placebo-Controlled, Randomized Study

    PubMed Central

    Thacker, Hemant; Bantwal, Ganapati; Jain, Sunil; Kalra, Sanjay; Kale, Shailaja; Saboo, Banshi; Gupta, Jugal B.; Sivam, Sakthivel

    2016-01-01

    Background: Diabetes is endemic with developing economies contributing to the bulk of this pandemic. Despite the evidence of incremental benefit of glycemic control starting early in life, acceptance of and adherence to modern medications remain suboptimal. Aims: To determine the hemoglobin A1c (HbA1c)-lowering efficacy and safety of nutritional supplement, PreCrea®, in adult Indians with newly diagnosed hyperglycemia. Materials and Methods: Double-blind, randomized study conducted in six diabetes centers in India. A total of 193 treatment-naïve subjects with newly diagnosed hyperglycemia and fasting plasma glucose (FPG) >100 mg/dL were randomized into either PreCrea® 600 mg (n = 90) or matched placebo (n = 89) capsules twice daily, along with lifestyle modification, for 12 weeks. The main outcomes were changes in HbA1c and FPG levels, attainment of the American Diabetes Association (ADA)-defined goals for HbA1c, and clinical and biochemical measures of safety. Results: At 12 weeks, mean HbA1c in PreCrea® group reduced by 0.91% compared with 0.08% increase in the placebo group (P < .001). The reductions in the mean FPG at week 4 (P < .001) and week 12 (P = 0.04) were significant compared to the baseline. ADA goal of HbA1c <7% increased from 15.5% at the baseline to 35.6% at week 12 in PreCrea® subjects. Clinical safety and biochemical safety did not change. Hypoglycemia and weight gain were not observed with PreCrea®. Conclusions: Nearly 1% point reduction in HbA1c at week 12 with PreCrea® is comparable with most first-line glucose-lowering drugs. The safety and tolerability of PreCrea® highlights its potential as a first-line therapy in newly detected hyperglycemia. PMID:27042609

  13. Does enriched acoustic environment in humans abolish chronic tinnitus clinically and electrophysiologically? A double blind placebo controlled study.

    PubMed

    Vanneste, Sven; van Dongen, Marijn; De Vree, Bjorn; Hiseni, Senad; van der Velden, Eddy; Strydis, Christos; Joos, Kathleen; Norena, Arnaud; Serdijn, Wouter; De Ridder, Dirk

    2013-02-01

    Animal research has shown that loss of normal acoustic stimulation can increase spontaneous firing in the central auditory system and induce cortical map plasticity. Enriched acoustic environment after noise trauma prevents map plasticity and abolishes neural signs of tinnitus. In humans, the tinnitus spectrum overlaps with the area of hearing loss. Based on these findings it can be hypothesized that stimulating the auditory system by presenting music compensating specifically for the hearing loss might also suppress chronic tinnitus. To verify this hypothesis, a study was conducted in three groups of tinnitus patients. One group listened just to unmodified music (i.e. active control group), one group listened to music spectrally tailored to compensate for their hearing loss, and a third group received music tailored to overcompensate for their hearing loss, associated with one (in presbycusis) or two notches (in audiometric dip) at the edge of hearing loss. Our data indicate that applying overcompensation to the hearing loss worsens the patients' tinnitus loudness, the tinnitus annoyance and their depressive feelings. No significant effects were obtained for the control group or for the compensation group. These clinical findings were associated with an increase in current density within the left dorsal anterior cingulate cortex in the alpha2 frequency band and within the left pregenual anterior cingulate cortex in beta1 and beta2 frequency band. In addition, a region of interest analysis also demonstrated an associated increase in gamma band activity in the auditory cortex after overcompensation in comparison to baseline measurements. This was, however, not the case for the control or the compensation groups. In conclusion, music therapy compensating for hearing loss is not beneficial in suppressing tinnitus, and overcompensating hearing loss actually worsens tinnitus, both clinically and electrophysiologically. PMID:23104014

  14. 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

  15. Mirtazapine versus amitriptyline in the long-term treatment of depression: a double-blind placebo-controlled study.

    PubMed

    Montgomery, S A; Reimitz, P E; Zivkov, M

    1998-03-01

    Of 580 patients randomly assigned to short-term, double-blind treatment with either mirtazapine, amitriptyline or placebo, a total of 217 patients clinically judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study (mirtazapine, n = 74; amitriptyline, n = 86 and placebo, n = 57). The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data. Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo (p < 0.05), and a significantly longer time to relapse was shown on the survival analysis. There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks, with fewer patients relapsing. There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis (p < 0.05). The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks. At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response. Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms, but there was no difference from placebo in the proportion of patients with sustained response. Mirtazapine was well tolerated with a side-effect profile similar to that of placebo. The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain. Objectively measured weight gain was more frequent with amitriptyline (22% of patients) compared with mirtazapine (13% of patients). Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo, in particular sedative and anticholinergic side effects. The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression, which on some measures showed an advantage

  16. Randomized, Placebo-Controlled, Crossover Study of Methylphenidate for Attention-Deficit/Hyperactivity Disorder Symptoms in Preschoolers with Developmental Disorders

    PubMed Central

    Aman, Michael G.; Lecavalier, Luc; Riddle, Mark A.; Gelenberg, Alan; Wright, Ron; Rice, Sydney; Ghuman, Harinder S.; Fort, Carolyn

    2009-01-01

    Abstract Objective The aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID). Methods Fourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and “optimal dose” for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD subscale of the Conners' Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD). Results MPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects. Conclusion The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely. PMID:19702485

  17. The effectiveness of low laser therapy in subacromial impingement syndrome: a randomized placebo controlled double‐blind prospective study

    PubMed Central

    Dogan, Sebnem Koldas; AY, Saime; Evcik, Deniz

    2010-01-01

    OBJECTIVES: Conflicting results were reported about the effectiveness of Low level laser therapy on musculoskeletal disorders. The aim of this study was to investigate the effectiveness of 850‐nm gallium arsenide aluminum (Ga‐As‐Al) laser therapy on pain, range of motion and disability in subacromial impingement syndrome. METHODS: A total of 52 patients (33 females and 19 males with a mean age of 53.59±11.34 years) with subacromial impingement syndrome were included. The patients were randomly assigned into two groups. Group I (n = 30, laser group) received laser therapy (5 joule/cm2 at each point over maximum 5‐6 painful points for 1 minute). Group II (n = 22, placebo laser group) received placebo laser therapy. Initially cold pack (10 minutes) was applied to all of the patients. Also patients were given an exercise program including range of motion, stretching and progressive resistive exercises. The therapy program was applied 5 times a week for 14 sessions. Pain severity was assessed by using visual analogue scale. Range of motion was measured by goniometer. Disability was evaluated by using Shoulder Pain and Disability Index. RESULTS: In group I, statistically significant improvements in pain severity, range of motion except internal and external rotation and SPADI scores were observed compared to baseline scores after the therapy (p<0.05). In Group II, all parameters except range of motion of external rotation were improved (p<0.05). However, no significant differences were recorded between the groups (p>0.05). CONCLUSIONS: The Low level laser therapy seems to have no superiority over placebo laser therapy in reducing pain severity, range of motion and functional disability. PMID:21120304

  18. 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

  19. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults.

    PubMed

    McIntyre, Roger S; Lophaven, Søren; Olsen, Christina K

    2014-10-01

    The efficacy of vortioxetine 10 and 20 mg/d vs. placebo on cognitive function and depression in adults with recurrent moderate-to-severe major depressive disorder (MDD) was evaluated. Patients (18-65 yr, N = 602) were randomized (1:1:1) to vortioxetine 10 or 20 mg/d or placebo for 8 wk in a double-blind multi-national study. Cognitive function was assessed with objective neuropsychological tests of executive function, processing speed, attention and learning and memory, and a subjective cognitive measure. The primary outcome measure was change from baseline to week 8 in a composite z-score comprising the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test (RAVLT) scores. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). In the pre-defined primary efficacy analysis, both doses of vortioxetine were significantly better than placebo, with mean treatment differences vs. placebo of 0.36 (vortioxetine 10 mg, p < 0.0001) and 0.33 (vortioxetine 20 mg, p < 0.0001) on the composite cognition score. Significant improvement vs. placebo was observed for vortioxetine on most of the secondary objectives and subjective patient-reported cognitive measures. The differences to placebo in the MADRS total score at week 8 were -4.7 (10 mg: p < 0.0001) and -6.7 (20 mg: p < 0.0001). Path and subgroup analyses indicate that the beneficial effect of vortioxetine on cognition is largely a direct treatment effect. No safety concern emerged with vortioxetine. Vortioxetine significantly improved objective and subjective measures of cognitive function in adults with recurrent MDD and these effects were largely independent of its effect on improving depressive symptoms. PMID:24787143

  20. High-intensity intermittent training in hypoxia: a double-blinded, placebo-controlled field study in youth football players.

    PubMed

    Brocherie, Franck; Girard, Olivier; Faiss, Raphael; Millet, Grégoire P

    2015-01-01

    This study examined the effects of 5 weeks (∼60 minutes per training, 2 d·wk) of run-based high-intensity repeated-sprint ability (RSA) and explosive strength/agility/sprint training in either normobaric hypoxia repeated sprints in hypoxia (RSH; inspired oxygen fraction [FIO2] = 14.3%) or repeated sprints in normoxia (RSN; FIO2 = 21.0%) on physical performance in 16 highly trained, under-18 male footballers. For both RSH (n = 8) and RSN (n = 8) groups, lower-limb explosive power, sprinting (10-40 m) times, maximal aerobic speed, repeated-sprint (10 × 30 m, 30-s rest) and repeated-agility (RA) (6 × 20 m, 30-s rest) abilities were evaluated in normoxia before and after supervised training. Lower-limb explosive power (+6.5 ± 1.9% vs. +5.0 ± 7.6% for RSH and RSN, respectively; both p < 0.001) and performance during maximal sprinting increased (from -6.6 ± 2.2% vs. -4.3 ± 2.6% at 10 m to -1.7 ± 1.7% vs. -1.3 ± 2.3% at 40 m for RSH and RSN, respectively; p values ranging from <0.05 to <0.01) to a similar extent in RSH and RSN. Both groups improved best (-3.0 ± 1.7% vs. -2.3 ± 1.8%; both p ≤ 0.05) and mean (-3.2 ± 1.7%, p < 0.01 vs. -1.9 ± 2.6%, p ≤ 0.05 for RSH and RSN, respectively) repeated-sprint times, whereas sprint decrement did not change. Significant interactions effects (p ≤ 0.05) between condition and time were found for RA ability-related parameters with very likely greater gains (p ≤ 0.05) for RSH than RSN (initial sprint: 4.4 ± 1.9% vs. 2.0 ± 1.7% and cumulated times: 4.3 ± 0.6% vs. 2.4 ± 1.7%). Maximal aerobic speed remained unchanged throughout the protocol. In youth highly trained football players, the addition of 10 repeated-sprint training sessions performed in hypoxia vs. normoxia to their regular football practice over a 5-week in-season period was more efficient at enhancing RA ability (including direction changes), whereas it had no additional effect on improvements in lower-limb explosive power, maximal sprinting, and RSA

  1. Melatonin treatment effects on adolescent students' sleep timing and sleepiness in a placebo-controlled crossover study.

    PubMed

    Eckerberg, Berndt; Lowden, Arne; Nagai, Roberta; Akerstedt, Torbjörn

    2012-11-01

    During the last few decades, the incidence of sleep-onset insomnia, due to delay of circadian phase, has increased substantially among adolescents all over the world. We wanted to investigate whether a small dose of melatonin given daily, administered in the afternoon, could advance the sleep timing in teenagers. Twenty-one students, aged 14-19 yrs, with sleep-onset difficulties during school weeks were recruited. The study was a randomized, double blind, placebo (PL)-controlled crossover trial, lasting 5 wks. During the first 6 d in wks 2 and 4, the students received either PL or melatonin (1 mg) capsules between 16:30 and 18:00 h. During the first 6 d of wk 5, all students received melatonin. Wks 1 and 3 were capsule-free. In the last evening of each week and the following morning, the students produced saliva samples at home for later melatonin analysis. The samples were produced the same time each week, as late as possible in the evening and as early as possible in the morning. Both the student and one parent received automatic mobile text messages 15 min before saliva sampling times and capsule intake at agreed times. Diaries with registration of presumed sleep, subjective sleepiness during the day (Karolinska Sleepiness Scale, KSS) and times for capsule intake and saliva samplings were completed each day. Primary analysis over 5 wks gave significant results for melatonin, sleep and KSS. Post hoc analysis showed that reported sleep-onset times were advanced after melatonin school weeks compared with PL school weeks (p < .005) and that sleep length was longer (p < .05). After the last melatonin school week, the students fell asleep 68 min earlier and slept 62 min longer each night compared with the baseline week. Morning melatonin values in saliva diminished compared with PL (p < .001) and evening values increased (p < .001), indicating a possible sleep phase advance. Compared with PL school weeks, the students reported less wake up (p < .05), less school

  2. Effect of Gaboxadol on Sleep in Adult and Elderly Patients with Primary Insomnia: Results From Two Randomized, Placebo-Controlled, 30-Night Polysomnography Studies

    PubMed Central

    Lankford, D. Alan; Corser, Bruce C.; Zheng, Yan-Ping; Li, Zhengrong; Snavely, Duane B.; Lines, Christopher R.; Deacon, Steve

    2008-01-01

    Study Objectives: To evaluate the efficacy and tolerability of gaboxadol in the treatment of adult and elderly patients with primary insomnia. Design: Randomized, double-blind, placebo-controlled, multicenter, 30-night, polysomnography studies. Setting: Sleep laboratory. Patients: Primary insomnia, 18–64 y (adult study), or ≥65 y (elderly study). Interventions: Adult study: gaboxadol 15 mg (GBX15; N = 148), 10 mg (GBX10; N = 154), or placebo (N = 156); elderly study: GBX10 (N = 157), gaboxadol 5 mg (GBX5; N = 153), or placebo (N=176). Measurements and Results: Primary endpoints were wake after sleep onset (WASO) and latency to persistent sleep (LPS). Slow wave sleep (SWS) was a secondary endpoint. Analyses were based on the change from baseline for the average of nights 1/2, and nights 29/30, and compared gaboxadol versus placebo. Exploratory endpoints included patient's subjective assessment of total sleep time (sTST), WASO (sWASO), time to sleep onset (sTSO), and number of awakenings (sNAW); these analyses were based on weekly means. 1) Adult study. GBX15 significantly (P ≤ 0.05) improved WASO through nights 29/30 but had no significant effects on LPS. No significant differences were seen for GBX10 versus placebo on WASO or LPS. GBX15 and GBX10 enhanced SWS. GBX15 significantly improved sTST, sWASO, sTSO, and sNAW at weeks 1 and 4. 2) Elderly study. GBX10 significantly improved WASO through nights 29/30; a significant improvement was also seen for GBX5 at nights 1/2 but this was not maintained through nights 29/30. GBX10 significantly improved LPS at nights 1/2 but the improvement was not maintained through nights 29/30; no significant differences were seen for GBX5 versus placebo on LPS. GBX10 and GBX5 enhanced SWS. GBX10 significantly improved sTST at week 1, and sTST, sWASO, and sNAW at week 4. Gaboxadol was generally well tolerated in both studies. Conclusions: The maximum studied doses of gaboxadol (GBX15 in adult patients and GBX10 in elderly patients

  3. Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study and Open-Label Extension

    PubMed Central

    Wellman, Charles V.; Israel, Robert J.; Barrett, Andrew C.; Paterson, Craig; Forbes, William P.

    2015-01-01

    Abstract Background: Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); however, fixed-dose administration of MNTX may improve ease of administration. Objective: The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials. Methods: In a double-blind, randomized, placebo-controlled trial (RCT), patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body weight [38 kg to <62 kg or ≥62 kg, respectively]) or placebo every other day (QOD) for two weeks. Patients completing the RCT could enroll in an open-label extension (OLE) study with MNTX administered as needed (PRN). The primary endpoint was percentage of patients with a rescue-free bowel movement (RFBM) within four hours after ≥2 of the first 4 doses in the first week. Results: In the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149 patients continued to the OLE study. The percentage of patients achieving primary endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001). Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001). Efficacy results during the OLE study were consistent with the RCT. MNTX demonstrated a favorable safety profile in the RCT and OLE study. Conclusion: Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness. PMID:25973526

  4. A Randomized Double-Blind Placebo-Controlled Study to Compare Preemptive Analgesic Efficacy of Novel Antiepileptic Agent Lamotrigine in Patients Undergoing Major Surgeries

    PubMed Central

    Shah, Priyank; Bhosale, Uma A; Gupta, Ankush; Yegnanarayan, Radha; Sardesai, Shalini

    2016-01-01

    Background: If postoperative acute pain remains unrelieved, it may result in significant morbidity and mortality. Preemptive analgesic initiated before surgery offers premature analgesia even before exposure to an initial noxious stimulus bestowing effective postoperative analgesia. In developed countries, it is regularly practiced as a part of well-defined protocol. In our country however, only a few centers practice it and that too irregularly and with undefined protocol. Few studies support preemptive analgesic efficacy of novel antiepileptic agent gabapentin. Though lamotrigine is a proven analgesic in animal models of chronic pain and clinical studies of gabapentin-resistant neuropathic pain, a literature search revealed scarce data on its preemptive analgesic efficacy. Aims: The present study is designed to study the preemptive analgesic efficacy of lamotrigine in comparison with diclofenac sodium in postoperative pain control. Materials and Methods: This randomized clinical trial included 90 patients of both sexes, between 18 years and 70 years undergoing major surgeries. Patients were randomly allocated into placebo, control, and test groups and received the respective treatment 30 min before the induction of anesthesia. Aldrete score and pain score were recorded using visual analog scale (VAS), facial rating scale (FRS), and behavioral rating scale (BRS) at awakening and at 1 h, 2 h, 4 h, 6 h, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Results: Significantly higher pain scores were observed in the placebo group postoperatively for 2 h on all pain scales (P < 0.05), whereas in the control group it was significantly higher at 1 h (P < 0.05). The test group patients were more comfortable throughout the study and postoperative analgesic requirement was significantly less (P < 0.05). Conclusions: The study recommends the use of single oral dose lamotrigine as preemptive analgesic for effective postoperative pain control. PMID

  5. The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study.

    PubMed

    Ray, Lara A; Bujarski, Spencer; Courtney, Kelly E; Moallem, Nathasha R; Lunny, Katy; Roche, Daniel; Leventhal, Adam M; Shoptaw, Steve; Heinzerling, Keith; London, Edythe D; Miotto, Karen

    2015-09-01

    Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA. PMID:25801501

  6. Efficacy and Safety of AM-101 in the Treatment of Acute Inner Ear Tinnitus—A Double-Blind, Randomized, Placebo-Controlled Phase II Study

    PubMed Central

    van de Heyning, Paul; Muehlmeier, Guido; Cox, Tony; Lisowska, Grazyna; Maier, Heinz; Morawski, Krzysztof; Meyer, Thomas

    2014-01-01

    Objective To evaluate the efficacy and safety of intratympanic AM-101 in patients with persistent acute inner ear tinnitus after acute acoustic trauma, idiopathic sudden sensorineural hearing loss (ISSNHL), or acute otitis media. Study Design Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 7, 30, and 90. Setting Twenty-eight European sites (academic tertiary referral centers and private ENT practices). Patients 248 patients aged 16 to 65 years. Interventions Three intratympanic injections of AM-101 (0.27 or 0.81 mg/ml) or placebo over 3 consecutive days. Main Outcome Measures Efficacy was assessed by changes in minimum masking level (MML; primary end point), loudness match, tinnitus loudness, tinnitus annoyance, and sleep difficulties on a 0 to 100 numerical rating scale, THI-12 questionnaire, and patient global impression of change. Safety was evaluated using the frequency of clinically relevant hearing deterioration and adverse events. Results The study overall failed to demonstrate a treatment benefit based on the change in MML. However, AM-101 0.81 mg/ml showed statistically significantly better improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media. The subgroup of ISSNHL-related tinnitus patients did not show conclusive results. The study drug and I.T. injections were well tolerated. Conclusion The study established proof of concept for AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Patient-reported outcomes seem to be more relevant and reliable efficacy measures for assessing treatment-related changes in tinnitus than psychoacoustic tests. PMID:24603353

  7. The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials.

    PubMed

    Paloyelis, Y; Krahé, C; Maltezos, S; Williams, S C; Howard, M A; Fotopoulou, A

    2016-04-01

    Oxytocin is a neuropeptide regulating social-affiliative and reproductive behaviour in mammals. Despite robust preclinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin, human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception. In the present study, we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double-blind, placebo-controlled, cross-over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ- and C-fibre nerve endings in the epidermis, at the same time as recording the ensuing laser-evoked potentials (LEPs). We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1, N2 and P2 components. We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 (but not of P2) LEPs, and increased the latency of the N2 component. Importantly, for the first time, the present study reports an association between the analgesic effect of oxytocin (reduction in subjective pain ratings) and the oxytocin-induced modulation of cortical activity after noxious stimulation (attenuation of the N2 LEP). These effects indicate that oxytocin modulates neural processes contributing to pain perception. The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C-fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing. PMID:26660859

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

    PubMed Central

    Pae, Chi-Un; Patkar, Ashwin A.

    2014-01-01

    Objective: The current study investigates whether milnacipran, an equipotent serotonin-norepinephrine reuptake inhibitor, is effective in reducing chronic radicular pain in patients (N = 11) with lumbosacral disc disease. Method: This study is a 10-week randomized, parallel-group, double-blind, placebo-controlled trial of milnacipran (100–200 mg/d, dosed twice a day). Subjects (enrolled from October 2010 to September 2011 through the Duke University Pain and Palliative Care Clinic, Durham, North Carolina) included patients with radiologically confirmed disc disease with nerve root compression. The primary outcome measure was radicular pain measured by visual analog scale score (VAS-Rad); patients were asked to specifically rate radicular pain (“shooting or electrical or prickly pain in 1 or both legs”). Secondary outcome measures included nociceptive low back pain by visual analog scale (VAS-Noc), Oswestry Low Back Pain Disability Questionnaire, Neuropathic Pain Questionnaire, Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey, Beck Depression Inventory, and State-Trait Anxiety Inventory. Between-group changes in outcome measures between baseline and endpoint were analyzed using Mann-Whitney U nonparametric measure of central tendency. Results: Milnacipran treatment yielded statistically significant reduction in radicular pain (VAS-Rad, P = .01) and nociceptive low back pain (VAS-Noc, P = .04) compared to placebo. No statistically significant between-group differences were observed in the other secondary outcome measures. Conclusions: In this small pilot study, milnacipran treatment was associated with reduction in radicular and nociceptive low back pain in patients with lumbosacral disc disease. Larger studies of milnacipran in this population are warranted. Trial Registration: ClinicalTrials.gov identifier: NCT01777581. PMID:25664215

  9. 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

  10. 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

  11. 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

  12. A European multicentre, placebo-controlled supplementation study with alpha-tocopherol, carotene-rich palm oil, lutein or lycopene: analysis of serum responses.

    PubMed

    Olmedilla, Begoña; Granado, Fernando; Southon, Susan; Wright, Anthony J A; Blanco, Inmaculada; Gil-Martinez, Enrique; van den Berg, Henk; Thurnham, David; Corridan, Bernice; Chopra, Mridula; Hininger, Isabelle

    2002-04-01

    Increased levels of oxidative stress have been implicated in tissue damage and the development of chronic diseases, and dietary antioxidants may reduce the risk of oxidative tissue damage. As part of a European multicentre project, several studies were undertaken with the aim of testing whether the consumption of foods rich in carotenoids reduces oxidative damage to human tissue components. We describe here the serum response of carotenoids and tocopherols upon supplementation with carotenoids from natural extracts (alpha-carotene+beta-carotene, lutein or lycopene; 15 mg/day) and/or with alpha-tocopherol (100 mg/day) in a multicentre, placebo-controlled intervention study in 400 healthy male and female volunteers, aged 25-45 years, from five European regions (France, Northern Ireland, Republic of Ireland, The Netherlands and Spain). Supplementation with alpha-tocopherol increased serum alpha-tocopherol levels, while producing a marked decrease in serum gamma-tocopherol. Supplementation with alpha- + beta-carotene (carotene-rich palm oil) resulted in 14-fold and 5-fold increases respectively in serum levels of these carotenoids. Supplementation with lutein (from marigold extracts) elevated serum lutein (approx. 5-fold), zeaxanthin (approx. doubled) and ketocarotenoids (although these were not present in the supplement), whereas lycopene supplementation (from tomato paste) resulted in a 2-fold increase in serum lycopene. The isomer distributions of beta-carotene and lycopene in serum remained constant regardless of the isomer composition in the capsules. In Spanish volunteers, additional data showed that the serum response to carotenoid supplementation reached a plateau after 4 weeks, and no significant side effects (except carotenodermia) or changes in biochemical or haematological indices were observed throughout the study. This part of the study describes dose-time responses, isomer distribution, subject variability and side effects during supplementation with the

  13. Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer's Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study

    PubMed Central

    Gold, Michael; Alderton, Claire; Zvartau-Hind, Marina; Egginton, Sally; Saunders, Ann M.; Irizarry, Michael; Craft, Suzanne; Landreth, Gary; Linnamägi, Ülla; Sawchak, Sharon

    2010-01-01

    Background/Aims A phase II study of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer's disease (AD) detected a treatment benefit to cognition in apolipoprotein E (APOE)-∊4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate AD. An open-label extension study assessed the long-term safety and tolerability of 8 mg RSG XR. Methods This double-blind, randomized, placebo-controlled study enrolled 693 subjects. Within 2 APOE allelic strata (∊4-positive, ∊4-negative), subjects were randomized (2:2:2:1) to once-daily placebo, 2 mg RSG XR, 8 mg RSG XR or 10 mg donepezil (control). Coprimary endpoints were change from baseline to week 24 in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score, and week 24 Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+). Results At week 24, no significant differences from placebo in change from baseline in coprimary endpoints were detected with either the RSG XR dose in APOE-∊4-negative subjects or overall. For donepezil, no significant treatment difference was detected in ADAS-Cog; however, a significant difference was detected (p = 0.009) on the CIBIC+. Peripheral edema was the most common adverse event for 8 mg RSG XR (15%) and placebo (5%), and nasopharyngitis for 2 mg RSG XR (7%). Conclusion No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-∊4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology. PMID:20733306

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

    PubMed Central

    2012-01-01

    Background Prebiotics are food ingredients, usually non-digestible oligosaccharides, that are selectively fermented by populations of beneficial gut bacteria. Endoxylanases, altering the naturally present cereal arabinoxylans, are commonly used in the bread industry to improve dough and bread characteristics. Recently, an in situ method has been developed to produce arabinoxylan-oligosaccharides (AXOS) at high levels in breads through the use of a thermophilic endoxylanase. AXOS have demonstrated potentially prebiotic properties in that they have been observed to lead to beneficial shifts in the microbiota in vitro and in murine, poultry and human studies. Methods A double-blind, placebo controlled human intervention study was undertaken with 40 healthy adult volunteers to assess the impact of consumption of breads with in situ produced AXOS (containing 2.2 g AXOS) compared to non-endoxylanase treated breads. Volatile fatty acid concentrations in faeces were assessed and fluorescence in situ hybridisation was used to assess changes in gut microbial groups. Secretory immunoglobulin A (sIgA) levels in saliva were also measured. Results Consumption of AXOS-enriched breads led to increased faecal butyrate and a trend for reduced iso-valerate and fatty acids associated with protein fermentation. Faecal levels of bifidobacteria increased following initial control breads and remained elevated throughout the study. Lactobacilli levels were elevated following both placebo and AXOS-breads. No changes in salivary secretory IgA levels were observed during the study. Furthermore, no adverse effects on gastrointestinal symptoms were reported during AXOS-bread intake. Conclusions AXOS-breads led to a potentially beneficial shift in fermentation end products and are well tolerated. PMID:22657950

  15. 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

    Benichou, Annie-Claude; Armanet, Marion; Bussière, Anthony; Chevreau, Nathalie; Cardot, Jean-Michel; Tétard, Jan

    2014-11-01

    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

  16. 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

  17. Pharmacologic Modulation of Hand Pain in Osteoarthritis: A Double-Blind Placebo-Controlled Functional Magnetic Resonance Imaging Study Using Naproxen

    PubMed Central

    Sanders, Duncan; Krause, Kristina; O'Muircheartaigh, Jonathan; Thacker, Michael A; Huggins, John P; Vennart, William; Massat, Nathalie J; Choy, Ernest; Williams, Steven C R; Howard, Matthew A

    2015-01-01

    Objective In an attempt to shed light on management of chronic pain conditions, there has long been a desire to complement behavioral measures of pain perception with measures of underlying brain mechanisms. Using functional magnetic resonance imaging (fMRI), we undertook this study to investigate changes in brain activity following the administration of naproxen or placebo in patients with pain related to osteoarthritis (OA) of the carpometacarpal (CMC) joint. Methods A placebo-controlled, double-blind, 2-period crossover study was performed in 19 individuals with painful OA of the CMC joint of the right hand. Following placebo or naproxen treatment periods, a functionally relevant task was performed, and behavioral measures of the pain experience were collected in identical fMRI examinations. Voxelwise and a priori region of interest analyses were performed to detect between-period differences in brain activity. Results Significant reductions in brain activity following treatment with naproxen, compared to placebo, were observed in brain regions commonly associated with pain perception, including the bilateral primary somatosensory cortex, thalamus, and amygdala. Significant relationships between changes in perceived pain intensity and changes in brain activity were also observed in brain regions previously associated with pain intensity. Conclusion This study demonstrates the sensitivity of fMRI to detect the mechanisms underlying treatments of known efficacy. The data illustrate the enticing potential of fMRI as an adjunct to self-report for detecting early signals of efficacy of novel therapies, both pharmacologic and nonpharmacologic, in small numbers of individuals with persistent pain. PMID:25533872

  18. Efficacy of Rivaroxaban for thromboprophylaxis after Knee Arthroscopy (ERIKA). A phase II, multicentre, double-blind, placebo-controlled randomised study.

    PubMed

    Camporese, Giuseppe; Bernardi, Enrico; Noventa, Franco; Bosco, Mario; Monteleone, Giuseppe; Santoro, Luca; Bortoluzzi, Cristiano; Freguja, Stefano; Nardin, Michela; Marullo, Matteo; Zanon, Giacomo; Mazzola, Claudio; Damiani, Guido; Maniscalco, Pietro; Imberti, Davide; Lodigiani, Corrado; Becattini, Cecilia; Tonello, Chiara; Agnelli, Giancarlo

    2016-08-01

    Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nine Italian teaching or community hospitals were allocated to once-daily rivaroxaban (10 mg) or placebo for seven days in a phase II, multicentre, double-blind, placebo-controlled randomised trial. The primary efficacy outcome was a composite of all-cause death, symptomatic thromboembolism and asymptomatic proximal DVT at three months; major bleeding represented the primary safety outcome. All patients underwent whole-leg ultrasonography at day 7(+1), or earlier if symptomatic. A total of 241 patients were randomised (122 rivaroxaban, 119 placebo), and 234 completed the study. The primary efficacy outcome occurred in 1/120 of the rivaroxaban group and in 7/114 of the placebo group (0.8 % vs 6.1 %, respectively, p=0.03; absolute risk difference, -5.3 %, 95 % CI, -11.4 to -0.8; crude relative risk 0.14, 95 % CI, 0.02 to 0.83; number-needed-to-treat=19). No major bleedings were observed. We found no association between different arthroscopic procedures and thrombotic events. Small sample size, high exclusion rate, and low number of anterior cruciate ligament reconstruction procedures are the main limitations of our study. In conclusion, a seven-day course of 10-mg rivaroxaban may be safely employed for thromboprophylaxis after KA. Whether prophylaxis after KA should be given to all patients, or to selected "high-risk" subjects, remains to be determined. A larger trial to verify our preliminary results is warranted. PMID:27075710

  19. Modafinil in the treatment of idiopathic hypersomnia without long sleep time--a randomized, double-blind, placebo-controlled study.

    PubMed

    Mayer, Geert; Benes, Heike; Young, Peter; Bitterlich, Marion; Rodenbeck, Andrea

    2015-02-01

    In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo-controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug-free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep-wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non-significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate. PMID:25196321

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

    PubMed

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

    2007-12-01

    This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated. PMID:17581601

  1. Effect of Salsalate on Insulin Action, Secretion, and Clearance in Nondiabetic, Insulin-Resistant Individuals: A Randomized, Placebo-Controlled Study

    PubMed Central

    Liu, Alice; Ariel, Danit; Abbasi, Fahim; Lamendola, Cindy; Grove, Kaylene; Tomasso, Vanessa; Ochoa, Hector; Reaven, Gerald

    2014-01-01

    OBJECTIVE Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance. RESEARCH DESIGN AND METHODS This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment. RESULTS Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change −7% [95% CI −10 to −14] vs. 1% [−3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (−25% [−34 to −15] vs. −6% [−26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (−23% [−30 to −16] vs. 3% [−10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms. CONCLUSIONS Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion. PMID:24963111

  2. Alendronate Effect on the Prevention of Bone loss in Early Stages of Ankylosing Spondylitis: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

    PubMed Central

    Khabbazi, Alireza; Noshad, Hamid; Gafarzadeh, Sevil; Hajialiloo, Mehrzad; Kolahi, Susan

    2014-01-01

    Background: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease that leads to a progressive ankylosis of vertebras and ossification of paravertebral ligaments. Bone loss and osteoporosis are amongst the important complications of AS, treatment of which is a challenging issue. Objectives: This study aimed to clarify the effect of alendronate on the prevention of bone loss in patients with early AS. Patients and Methods: In a randomized, double-blind, placebo-controlled study, 24 patients with early stages of AS were recruited in Emam Reza Hospital, Tabriz University of Medical Sciences. The diagnostic criteria of early AS were Schober’s index ≥ 5, normal hip joint in pelvic radiography, and absence or rarity of syndesmophytes in spine radiography (Taylor index ≤ 1). The participants were randomly allocated to the treatment and control groups and received 70 mg/week of alendronate and the same dose of placebo, respectively, for 12 months. Before and 12 months after the intervention, bone densitometry was performed from lumbar and pelvic region using the dual-energy X-ray absorptiometry (DEXA) method with Hologic QDR model instrument. Patients, physicians who prescribed the medications and those who interpreted the outcomes, and densitometry technicians were unaware of the assigned medication to each patient. Both groups received supplemental calcium (1000 mg/day) and vitamin D (400 mg/day). Results: After 12 months of treatment, hip and lumbar bone mineral density differences were not statistically significant between study groups (P = 0.061 and P = 0.112, respectively). No case of clinically apparent vertebral and nonvertebral fracture were observed in the treatment and control groups. Conclusions: Our results suggested that applying alendronate was ineffective in preventing bone loss in patients with early stages of AS. PMID:25068053

  3. 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

  4. Effect of low-level laser therapy in the treatment of cochlear tinnitus: a double-blind, placebo-controlled study.

    PubMed

    Dehkordi, Mahboobeh Adami; Einolghozati, Sasan; Ghasemi, Seyyed Mohsen; Abolbashari, Samaneh; Meshkat, Mojtaba; Behzad, Hadi

    2015-01-01

    Many treatments for chronic tinnitus have been attempted, but the condition remains difficult to cure, especially in the case of cochlear tinnitus. We conducted a prospective, double-blind, placebo-controlled study to assess the effect of low-dose laser therapy on chronic cochlear tinnitus. Our study population was made up of 66 patients-33 who received active laser treatment (case group) and 33 who received inactive dummy treatment (control group). Patients in the laser group received 5 mV with a wavelength of 650 nm for 20 minutes a day, 5 days a week, for 4 weeks. The controls followed the same schedule, but they were "treated" with an inactive device. The degree of tinnitus was evaluated before and after treatment in each group in three ways: (1) the Tinnitus Severity Index (TSI), (2) a subjective 10-point self-assessment scale for tinnitus loudness, and (3) the Tinnitus Evaluation Test (TET). At study's end, we found no statistically significant differences between the case and control groups in the number of patients who experienced a reduction in TSI values (p = 0.589) or a reduction in subjective self-assessment scores (p = 0.475). Nor did we find any significant reductions in the loudness (p = 0.665) and frequency (p = 0.396) of tinnitus as determined by the TET. We conclude that 5-mV laser therapy with a wavelength of 650 nm is no better than placebo for improving hearing thresholds overall or for treating tinnitus with regard to age, sex, environmental noise level, and the duration of tinnitus. PMID:25606834

  5. Multicenter, randomized, placebo-controlled, double-blind study of the safety and efficacy of oral delapril in patients with congestive heart failure.

    PubMed

    Circo, A; Platania, F; Mangiameli, S; Putignano, E

    1995-06-16

    A total of 101 patients (67 delapril, 34 placebo) with congestive heart failure, New York Heart Association (NYHA) classes II and III, entered a multicenter, randomized (2:1), double-blind, placebo-controlled study to determine the minimum effective and maximum tolerated doses of delapril. Patients received placebo or increasing doses of delapril. After a 2-week run-in period on placebo, patients were randomly assigned to delapril or placebo. The dose of delapril was 7.5 mg twice daily for 2 weeks, 15 mg twice daily for another 2 weeks, followed by 30 mg twice daily for 4 weeks. The dose was increased only if the patient did not present any symptoms of orthostatic hypotension. If such symptoms developed, the code was broken and an open treatment was continued on the minimum effective dose (delapril group). Patients with symptoms of orthostatic hypotension in the placebo group were withdrawn. At the end of the 8-week treatment, 36 (54.5%) patients in the delapril group completed the study on 30 mg twice daily, 12 (18.2%) on 15 mg twice daily, and 18 (27.3%) on 7.5 mg twice daily. Seven patients on placebo were withdrawn because of insufficient therapeutic response; one patient on delapril was lost to follow-up. There was a significant improvement (p < 0.01) in bicycle ergometric performance involving an increase in the exercise duration and the maximum workload tolerated in those patients completing the study on delapril 30 mg twice daily and those finishing on 15 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7778529

  6. Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer.

    PubMed

    Unger, C; Häring, B; Kruse, A; Thumann, A; Schneider, B; Clemm, C; Weber, B; Clevert, H D; Hockertz, S; Kalousek, M B

    2001-01-01

    The primary aim of this study was to evaluate the toxicity (mucositis, diarrhea and leucopenia) of a therapy with 5-fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, Laves coli extract, Colibiogen inject, cell-free soluble fraction from lysed E. coli, Laves strain) in comparison with 5-FU plus placebo. Secondary endpoints included general toxicity, response rate according to WHO, survival time and quality of life. 164 patients with advanced colorectal cancer were enrolled in this randomised, placebo-controlled, double-blind, multicenter phase III study. The treatment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m2/d 5-FU on five consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 verum, 72 placebo) evaluable for response. The therapy with LC-Extract was well tolerated. Adverse events that occurred during the study were mainly judged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m2/d 5-FU in both treatment groups was very low. After treatment with 750 mg/m2/d 5-FU patients in the placebo-group experienced a higher CTC toxicity than in the LC-Extract groups. Remission rate and survival time showed a slight trend in favour of LC-Extract. These results suggest a positive benefit-risk ratio of the additional application of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU. PMID:11367875

  7. 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

  8. Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk women: A randomized placebo-controlled double-blind study

    PubMed Central

    Azargoon, Azam; Ghorbani, Raheb; Aslebahar, Fereshteh

    2016-01-01

    Background: Preterm birth is the major cause of neonatal mortality and morbidity. Objective: The aim of this study was to evaluate the effect of prophylactic vaginal progesterone on decreasing preterm birth rate and neonatal complications in a high-risk population. Materials and Methods: A randomized, double-blind, placebo-controlled study was performed on 100 high-risk singleton pregnancies. Vaginal suppository progesterone (400 mg) or placebo was administered daily between 16-22 wks to 36 wks of gestation. Progesterone (n=50) and placebo (n=50) groups were compared for incidence of preterm delivery and neonatal complications. Results: The preterm birth rate was 52%. Preterm birth rate before the 37 wks of gestation (68% vs. 36%: RR=1.89, 95% CI: 1.25-2.86) and also before the 34 wks of gestation (42% vs. 18%: RR=2.33, 95% CI: 1.19-4.58) in placebo group was significantly higher than progesterone group. Our study also showed that the administration of vaginal progesterone was associated with a significant reduction in the risk of birth weight ≤2500 gr, the rates of respiratory distress syndrome (RDS) and admission to the Neonatal Intensive Care Unit (NICU) in the progesterone group when compared with the placebo group. However, there was no significant difference between the two groups in terms of neonatal death, days of admission in NICU, intraventricular hemorrhage and necrotizing enterocolitis. Conclusion: Prophylactic vaginal progesterone reduced the rate of preterm delivery, the risk of a birth weight ≤2500 gr, the rates of RDS and admission to NICU in women who were at risk of preterm delivery. PMID:27326415

  9. 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

  10. 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

  11. Safety and Immunogenicity of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in HIV-Infected Adults: A Phase 1/2a Randomized, Placebo-Controlled Study

    PubMed Central

    Berkowitz, Elchonon M.; Moyle, Graeme; Stellbrink, Hans-Jürgen; Schürmann, Dirk; Kegg, Stephen; Stoll, Matthias; El Idrissi, Mohamed; Oostvogels, Lidia; Heineman, Thomas C.; Brockmeyer, Norbert; deJesus, Edwin; Esser, Stefan; Hawkins, Trevor; Lalezari, Jacob; Orkin, Chloe; Schneider, Stefan

    2015-01-01

    Background. Human immunodeficiency virus (HIV)–infected individuals are at increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART) era. Because concerns exist about the use of live-attenuated vaccines in immunocompromised individuals, a subunit vaccine may be an appropriate alternative. Methods. This phase 1/2, randomized, placebo-controlled study evaluated the immunogenicity and safety of an investigational HZ subunit vaccine (HZ/su). Three cohorts of HIV-infected adults aged ≥18 years were enrolled: 94 ART recipients with a CD4+ T-cell count of ≥200 cells/mm3, 14 ART recipients with a CD4+ T-cell count of 50–199 cells/mm3, and 15 ART-naive adults with a CD4+ T-cell count of ≥500 cells/mm3. Subjects received 3 doses of HZ/su (50 µg varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3 doses of saline at months 0, 2, and 6. Results. One month after dose 3, serum anti-gE antibody concentrations and frequencies of gE-specific CD4+ T cells were higher following HZ/su vaccination than after receipt of saline (P < .0001). Median cell-mediated immune responses peaked after dose 2. Humoral and cell-mediated immune responses persisted until the end of the study (month 18). No vaccination-related serious adverse events were reported. No sustained impact on HIV load or CD4+ T-cell count was noted following vaccinations. Conclusions. HZ/su was immunogenic and had a clinically acceptable safety profile in HIV-infected adults. Clinical Trials Registration. NCT01165203. PMID:25371534

  12. Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study.

    PubMed

    Choi, Y D; Park, C W; Jang, J; Kim, S H; Jeon, H Y; Kim, W G; Lee, S J; Chung, W S

    2013-01-01

    Ginseng is beneficial for many aspects of human physiology, including sexual function. In this study, we have evaluated the efficacy and safety of an extract of ginseng berry, which has a ginsenoside profile distinct from other parts of the plant, on sexual function in men with erectile dysfunction. In all, 119 men with mild-to-moderate ED participated in a multicenter, randomized, double-blind, parallel, placebo-controlled clinical study. They were administered 4 tablets of either standardized Korean ginseng berry (SKGB, 350 mg ginseng berry extract per tablet), or placebo, daily, for 8 weeks. Efficacy was assessed with the International Index of Erectile Function (IIEF)-15 and premature ejaculation diagnostic tool (PEDT) at the end of the 4th and 8th week. We observed that the total and each of the individual domain scores of IIEF-15 increased from 40.95 ± 7.05 to 46.19 ± 12.69 significantly in the SKGB by the 8th week (P<0.05). The erectile function domain of IIEF changed slightly from 17.17 ± 2.57 to 18.59 ± 5.99 in the SKGB group by the 8th week (P<0.05). In addition, PEDT scores significantly improved from 9.14 ± 4.57 to 7.97 ± 4.4 and 7.53 ± 4.26 in the SKGB group after 4 and 8 weeks of treatment (P<0.05). Safety markers including hormone and lipid in the blood were assessed at the end of the 4th and 8th week and they remained unchanged. Oral administration of the SKGB extract improved all domains of sexual function. It can be used as an alternative medicine to improve sexual life in men with sexual dysfunction. PMID:23254461

  13. Changes in acral blood flux under local application of ropivacaine and lidocaine with and without an adrenaline additive: a double-blind, randomized, placebo-controlled study.

    PubMed

    Häfner, Hans-Martin; Schmid, Ute; Moehrle, Matthias; Strölin, Anke; Breuninger, Helmut

    2008-01-01

    Vascular effects of local anesthetics are especially important in dermatological surgery. In particular, adequate perfusion must be ensured in order to offset surgical manipulations during surgical interventions at the acra. However, the use of adrenaline additives appears fraught with problems when anesthesia affects the terminal vascular system, particularly during interventions at the fingers, toes, penis, outer ears, and tip of the nose. We studied skin blood flux at the fingerpads via laser Doppler flowmetry over the course of 24 hours in a prospective, double-blind, randomized, placebo-controlled study with 20 vascularly healthy test persons following Oberst's-method anesthetic blocks. In each case, 6 ml ropivacaine (7.5 mg/ml) (A), lidocaine 1% without an additive (B), and lidocaine 1% with an adrenaline additive (1:200,000) (C) was used respectively as a verum. Isotonic saline solution was injected as a placebo (D). Measurements were carried out with the aid of a computer simultaneously at D II and D IV on both hands. Administration of (A) led to increased blood flux (+155.2%); of (B) initially to a decrease of 27%; of (C) to a reduction of 55% which was reversible after 40 minutes and of (D) to no change.(A) resulted in sustained vasodilatation which was still demonstrable after 24 h. (B) had notably less vasodilative effect, although comparison with (D) clearly showed that (B) is indeed vasodilative. (C) resulted in only a passing decrease in perfusion; this was no longer measurable when checked after 6 and 24 h. This transient inadequacy of blood flux also appeared after administration of (D). These tests show that adrenaline additive in local anesthesia does not decrease blood flow more than 55% for a period of 16 min. Following these results an adrenaline additive can be safely used for anesthetic blocks at the acra in healthy persons. PMID:18334782

  14. Comparison of Puff Topography, Toxicant Exposure, and Subjective Effects in Low- and High-Frequency Waterpipe Users: A Double-Blind, Placebo-Control Study

    PubMed Central

    Cobb, Caroline O.; Blank, Melissa D.; Morlett, Alejandra; Shihadeh, Alan; Jaroudi, Ezzat; Karaoghlanian, Nareg; Kilgalen, Barbara; Austin, Janet; Weaver, Michael F.

    2015-01-01

    Introduction: Clinical laboratory work among intermittent and daily waterpipe tobacco smokers has revealed significant risks for tobacco dependence and disease associated with waterpipe tobacco smoking (WTS). No studies have compared these groups directly. This study examined whether WTS frequency was associated with differential puff topography, toxicant exposure, and subjective response using a placebo-control design. Methods: Eighty participants reporting WTS of 2–5 episodes (LOW; n = 63) or ≥20 episodes (HIGH; n = 17) per month for ≥6 months completed 2 double-blind, counterbalanced 2-hr sessions that were preceded by ≥12hr of tobacco abstinence. Sessions differed by product smoked ad libitum for 45+ min: preferred brand/flavor of waterpipe tobacco (active) or a flavor-matched tobacco-free waterpipe product (placebo). Outcomes included puff topography, plasma nicotine, carboxyhemoglobin (COHb), and subjective response. Results: HIGH users had more puffs, shorter inter-puff-intervals, and a higher total puff volume for placebo relative to active, as well as relative to LOW users during placebo. Plasma nicotine concentrations increased when smoking active (but not placebo) with no significant differences between groups at 25min post-product administration. COHb increased significantly during all conditions; the largest increase was for HIGH users when smoking placebo. There was some evidence of higher baseline scores for nicotine/tobacco nicotine abstinence symptomology. Conclusions: Higher frequency waterpipe users may be more sensitive to the effects of waterpipe smoke nicotine content. Among HIGH users, higher baseline nicotine/tobacco abstinence symptoms may indicate greater nicotine dependence. These data support continued surveillance of WTS and development of dependence measures specific to this product. PMID:25257982

  15. OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: a randomized, placebo-controlled cross-over study.

    PubMed

    Bron, Tannetje I; Bijlenga, Denise; Boonstra, A Marije; Breuk, Minda; Pardoen, Willem F H; Beekman, Aartjan T F; Kooij, J J Sandra

    2014-04-01

    Attention-deficit/hyperactivity disorder (ADHD) is linked to impaired executive functioning (EF). This is the first study to objectively investigate the effects of a long-acting methylphenidate on neurocognitive test performance of adults with ADHD. Twenty-two adults with ADHD participated in a 6-weeks study examining the effect of osmotic-release oral system methylphenidate (OROS-mph) on continuous performance tests (CPTs; objective measures), and on the self-reported ADHD rating scale (subjective measure) using a randomized, double-blind, placebo-controlled cross-over design. OROS-mph significantly improved reaction time variability (RTV), commission errors (CE) and d-prime (DP) as compared to baseline (Cohen's d>.50), but did not affect hit reaction time (HRT) or omission errors (OE). Compared to placebo, OROS-mph only significantly influenced RTV on one of two CPTs (p<.050). Linear regression analyses showed predictive ability of more beneficial OROS-mph effects in ADHD patients with higher EF severity (RTV: β=.670, t=2.097, p=.042; omission errors (OE): β=-.098, t=-4.759, p<.001), and with more severe ADHD symptoms (RTV: F=6.363, p=.019; HRT: F=3.914, p=.061). Side effects rates were substantially but non-significantly greater for OROS-mph compared to placebo (77% vs. 46%, p=.063). OROS-mph effects indicated RTV as the most sensitive parameter for measuring both neuropsychological and behavioral deficits in adults with ADHD. These findings suggest RTV as an endophenotypic parameter for ADHD symptomatology, and propose CPTs as an objective method for monitoring methylphenidate titration. PMID:24508533

  16. Fatty acids in ADHD: plasma profiles in a placebo-controlled study of Omega 3/6 fatty acids in children and adolescents.

    PubMed

    Johnson, Mats; Månsson, Jan-Eric; Ostlund, Sven; Fransson, Gunnar; Areskoug, Björn; Hjalmarsson, Kerstin; Landgren, Magnus; Kadesjö, Björn; Gillberg, Christopher

    2012-12-01

    The aim of this study was to assess baseline levels and changes in plasma fatty acid profiles in children and adolescents with ADHD, in a placebo-controlled study with Omega 3/6 supplementation, and to compare with treatment response. Seventy-five children and adolescents aged 8-18 years with DSM-IV ADHD were randomized to 3 months of Omega 3/6 (Equazen eye q) or placebo, followed by 3 months of open phase Omega 3/6 for all. n-3, n-6, n-6/n-3 ratio, EPA and DHA in plasma were measured at baseline, 3 and 6 months. Subjects with more than 25 % reduction in ADHD symptoms were classified as responders. At baseline, no significant differences in mean fatty acid levels were seen across active/placebo groups or responder/non-responder groups. The 0-3 month changes in all parameters were significantly greater in the active group (p < 0.01). Compared to non-responders, the 6-month responders had significantly greater n-3 increase at 3 months and decrease in n-6/n-3 ratio at 3 and 6 months (p < 0.05). Omega 3/6 supplementation had a clear impact on fatty acid composition of plasma phosphatidyl choline in active versus placebo group, and the fatty acid changes appear to be associated with treatment response. The most pronounced and long-lasting changes for treatment responders compared to non-responders were in the n-6/n-3 ratio. PMID:22753087

  17. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study.

    PubMed

    Xu, W-M; Cui, Y-T; Wang, L; Yang, H; Liang, Z-Q; Li, X-M; Zhang, S-L; Qiao, F-Y; Campbell, F; Chang, C-N; Gardner, S; Atkins, M

    2009-02-01

    This randomized, double-blind, placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus (HBV) perinatal transmission in highly viraemic mothers. Mothers were randomized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum. At birth, infants received recombinant HBV vaccine with or without HBIg and were followed until week 52. One hundred and fifty mothers, with a gestational age of 26-30 weeks and serum HBV DNA >1000 MEq/mL (bDNA assay), were treated. A total of 141 infants received immunoprophylaxis at birth. In lamivudine-treated mothers, 56 infants received vaccine + HBIg (lamivudine + vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In placebo-treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine + HBIg). At week 52, in the primary analyses where missing data was counted as failures, infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity (10/56, 18%vs 23/59, 39%; P = 0.014) and in detectable HBV DNA (11/56, 20%vs 27/59, 46%; P = 0.003) compared to infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate the impact of missing data at week 52 resulting from a high dropout rate (13% in the lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg group) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers, but the differences were not statistically significant. No safety concerns were noted in the lamivudine-treated mothers or their infants. Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization. PMID:19175878

  18. 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

  19. Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study

    PubMed Central

    Bauer, M; Berman, S; Stamm, T; Plotkin, M; Adli, M; Pilhatsch, M; London, E D; Hellemann, G S; Whybrow, P C; Schlagenhauf, F

    2016-01-01

    Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of

  20. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: A randomised, double-blind, placebo-controlled study in cannabis users

    PubMed Central

    Hindocha, Chandni; Freeman, Tom P.; Schafer, Grainne; Gardener, Chelsea; Das, Ravi K.; Morgan, Celia J.A.; Curran, H. Valerie

    2015-01-01

    Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8 mg), CBD (16 mg), THC+CBD (8 mg+16 mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces. PMID:25534187

  1. 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

  2. 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

  3. 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

  4. 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

  5. Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study

    PubMed Central

    Karpecki, Paul M.; Majmudar, Parag A.; Nichols, Kelly K.; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P.

    2016-01-01

    Purpose: To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. Methods: SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. Results: The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Conclusions: Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events. PMID:27055211

  6. A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, FIXED-DOSE PHASE III STUDY OF VILAZODONE IN PATIENTS WITH GENERALIZED ANXIETY DISORDER

    PubMed Central

    Gommoll, Carl; Durgam, Suresh; Mathews, Maju; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Thase, Michael E

    2015-01-01

    Background Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 ClinicalTrials.gov) evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). Methods A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. Results The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (–1.80 [–3.26, –0.34]; P = .0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P = .0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Conclusions Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. PMID:25891440

  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. A pilot double-blind randomised placebo-controlled dose–response trial assessing the effects of melatonin on infertility treatment (MIART): study protocol

    PubMed Central

    Fernando, Shavi; Osianlis, Tiki; Vollenhoven, Beverley; Wallace, Euan; Rombauts, Luk

    2014-01-01

    Introduction High levels of oxidative stress can have considerable impact on the outcomes of in vitro fertilisation (IVF). Recent studies have reported that melatonin, a neurohormone secreted from the pineal gland in response to darkness, has significant antioxidative capabilities which may protect against the oxidative stress of infertility treatment on gametes and embryos. Early studies of oral melatonin (3–4 mg/day) in IVF have suggested favourable outcomes. However, most trials were poorly designed and none have addressed the optimum dose of melatonin. We present a proposal for a pilot double-blind randomised placebo-controlled dose–response trial aimed to determine whether oral melatonin supplementation during ovarian stimulation can improve the outcomes of assisted reproductive technology. Methods and analyses We will recruit 160 infertile women into one of four groups: placebo (n=40); melatonin 2 mg twice per day (n=40); melatonin 4 mg twice per day (n=40) and melatonin 8 mg twice per day (n=40). The primary outcome will be clinical pregnancy rate. Secondary clinical outcomes include oocyte number/quality, embryo number/quality and fertilisation rate. We will also measure serum melatonin and the oxidative stress marker, 8-hydroxy-2′-deoxyguanosine at baseline and after treatment and levels of these in follicular fluid at egg pick-up. We will investigate follicular blood flow with Doppler ultrasound, patient sleepiness scores and pregnancy complications, comparing outcomes between groups. This protocol has been designed in accordance with the SPIRIT 2013 Guidelines. Ethics and dissemination Ethical approval has been obtained from Monash Health HREC (Ref: 13402B), Monash University HREC (Ref: CF14/523-2014000181) and Monash Surgical Private Hospital HREC (Ref: 14107). Data analysis, interpretation and conclusions will be presented at national and international conferences and published in peer-reviewed journals. Trial registration number ACTRN

  9. Maternal Deworming Research Study (MADRES) protocol: a double-blind, placebo-controlled randomised trial to determine the effectiveness of deworming in the immediate postpartum period

    PubMed Central

    Mofid, Layla S; Casapía, Martín; Montresor, Antonio; Rahme, Elham; Fraser, William D; Marquis, Grace S; Vercruysse, Jozef; Allen, Lindsay H; Gyorkos, Theresa W

    2015-01-01

    Introduction Soil-transmitted helminth infections are endemic in 114 countries worldwide, and cause the highest burden of disease among all neglected tropical diseases. The WHO includes women of reproductive age as a high-risk group for infection. The primary consequence of infection in this population is anaemia. During lactation, anaemia may contribute to reduced quality and quantity of milk, decreasing the duration of exclusive breastfeeding and lowering the age at weaning. To date, no study has investigated the effects of maternal postpartum deworming on infant or maternal health outcomes. Methods and analysis A single-centre, parallel, double-blind, randomised, placebo-controlled trial will be carried out in Iquitos, Peru, to assess the effectiveness of integrating single-dose 400 mg albendazole into routine maternal postpartum care. A total of 1010 mother-infant pairs will be randomised to either the intervention or control arm, following inhospital delivery and prior to discharge. Participants will be visited in their homes at 1, 6, 12 and 24 months following delivery for outcome ascertainment. The primary outcome is infant mean weight gain between birth and 6 months of age. Secondary outcomes include other infant growth indicators and morbidity, maternal soil-transmitted helminth infection and intensity, anaemia, fatigue, and breastfeeding practices. All statistical analyses will be performed on an intention-to-treat basis. Ethics and dissemination Research ethics board approval has been obtained from the McGill University Health Centre (Canada), the Asociación Civil Impacta Salud y Educación (Peru) and the Instituto Nacional de Salud (Peru). A data safety and monitoring committee is in place to oversee study progression and evaluate adverse events. The results of the analyses will be published in peer-reviewed journals, and presented at national and international conferences. Trial registration number Clinicaltrials.gov: NCT01748929. PMID:26084556

  10. Acute effects of delta-9-tetrahydrocannabinol, cannabidiol and their combination on facial emotion recognition: a randomised, double-blind, placebo-controlled study in cannabis users.

    PubMed

    Hindocha, Chandni; Freeman, Tom P; Schafer, Grainne; Gardener, Chelsea; Das, Ravi K; Morgan, Celia J A; Curran, H Valerie

    2015-03-01

    Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling 'stoned' was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being 'stoned'. CBD did not influence feelings of 'stoned'. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces. PMID:25534187

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

    PubMed

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

    2015-07-01

    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

  12. 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. PMID:27218868

  13. Auricular acupuncture for primary care treatment of low back pain and posterior pelvic pain in pregnancy: study protocol for a multicentre randomised placebo-controlled trial

    PubMed Central

    2014-01-01

    Background About 45% of all pregnant women suffer low back pain and/or pelvic girdle pain (LBPGP). This study seeks to evaluate the effect of auricular acupuncture on LBPGP compared with placebo auricular acupuncture and with standard obstetric care in the field of primary health care. Methods and design This study will be a four-parallel-arm, multicentre, randomised, placebo-controlled trial. A total of 212 pregnant women (24 to 36 weeks’ gestation), aged at least 17 years, with LBPGP, will be randomly assigned to the verum auricular acupuncture plus standard obstetric care group (VAAc), to the non-specific auricular acupuncture plus standard obstetric care group (NSAAc), to the non-specific placebo auricular acupuncture plus standard obstetric care group (PAAc), or the standard obstetric care group (SOC). The VAAc, NSAAc, and PAAc groups will receive treatment at three auricular acupuncture points (specific points for the VAAc group or non-specific ones for the NSAAc and PAAc groups), once a week for 2 weeks; the SOC group will receive only standard obstetric care during the same period. The primary outcome will be the reduction in pain intensity, according to the visual analogue scale (iVAS), at 2 weeks after the start of treatment. The secondary outcomes will be functional status with respect to LBPGP (according to the Roland-Morris disability questionnaire), health-related quality of life (SF12) at 2 weeks after the start of treatment, and iVAS at 12 and 48 weeks postpartum. Discussion This trial will implement a high-quality methodology and may provide evidence for the efficacy, safety, and specificity of auricular acupuncture as a treatment for pregnant women with LBPGP. Trial registration Current Controlled Trials ISRCTN41033073 (date 20/03/2014). PMID:25027493

  14. Sodium bicarbonate supplementation improved MAOD but is not correlated with 200- and 400-m running performances: a double-blind, crossover, and placebo-controlled study.

    PubMed

    Brisola, Gabriel Motta Pinheiro; Miyagi, Willian Eiji; da Silva, Henrique Santos; Zagatto, Alessandro Moura

    2015-09-01

    The aim of the study was to investigate the effects of acute supplementation of sodium bicarbonate (NaHCO3) on maximal accumulated oxygen deficit (MAOD) determined by a single supramaximal effort (MAODALT) in running and the correlation with 200- and 400-m running performances. Fifteen healthy men (age, 23 ± 4 years; maximal oxygen uptake, 50.6 ± 6.1 mL·kg(-1)·min(-1)) underwent a maximal incremental exercise test and 2 supramaximal efforts at 110% of the intensity associated with maximal oxygen uptake, which was carried out after ingesting either 0.3 g·kg(-1) body weight NaHCO3 or a placebo (dextrose) and completing 200- and 400-m performance tests. The study design was double-blind, crossover, and placebo-controlled. Significant differences were found between the NaHCO3 and placebo conditions for MAODALT (p = 0.01) and the qualitative inference for substantial changes showed a very likely positive effect (98%). The lactic anaerobic contribution in the NaHCO3 ingestion condition was significantly higher (p < 0.01) and showed a very likely positive effect (99% chance), similar to that verified for peak blood lactate concentration (p < 0.01). No difference was found for time until exhaustion (p = 0.19) or alactic anaerobic contribution (p = 0.81). No significant correlations were observed between MAODALT and 200- and 400-m running performance tests. Therefore, we can conclude that both MAODALT and the anaerobic lactic metabolism are modified after acute NaHCO3 ingestion, but it is not correlated with running performance. PMID:26300016

  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. Interaction between brivaracetam (100 mg/day) and a combination oral contraceptive: a randomized, double-blind, placebo-controlled study.

    PubMed

    Stockis, Armel; Watanabe, Shikiko; Fauchoux, Nicolas

    2014-03-01

    This randomized, double-blind, placebo-controlled, two-way crossover study aimed to assess the pharmacokinetic interactions between brivaracetam 100 mg/day and a combination oral contraceptive (OC) containing 30 μg ethinylestradiol and 150 μg levonorgestrel. The study was performed in 28 healthy women over five 28-day menstrual cycles: baseline (OC only), two treatment cycles with brivaracetam (50 mg b.i.d.) or placebo coadministered with OC separated by a wash-out cycle (OC only), and a follow-up cycle (OC only). The OC was administered on days 1-21 of each cycle, and brivaracetam or placebo on days 1-28 of the treatment cycles. Pharmacokinetics of ethinylestradiol and levonorgestrel were determined on day 20; brivaracetam morning trough levels on days 20 (with OC) and 29 (without OC) were compared. Cmax (maximum plasma concentration) and AUC (area under the plasma concentration versus time curve) ratios for brivaracetam versus placebo (90% confidence interval [CI]) were 0.96 (0.88-1.04) and 0.90 (0.86-0.95) for ethinylestradiol, and 0.95 (0.91-0.99) and 0.92 (0.88-0.97) for levonorgestrel, within predefined bioequivalence limits (0.80-1.25). Brivaracetam trough levels were similar on days 20 and 29 (ratio 1.08; 90% CI 0.98-1.18). No differences in breakthrough bleeding were seen across the five cycles. It was concluded that there were no interactions between brivaracetam 100 mg/day and the OC. PMID:24512385

  17. NCCTG N10C2 (Alliance) – A Double-Blind, Placebo-Controlled Study of Magnesium Supplements to Reduce Menopausal Hot Flashes

    PubMed Central

    Park, Haeseong; Qin, Rui; Smith, Thomas J.; Atherton, Pamela J.; Barton, Debra L.; Sturtz, Keren; Dakhil, Shaker R.; Anderson, Daniel M.; Flynn, Kathleen; Puttabasavaiah, Suneetha; Le-Lindqwister, Nguyet Anh; Padula, Gilbert D.A.; Loprinzi, Charles L.

    2014-01-01

    Objective Hot flashes (HFs) are a common symptom in breast cancer survivors that can negatively impact quality of life. Preliminary data suggested that magnesium might be an effective, low-cost treatment for HFs with minimal side effects. Methods A four-arm, double-blind, placebo-controlled randomized trial was conducted. Postmenopausal women with a history of breast cancer and bothersome HFs were randomized into treatment groups of 800 or 1200 mg daily magnesium oxide, or corresponding placebo groups in 2:2:(1:1) ratios. HF frequency and scores (number times mean severity) were measured using a validated HF diary. A one-week baseline period preceded initiation of study medication. The primary endpoint was the intra-patient difference in average hot flash score between the baseline and the treatment periods, comparing each magnesium group to the combined placebo groups using a gate-keeping procedure. Results were analyzed using repeated measures and growth curve models on weekly HF score, based on a modified intent-to-treat principle. Results 289 women enrolled between 12/2011 and 03/2013. The study groups were well balanced for baseline characteristics. Mean HF scores, frequencies, and associated changes during the treatment period were similar for each group. An increased incidence of diarrhea and a corresponding lower incidence of constipation were reported in magnesium arms compared to placebo. No statistically significant difference occurred in other toxicities or quality of life measures. Conclusions The results of this trial do not support the use of magnesium oxide for HFs. PMID:25423327

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

    PubMed Central

    2014-01-01

    Background StemSport (SS; StemTech International, Inc. San Clemente, CA) contains a proprietary blend of the botanical Aphanizomenon flos-aquae and several herbal antioxidant and anti-inflammatory substances. SS has been purported to accelerate tissue repair and restore muscle function following resistance exercise. Here, we examine the effects of SS supplementation on strength adaptations resulting from a 12-week resistance training program in healthy young adults. Methods Twenty-four young adults (16 males, 8 females, mean age = 20.5 ± 1.9 years, mass = 70.9 ± 11.9 kg, stature = 176.6 ± 9.9 cm) completed the twelve week training program. The study design was a double-blind, placebo controlled parallel group trial. Subjects either received placebo or StemSport supplement (SS; mg/day) during the training. 1-RM bench press, 1-RM leg press, vertical jump height, balance (star excursion and center of mass excursion), isokinetic strength (elbow and knee flexion/extension) and perception of recovery were measured at baseline and following the 12-week training intervention. Results Resistance training increased 1-RM strength (p < 0.008), vertical jump height (p < 0.03), and isokinetic strength (p < 0.05) in both SS and placebo groups. No significant group-by-time interactions were observed (all p-values >0.10). Conclusions These data suggest that compared to placebo, the SS herbal/botanical supplement did not enhance training induced adaptations to strength, balance, and muscle function above strength training alone. PMID:24910543

  19. 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

  20. Randomized, Double-Blind, Placebo-Controlled Study of Encenicline, an α7 Nicotinic Acetylcholine Receptor Agonist, as a Treatment for Cognitive Impairment in Schizophrenia

    PubMed Central

    Keefe, Richard SE; Meltzer, Herbert A; Dgetluck, Nancy; Gawryl, Maria; Koenig, Gerhard; Moebius, Hans J; Lombardo, Ilise; Hilt, Dana C

    2015-01-01

    Encenicline is a novel, selective α7 nicotinic acetylcholine receptor agonist in development for treating cognitive impairment in schizophrenia and Alzheimer's disease. A phase 2, double-blind, randomized, placebo-controlled, parallel-design, multinational study was conducted. Patients with schizophrenia on chronic stable atypical antipsychotics were randomized to encenicline 0.27 or 0.9 mg once daily or placebo for 12 weeks. The primary efficacy end point was the Overall Cognition Index (OCI) score from the CogState computerized battery. Secondary end points include MATRICS Consensus Cognitive Battery (MCCB) (in US patients), the Schizophrenia Cognition Rating Scale (SCoRS) total score, SCoRS global rating, and Positive and Negative Syndrome Scale (PANSS) total and subscale and cognition factor scores. Of 319 randomized patients, 317 were included in the safety population, and 307 were included in the intent-to-treat population. Notable trends in improvement were demonstrated across all cognition scales. For the OCI score, the LS mean difference for encenicline 0.27 mg vs placebo was significant (Cohen's d=0.257; P=0.034). Mean SCoRS total scores decreased showing improvement in function over time, and the difference was significant for encenicline 0.9 mg vs placebo (P=0.011). Furthermore, the difference between encenicline 0.9 mg and placebo was significant for the PANSS Cognition Impairment Domain (P=0.0098, Cohen's d=0.40) and for the PANSS Negative scale (P=0.028, Cohen's d=0.33). Treatment-emergent adverse events were reported at similar frequencies across all treatment groups (39.0% with placebo, 23.4% with encenicline 0.27 mg, and 33.3% with encenicline 0.9 mg). Overall, encenicline was generally well tolerated and demonstrated clinically meaningful improvements in cognition and function in patients with schizophrenia. PMID:26089183

  1. Enantioselective effects of levodropropizine and dropropizine on psychomotor functions in normal volunteers: a placebo-controlled, double-blind comparative study.

    PubMed

    Gatti, G; Barzaghi, N; Dominijanni, R; Cordaro, C; Perucca, E

    1993-01-01

    Levodropropizine is the l-isomer of dropropizine, a racemic drug widely used as a cough suppressant. Compared with the racemate, levodropropizine retains equal antitussive activity but exhibits considerably lower central nervous system (CNS) depressant effects in animal models. In order to assess whether the same differential pharmacodynamic profile also applies to man, a double-blind placebo-controlled study was carried out to investigate the effects of single oral doses (60 and 120 mg) of levodropropizine and dropropizine on subjective alertness (scored on visual analogue scales), general tolerability and psychomotor function tests (cancellation, tapping, choice reaction times and critical flicker fusion frequency) in ten normal volunteers. Treatments were administered in random sequence at intervals of at least one week, evaluation procedures being carried out at times 0, 1, 2, 3, 4, 6 and 8 h after dosing. Following intake of a 60 mg levodropizine dose, subjective effects and objective estimates of psychomotor function were superimposable to those recorded after placebo. There was a trend for 60 mg dropropizine and 120 mg levodropropizine to produce detrimental effects at occasional evaluations, although the changes associated with these treatments could not be differentiated from placebo on the basis of most subjective scores and psychomotor function tests. Conversely, administration of 120 mg dropropizine was consistently associated with subjective CNS impairment and with reduced performance (compared to baseline) in recognition time, critical flicker fusion thresholds and possibly tapping rate, for up to three hours after dosing. These data are consistent with evidence that racemic dropropizine adversely affects central nervous system function to a greater extent compared with the levo-isomer. PMID:8223138

  2. Effects of creatine monohydrate supplementation on exercise-induced apoptosis in athletes: A randomized, double-blind, and placebo-controlled study

    PubMed Central

    Rahimi, Rahman; Mirzaei, Bahman; Rahmani-Nia, Farhad; Salehi, Zivar

    2015-01-01

    Background: Creatine monohydrate (CrM) has been shown to be beneficial to health due to its antioxidant potential. Strenuous exercise is associated with oxidative stress, which could lead to apoptosis. We investigated the ability of CrM in amelioration of apoptosis induced by incremental aerobic exercise (AE) to exhaustion in young athletes. Materials and Methods: In a placebo-controlled, double-blind, randomized, parallel study, 31 young athletes (age 19.52 ± 2.75 years, body mass 79.24 ± 16.13 kg, height 1.73 ± 6.49 m, body fat 16.37% ± 5.92%) were randomly assigned to CrM (4 × 5 g/day, n = 15) or placebo (PL: 4 × 5 g/day of maltodextrine powder; n = 16) to investigate the effect of 7 days CrM on serum p53 and insulin-like growth factor-1 (IGF-1) concentration after acute incremental AE test to exhaustion. Subjects performed AE before (test 1) and after 7 days of supplementation (test 2). Results: Before supplementation, AE to exhaustion induced a significant increase in serum p53 and IGF-1 concentrations at both CrM and PL groups (P < 0.05). After supplementation, serum p53 concentrations were significantly lower in CrM than PL at post-AE (P < 0.05). There were no differences in IGF-1 concentrations between CrM and PL groups at post-AE (P > 0.05). Conclusion: Our results suggest that supplementation with CrM prevents apoptosis, as measured by decreases in p53 concentration, induced by AE to exhaustion in young athletes. However, CrM had no effect on IGF-1 concentration after AE to exhaustion in young athletes. PMID:26664419

  3. A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome

    PubMed Central

    ROSS, Amanda J.; OCON, Anthony J.; MEDOW, Marvin S.; STEWART, Julian M.

    2014-01-01

    POTS (postural tachycardia syndrome) is a chronic form of OI (orthostatic intolerance). Neuropathic POTS is characterized by decreased adrenergic vasoconstriction, whereas hyperadrenergic POTS exhibits increased adrenergic vasoconstriction. We hypothesized that midodrine, an α1-adrenergic receptor agonist, would increase CVR (calf vascular resistance), decrease Cv (calf venous capacitance) and decrease orthostatic tachycardia in neuropathic POTS, but not alter haemodynamics in hyperadrenergic POTS. A total of 20 POTS patients (12 neuropathic and 8 hyperadrenergic), ages 12–20 years, participated in this randomized placebo-controlled double-blind cross-over study. Of these subjects, 15 were female. POTS subjects received 2 weeks of treatment with midodrine or placebo, with increased dosing from 2.5 to 10 mg three times daily. Following a 7-day drug-washout period, subjects received the cross-over treatment. HR (heart rate), MAP (mean arterial pressure), Q̇calf (calf blood flow) and CVR were measured supine and during 35° HUT (head-up tilt). Cv was measured supine. In neuropathic POTS, midodrine decreased supine HR, Q̇calf, and Cv, while increasing MAP and CVR compared with placebo. During HUT, in neuropathic POTS, midodrine decreased HR, Q̇calf and Cv, while increasing MAP and CVR. In hyperadrenergic POTS, placebo and midodrine both decreased upright HR and increased supine CVR. Placebo also increased supine Cv, compared with midodrine in hyperadrenergic POTS. Therefore midodrine improved postural tachycardia in neuropathic POTS by increasing CVR and decreasing Q̇calf and Cv, whereas these effects were not seen in hyperadrenergic POTS patients who experienced a placebo effect. This suggests that midodrine is probably an effective treatment for neuropathic POTS, but not for hyperadrenergic POTS. PMID:23978222

  4. 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

  5. Attenuating effect of Lactobacillus brevis G101 on the MSG symptom complex in a double-blind, placebo-controlled study

    PubMed Central

    Kim, Dong-Hyun; Choi, Yeji; Park, Sun-Sung; Kim, Se-Young

    2015-01-01

    BACKGROUND/OBJECTIVES Lactobacillus brevis G101 suppresses the absorption of monosodium glutamate (MSG) from the intestine into the blood in mice. Therefore, the attenuating effect of orally administered G101 on monosodium glutamate (MSG) symptom complex was investigated in humans. MATERIALS/METHODS Capsules (300 mg) containing Lactobacillus brevis G101 (1×1010 CFU/individual) or maltodextrin (placebo) was orally administered in 30 respondents with self-recognized monosodium glutamate (MSG) symptom complex for 5 days and the rice with black soybean sauce containing 6 g MSG (RBSM) was ingested 30 min after the final administration. Thereafter, the MSG symptom complex (rated on a 5-point scale: 1, none; 5, strong) was investigated in a double blind placebo controlled study. The intensity of the MSG symptom complex was significantly reduced in respondents of the G101 intake group (2.87 ± 0.73) compared to that in those treated with the placebo (3.63 ± 1.03) (P = 0.0016). Respondents in the placebo group exhibited more of the various major conditions of the MSG symptom complex than in the G101 intake group. Although there was no significant difference in the appearance time of the MSG symptom complex between subjects orally administered G101 and those administered the placebo, its disappearance in < 3 h was observed in 69.9% of subjects in the G101 treatment group and in 38.0% of subjects in the placebo group (P = 0.0841). CONCLUSIONS Oral administration of Lactobacillus brevis G101 may be able to reduce the intensity of the MSG symptom complex. PMID:26634058

  6. Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies.

    PubMed

    Weisler, Richard H; Montgomery, Stuart A; Earley, Willie R; Szamosi, Johan; Lazarus, Arthur

    2012-01-01

    Prospectively planned pooled analysis evaluating the efficacy of quetiapine extended release (XR) monotherapy in major depressive disorder (MDD). Data were pooled from two 6-week, randomized, double-blind, placebo-controlled studies of quetiapine XR in outpatients with MDD. The primary endpoint was Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from randomization at week 6. Other evaluations were MADRS response/remission, Hamilton Rating Scale for Anxiety, and subgroup analyses. A total of 968 patients were randomized to quetiapine XR, 150 mg/day (n=315), 300 mg/day (n=323), or placebo (n=330). The mean MADRS total score reductions from randomization were significant at week 6 with quetiapine XR, 150 mg/day (-14.7; P<0.001) and 300 mg/day (-14.7; P<0.001) versus placebo (-11.1), with significant reductions versus placebo from week 1 onward. Response rates (week 6): 52.7% (P<0.001) quetiapine XR 150 mg/day and 49.5% (P<0.001) quetiapine XR 300 mg/day versus placebo (33.0%). MADRS remission (score≤8; week 6): 23.5% (P=0.208) quetiapine XR 150 mg/day and 28.8% (P<0.01) quetiapine XR 300 mg/day versus placebo (19.4%). Quetiapine XR (both doses) significantly improved eight of 10 MADRS items versus placebo at week 6. The therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as sex, age, or severity of depression. In patients with MDD, quetiapine XR (150 and 300 mg/day) monotherapy reduced depressive symptoms, with significant improvements compared with placebo from week 1 onward. PMID:22027845

  7. A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of α4β2 Agonist ABT-894 in Adults with ADHD

    PubMed Central

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

    2013-01-01

    Dysregulation of the neuronal nicotinic acetylcholine receptor (NNR) system has been implicated in attention-deficit/hyperactivity disorder (ADHD), and nicotinic agonists improve attention across preclinical species and humans. Hence, a randomized, double-blind, placebo-controlled, crossover study was designed to determine the safety and efficacy of a novel α4β2 NNR agonist (ABT-894 (3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane)) in adults with ADHD. Participants (N=243) were randomized to one of four dose regimens of ABT-894 (1, 2, and 4 mg once daily (QD)) or 4 mg twice daily (BID) or the active comparator atomoxetine (40 mg BID) vs placebo for 28 days. Following a 2-week washout period, participants crossed over to the alternative treatment condition (active or placebo) for an additional 28 days. Primary efficacy was based on an investigator-rated Conners' Adult ADHD Rating Scale (CAARS:Inv) Total score at the end of each 4-week treatment period. Additional secondary outcome measures were assessed. A total of 238 patients were assessed for safety end points, 236 patients were included in the intent-to-treat data set, and 196 were included in the completers data set, which was the prespecified, primary data set for efficacy. Both the 4 mg BID ABT-894 and atomoxetine groups demonstrated significant improvement on the primary outcome compared with placebo. Several secondary outcome measures were also significantly improved with 4 mg BID ABT-894. Overall, ABT-894 was well tolerated at all dose levels. These results provide initial proof of concept for the use of α4β2 agonists in the treatment of adults with ADHD. Further investigation of ABT-894, including higher doses, is therefore warranted. PMID:23032073

  8. 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. PMID:21887807

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

    PubMed Central

    Emami, Mohammad Hossein; Talaei, Mohammad; Panahi, Yunes; Saburi, Amin; Ghanei, Mostafa

    2014-01-01

    Background: Gastro-esophageal reflux disease (GERD) is prevalent and related to more severe disease in patients with respiratory problems. We evaluated the effects of antireflux therapy in warfare victims of exposure to Mustard gas with chronic cough. Materials and Methods: This randomized, double-blind, placebo-controlled, cross-over study was conducted on 45 cases of sulfur mustard injury with chronic cough (≥8 weeks) and GERD. Patients were randomized into two groups, receiving either 20 mg twice daily omeprazole-placebo (OP) or matching placebo (placebo-omeprazole [PO]) for 4 months, followed by a 1-month washout period and the alternative treatment for 4 months. Assessments included GERD and cough, quality of life, and pulmonary function using spirometry. Leicester Cough Questionnaire and SF-36 were used for measuring quality of life. Results: Patients in the OP group experienced a more decrease than those in the PO group in severity of Leicester cough scores during the first 4-month of trial. After crossing the groups, the OP group experienced an increase (P = 0.036) and the PO group experienced a nonsignificant decrease (P = 0.104) in the severity of scores. The OP group also experienced improvement in GERD symptoms and quality of life at the end of the trial, but changes in the PO group was not significant. There was no significant change in respiratory function indices in any groups. Conclusion: Long-term treatment with high-dose omeprazole improved GERD as well as cough, and quality of life, but not changed respiratory function indices in sulfur mustard injured cases with respiratory symptoms. PMID:25657745

  10. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients

    PubMed Central

    Besarab, Anatole; Provenzano, Robert; Hertel, Joachim; Zabaneh, Raja; Klaus, Stephen J.; Lee, Tyson; Leong, Robert; Hemmerich, Stefan; Yu, Kin-Hung Peony; Neff, Thomas B.

    2015-01-01

    Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects. Methods NDD-CKD subjects with hemoglobin (Hb) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity. Results Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo. Conclusions Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. Clinical Trials Registration Clintrials.gov #NCT00761657. PMID:26238121

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

    PubMed Central

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

    2015-01-01

    Objectives To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery. Design Meta-analysis. Data sources and study eligibility criteria A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief. Results 12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; p<0.001). The VAS scores at the last follow-up time point (last VAS scores) of the bupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; p<0.001). The number of patients requiring supplementary analgesia was also significantly reduced (RR 0.60; 95% CI 0.39 to 0.93; p=0.02), while there was no significant difference in the time to first analgesic request (WMD 3.46; 95% CI −1.81 to 8.72; p=0.20) or short-term side effects (RR 1.67; 95% CI 0.65 to 4.26; p=0.29). Conclusions The administration of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo. PMID:26078306

  12. Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study

    PubMed Central

    Kastelein, John J.P.; Nissen, Steven E.; Rader, Daniel J.; Hovingh, G. Kees; Wang, Ming-Dauh; Shen, Tong; Krueger, Kathryn A.

    2016-01-01

    Aims The objective of this study was to evaluate the efficacy, safety, and tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with primary hypercholesterolaemia, when added to a background of standard-of-care lipid-lowering therapy, including statins. Methods and results Double-blind, placebo-controlled trial randomized 527 patients with primary hypercholesterolaemia from June 2013 to January 2014 at 61 community and academic centres in North America, Europe, and Japan. Patients were randomized to subcutaneous injections of LY 20, 120, or 300 mg every 4 weeks (Q4W); 100 or 300 mg every 8 weeks (Q8W) alternating with placebo Q4W; or placebo Q4W. The primary endpoint was percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) by beta quantification at Week 16. The mean baseline LDL-C by beta quantification was 136.3 (SD, 45.0)mg/dL. LY3015014 dose-dependently decreased LDL-C, with a maximal reduction of 50.5% with 300 mg LY Q4W and 37.1% with 300 mg LY Q8W compared with a 7.6% increase with placebo maintained at the end of the dosing interval. There were no treatment-related serious adverse events (AEs). The most common AE terms (>10% of any treatment group) reported more frequently with LY compared with placebo were injection site (IS) pain and IS erythema. No liver or muscle safety issues emerged. Conclusions LY3015014 dosed every 4 or 8 weeks, resulted in robust and durable reductions in LDL-C. No clinically relevant safety issues emerged with the administration of LY. The long-term effects on cardiovascular outcomes require further investigation. PMID:26757788

  13. Heat-killed Lactobacillus gasseri can enhance immunity in the elderly in a double-blind, placebo-controlled clinical study.

    PubMed

    Miyazawa, K; Kawase, M; Kubota, A; Yoda, K; Harata, G; Hosoda, M; He, F

    2015-01-01

    This double-blind, placebo-controlled clinical trial was conducted to test whether Lactobacillus gasseri TMC0356 (TMC0356) can modify the immune response in the elderly. Heat-killed TMC0356 or placebo was orally administered to 28 healthy subjects aged 50-70 years old for 4 weeks at a dosage of 1.0×10(9) cfu/day. Peripheral blood mononuclear cells (PBMCs) were collected from the subjects before and after the study completion, together with general health and blood examination records. Isolated PBMCs were examined for the number of T cells, CD8(+)CD28(+) cells, native T cells, B cells, natural killer (NK) cells and the ratios of CD4/CD8 T cells and native/memory T cells. NK cell activation and concanavalin A-induced lymphocyte transformation of the isolated PBMCs were also examined. The number of CD8(+) T cells significantly increased in the subjects after TMC0356 oral administration (P<0.05). Furthermore, the population of CD8(+)CD28(+) T cells and the amount of lymphocyte transformation both significantly decreased in PBMCs from the placebo group (P<0.05). However, such changes were not observed in the subjects exposed to TMC0356. These results suggest that TMC0356 can increase the number of CD8(+) T cells and reduce CD28 expression loss in CD8(+) T cells of the elderly. The effect of TMC0356 on immune responses in the elderly may enhance their natural defence mechanisms against pathogenic infections. PMID:25653155

  14. Transient paradoxical bronchospasm associated with inhalation of the LAMA AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled studies

    PubMed Central

    2014-01-01

    Background AZD9164 has demonstrated potential as an inhaled, long-acting, muscarinic antagonist (LAMA) bronchodilator. However, in patients with COPD, but not in healthy subjects, a transient initial drop in FEV1 was observed following inhalation of nebulised doses of AZD9164 in citrate buffer. Two additional studies were conducted to further assess the safety and tolerability of multiple ascending doses of AZD9164 in 27 white and 18 Japanese healthy subjects and in 4 patients with COPD. In these studies, AZD9164 was inhaled via Turbuhaler™. Methods These were Phase I, randomised, double-blind, placebo-controlled, multiple ascending dose (MAD) studies conducted in Sweden and UK. Healthy subjects (mean age 25.9 yrs) and patients with COPD (mean age 66 yrs, mean post-bronchodilator FEV1 60.1% predicted normal value) were randomised 2:1 to active treatment (400, 1000 or 2800 μg delivered doses of AZD9164) or placebo. Results No safety or tolerability concerns were identified in the healthy subjects at doses up to and including 2800 μg and both studies confirmed the bronchodilator effect of AZD9164. However, the first 3 patients in the COPD cohort who received AZD9164 (1000 μg) experienced a transient fall in FEV1 5 to 15 minutes after inhalation of AZD9164 while the patient receiving placebo did not. The study safety review process then resulted in cessation of further activities on AZD9164. Retrospective analysis showed that two healthy subjects had also had transient falls in FEV1 shortly after inhalation of AZD9164 400 and 2800 μg respectively, although neither reported any related respiratory symptoms or other AEs. Conclusions These results show that transient paradoxical bronchoconstriction can occur in some healthy subjects, in addition to patients with COPD, following inhalation of AZD9164 and that the citrate buffer used in the nebulised formulation cannot have been the only cause of the drop in FEV1 in previous studies. As preclinical data do not

  15. 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

  16. First Administration of the Fc-Attenuated Anti-β Amyloid Antibody GSK933776 to Patients with Mild Alzheimer’s Disease: A Randomized, Placebo-Controlled Study

    PubMed Central

    Andreasen, Niels; Simeoni, Monica; Ostlund, Henrik; Lisjo, Pia I.; Fladby, Tormod; Loercher, Amy E.; Byrne, Gerard J.; Murray, Frances; Scott-Stevens, Paul T.; Wallin, Anders; Zhang, Yinghua Y.; Bronge, Lena H.; Zetterberg, Henrik; Nordberg, Agneta K.; Yeo, Astrid J.; Khan, Shahid A.; Hilpert, Jan; Mistry, Prafull C.

    2015-01-01

    Objective To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the Fc-inactivated anti-β amyloid (Aβ) monoclonal antibody (mAb) GSK933776 in patients with mild Alzheimer’s disease (AD) or mild cognitive impairment (MCI). Methods This was a two-part, single blind, placebo-controlled, first-time-in-human (FTIH) study of single (n = 18) and repeat dose (n = 32) intravenous GSK933776 0.001–6 mg/kg (ClinicalTrials.gov: NCT00459550). Additional safety data from an open-label, uncontrolled, single dose study of intravenous GSK933776 1–6 mg/kg (n = 18) are included (ClinicalTrials.gov: NCT01424436). Results There were no cases of amyloid-related imaging abnormalities-edema (ARIA-E) or –hemorrhage (ARIA-H) after GSK933776 administration in both studies. Three patients across the two studies developed anti-GSK933776 antibodies. Plasma GSK933776 half-life (t1/2) was 10–15 days after repeat dosing. After each of three administrations of GSK933776, plasma levels of total Aβ42 and Aβ increased whereas plasma levels of free Aβ decreased dose dependently; no changes were observed for placebo. For total Aβ42 the peak:trough ratio was ≤2 at doses ≥3 mg/kg; for total Aβ the ratio was ≤2 at 6 mg/kg. CSF concentrations of Aβ showed increases from baseline to week 12 for Aβ X–38 (week 12:baseline ratio: 1.65; 95%CI: 1.38, 1.93) and Aβ X–42 (week 12:baseline ratio: 1.18; 95%CI: 1.06, 1.30) for values pooled across doses. Conclusion In this FTIH study the Fc-inactivated anti-Aβ mAb GSK933776 engaged its target in plasma and CSF without causing brain ARIA-E/H in patients with mild AD or MCI. Trial Registration ClinicalTrials.gov NCT00459550 PMID:25789616

  17. 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

  18. Prevalence and Clinical Impact of IgE-Mediated Food Allergy in School Children With Asthma: A Double-Blind Placebo-Controlled Food Challenge Study

    PubMed Central

    Dynowski, Jarosław; Funkowicz, Marzena; Małachowska, Beata; Wąsowska-Królikowska, Krystyna

    2015-01-01

    Purpose Recent studies indirectly suggest a possible link between food allergy (FA) and asthma. Most of them have evaluated the occurrence of FA in asthmatic children, especially in the first year of life, using questionnaire-based studies or specific IgE (sIgE) assay. The aim of this study was to evaluate the prevalence and clinical impact of IgE-mediated FA in school children with asthma using a double-blind placebo-controlled food challenge (DBPCFC). Methods The study group consisted of school children with atopic asthma who were admitted to the Department of Pediatric Allergology, Gastroenterology and Nutrition, Medical University of Lodz, for the evaluation of food hypersensitivity. The diagnosis of FA was established using questionnaires, sIgE analysis, and the DBPCFC. Asthma severity and asthma control state were also assessed. Results A relationship between consumed food and complaints was reported in 180 children (49.7%). Seventy children (19.3%) were sensitized to food allergens. IgE-mediated FA was confirmed in 24 children (6.6%), while 11 children (3%) demonstrated respiratory symptoms. Food-induced asthma exacerbations were observed in 9 patients (2.5%). Statistically significant differences in the prevalence of atopic dermatitis (P<0.002), urticaria (P<0.03), digestive symptoms (P<0.03), rhinitis (P<0.02), sIgE level (P<0.001), positive family history of atopy (P<0.001) and FA in history (P<0.001) were found between asthmatic children with FA and those without. Children with food-induced asthma exacerbations demonstrated significantly greater severity, poorer controls, and worse morbidity compared to those without. Conclusions Although food-induced respiratory reactions in children with asthma were rare, they were classified as severe and associated with worse morbidity, greater severity, and poorer control. As the most commonly observed symptoms were coughing and rhinitis, which can be easily misdiagnosed, a proper diagnosis is essential for

  19. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study.

    PubMed

    Park, Sang-Ki; Jung, In-Chul; Lee, Won Kyung; Lee, Young Sun; Park, Hyoung Kook; Go, Hyo Jin; Kim, Kiseong; Lim, Nam Kyoo; Hong, Jin Tae; Ly, Sun Yung; Rho, Seok Seon

    2011-04-01

    A combination of green tea extract and l-theanine (LGNC-07) has been reported to have beneficial effects on cognition in animal studies. In this randomized, double-blind, placebo-controlled study, the effect of LGNC-07 on memory and attention in subjects with mild cognitive impairment (MCI) was investigated. Ninety-one MCI subjects whose Mini Mental State Examination-K (MMSE-K) scores were between 21 and 26 and who were in either stage 2 or 3 on the Global Deterioration Scale were enrolled in this study. The treatment group (13 men, 32 women; 57.58 ± 9.45 years) took 1,680 mg of LGNC-07, and the placebo group (12 men, 34 women; 56.28 ± 9.92 years) received an equivalent amount of maltodextrin and lactose for 16 weeks. Neuropsychological tests (Rey-Kim memory test and Stroop color-word test) and electroencephalography were conducted to evaluate the effect of LGNC-07 on memory and attention. Further analyses were stratified by baseline severity to evaluate treatment response on the degree of impairment (MMSE-K 21-23 and 24-26). LGNC-07 led to improvements in memory by marginally increasing delayed recognition in the Rey-Kim memory test (P = .0572). Stratified analyses showed that LGNC-07 improved memory and selective attention by significantly increasing the Rey-Kim memory quotient and word reading in the subjects with MMSE-K scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Electroencephalograms were recorded in 24 randomly selected subjects hourly for 3 hours in eye-open, eye-closed, and reading states after a single dose of LGNC-07 (LGNC-07, n = 12; placebo, n = 12). Brain theta waves, an indicator of cognitive alertness, were increased significantly in the temporal, frontal, parietal, and occipital areas after 3 hours in the eye-open and reading states. Therefore, this study suggests that LGNC-07 has potential as an intervention for cognitive improvement. PMID:21303262

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

    PubMed Central

    2013-01-01

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

  1. Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Lee, Juyoun; Choi, Byong Hee; Oh, Eungseok; Sohn, Eun Hee

    2016-01-01

    Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. This study explored the effect of rTMS combined with cognitive training (rTMS-COG) on patients with Alzheimer's disease (AD). Methods A prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca's and Wernicke's areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment. Results Data from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language. Conclusions The present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which

  2. A randomized, double-blind, placebo-controlled, Phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup

    PubMed Central

    Kawai, Akira; Araki, Nobuhito; Hiraga, Hiroaki; Sugiura, Hideshi; Matsumine, Akihiko; Ozaki, Toshifumi; Ueda, Takafumi; Ishii, Takeshi; Esaki, Taito; Machida, Michiko; Fukasawa, Nobuaki

    2016-01-01

    Objective This analysis of the Japanese subpopulation of the PALETTE Phase III, randomized, placebo-controlled study investigated efficacy and safety of pazopanib in patients with metastatic soft tissue sarcoma after failure of standard chemotherapy. Methods Patients were randomly assigned in a 2:1 ratio to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Primary endpoint was progression-free survival. Secondary endpoints included overall survival and overall response rate. Efficacy analysis was by intent-to-treat. Safety was also investigated. Results Forty-seven patients received either pazopanib (n = 31) or placebo (n = 16). Median progression-free survival was 7.0 weeks (95% confidence interval: 4.0–11.7) for placebo and 24.7 weeks (95% confidence interval: 8.6–28.1) for pazopanib (hazard ratio = 0.41 [95% confidence interval: 0.19–0.90]; P = 0.002). Median overall survival was 14.9 months (95% confidence interval: 6.8—not calculable) for placebo and 15.4 months (95% confidence interval: 7.9–28.8) for pazopanib (hazard ratio = 0.87 [95% confidence interval: 0.41–1.83]; P = 0.687). More patients receiving pazopanib experienced best response of stable disease versus placebo. Adverse events were similar to the global population; those leading to dose reduction were more common and mean daily dose was lower in the Japanese population versus the global population (45 vs. 32% and 624.4 vs. 700.4 mg, respectively). Conclusions The efficacy and safety of pazopanib observed in the Japanese subpopulation of PALETTE were similar to those in the global population. Pazopanib is a new treatment option for Japanese patients with metastatic non-adipocytic soft tissue sarcoma after chemotherapy. Clinical trial Registration number NCT00753688; GSK study ID: VEG110727; http://www.gsk-clinicalstudyregister.com/study/VEG110727#ps. PMID:26864131

  3. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies

    PubMed Central

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-01-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5–20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5–20mg/day) was 4.5–7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5–20mg/day) were nausea (20.9–31.2%) and vomiting (2.9–6.5%). For vortioxetine (5–20mg/day), the incidence of TEAEs associated with insomnia was 2.0–5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6–1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7–0.8kg. Thus, vortioxetine (5–20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. PMID:26864543

  4. 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

  5. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

    PubMed

    Baldwin, David S; Chrones, Lambros; Florea, Ioana; Nielsen, Rebecca; Nomikos, George G; Palo, William; Reines, Elin

    2016-03-01

    The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (⩽52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ⩾5% and >2 × placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. PMID:26864543

  6. 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

  7. Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic on H1 Antihistamines: A Randomized, Placebo-Controlled Study

    PubMed Central

    Saini, Sarbjit S; Bindslev-Jensen, Carsten; Maurer, Marcus; Grob, Jean-Jacques; Bülbül Baskan, Emel; Bradley, Mary S; Canvin, Janice; Rahmaoui, Abdelkader; Georgiou, Panayiotis; Alpan, Oral; Spector, Sheldon; Rosén, Karin

    2015-01-01

    ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3% P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8% P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients

  8. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study.

    PubMed

    Saini, Sarbjit S; Bindslev-Jensen, Carsten; Maurer, Marcus; Grob, Jean-Jacques; Bülbül Baskan, Emel; Bradley, Mary S; Canvin, Janice; Rahmaoui, Abdelkader; Georgiou, Panayiotis; Alpan, Oral; Spector, Sheldon; Rosén, Karin

    2015-01-01

    ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12-75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): -4.71 to -1.21; P=0.0010), 2.95 points (95% CI: -4.72 to -1.18; P=0.0012), and 5.80 points (95% CI: -7.49 to -4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3%; P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8%; P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained

  9. The effect of HMB supplementation on body composition, fitness, hormonal and inflammatory mediators in elite adolescent volleyball players: a prospective randomized, double-blind, placebo-controlled study.

    PubMed

    Portal, Shawn; Zadik, Zvi; Rabinowitz, Jonathan; Pilz-Burstein, Ruty; Adler-Portal, Dana; Meckel, Yoav; Cooper, Dan M; Eliakim, Alon; Nemet, Dan

    2011-09-01

    The use of ergogenic nutritional supplements is becoming inseparable from competitive sports. β-Hydroxy-β-Methylbutyric acid (HMB) has recently been suggested to promote fat-free mass (FFM) and strength gains during resistance training in adults. In this prospective randomized, double-blind, placebo-controlled study, we studied the effect of HMB (3 g/day) supplementation on body composition, muscle strength, anaerobic and aerobic capacity, anabolic/catabolic hormones and inflammatory mediators in elite, national team level adolescent volleyball players (13.5-18 years, 14 males, 14 females, Tanner stage 4-5) during the first 7 weeks of the training season. HMB led to a significant greater increase in FFM by skinfold thickness (56.4 ± 10.2 to 56.3 ± 8.6 vs. 59.3 ± 11.3 to 61.6 ± 11.3 kg in the control and HMB group, respectively, p < 0.001). HMB led to a significant greater increase in both dominant and non-dominant knee flexion isokinetic force/FFM, measured at fast (180°/sec) and slow (60°/sec) angle speeds, but had no significant effect on knee extension and elbow flexion and extension. HMB led to a significant greater increase in peak and mean anaerobic power determined by the Wingate anaerobic test (peak power: 15.5 ± 1.6 to 16.2 ± 1.2 vs. 15.4 ± 1.6 to 17.2 ± 1.2 watts/FFM, mean power: 10.6 ± 0.9 to 10.8 ± 1.1 vs. 10.7 ± 0.8 to 11.8 ± 1.0 watts/FFM in control and HMB group, respectively, p < 0.01), with no effect on fatigue index. HMB had no significant effect on aerobic fitness or on anabolic (growth hormone, IGF-I, testosterone), catabolic (cortisol) and inflammatory mediators (IL-6 and IL-1 receptor antagonist). HMB supplementation was associated with greater increases in muscle mass, muscle strength and anaerobic properties with no effect on aerobic capacity suggesting some advantage for its use in elite adolescent volleyball players during the initial phases of the training season. These effects were not accompanied by hormonal and

  10. 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

  11. Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women – PREFER a Randomized, Placebo-Controlled Study

    PubMed Central

    Favrat, Bernard; Balck, Katharina; Breymann, Christian; Hedenus, Michael; Keller, Thomas; Mezzacasa, Anna; Gasche, Christoph

    2014-01-01

    Background Unexplained fatigue is often left untreated or treated with antidepressants. This randomized, placebo-controlled, single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic, unexplained fatigue. Methods Fatigued women (Piper Fatigue Scale [PFS] score ≥5) with iron deficiency (ferritin <50 µg/L and transferrin saturation <20%, or ferritin <15 µg/L) and normal or borderline hemoglobin (≥115 g/L) were enrolled in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study drug and randomized (computer-generated randomization sequence) to a single FCM (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion of patients with reduced fatigue (≥1 point decrease in PFS score from baseline to Day 56). Results The full analysis included 290 women (FCM 144, placebo 146). Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68, 95%CI 1.05–2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3% FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated patients had hemoglobin levels ≥120 g/L (vs. 87% at baseline); with placebo, the proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the cognitive function scores improved better with FCM. ‘Power of attention’ improved better in FCM-treated patients with ferritin <15 µg/L. Treatment-emergent adverse events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia and nausea) were mainly mild or moderate. Conclusion A single infusion of FCM improved fatigue, mental quality-of-life, cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin. Although more side effects were reported compared to placebo, FCM can be an effective alternative in patients who cannot tolerate or use oral iron, the common treatment of iron deficiency

  12. Fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH): study protocol for a randomized, double-blind, placebo-controlled, multicenter trial

    PubMed Central

    2013-01-01

    Background Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is a subtype of stroke that causes a great amount of disability and economic and social burden. This is particularly true in developing countries where it accounts for between 20% and 50% of all strokes. Pharmacological and surgical interventions have been attempted to reduce the mortality and disability caused by ICH, with unsuccessful results. Recently, the use of fluoxetine in addition to physical rehabilitation has been proven useful to improve motor recovery following cerebral infarct. The purpose of this study is to test whether a 3-month treatment with fluoxetine enhances motor recovery in nondepressed patients with acute intracerebral hemorrhage. Methods/design Our study is a randomized, double-blind, placebo-controlled, multicenter clinical trial. We will recruit 86 patients with intracerebral hemorrhage of both sexes, aged >18 years, from four Mexican hospitals. The patients will receive either 20 mg of fluoxetine or a placebo once daily for 90 days. The primary outcome is the mean change in the Fugl-Meyer Motor Scale score between inclusion (day 0) and day 90. The secondary outcomes will be changes in the Barthel Index, the Modified Rankin scale and the National Institutes of Health stroke scale. The outcomes will be measured at day 42 ± 7days and at day 90, for a total of four visits with each subject (at screening and at 0, 42 and 90 days). Discussion Current guidelines recommend early supported hospital discharge and home-based rehabilitation programs as the only cost-effective intervention to aid the recovery of patients with intracerebral hemorrhage. Nevertheless, such interventions are dependent on available resources and funding, which make them very difficult to implement in developing countries. We believe that the identification of a helpful pharmacological intervention to aid the motor recovery of these patients will constitute a breakthrough that will have a major impact in

  13. 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

  14. Adjuvant therapy with minocycline for schizophrenia (The MINOS Trial): study protocol for a double-blind randomized placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Schizophrenia is understood to be a heterogeneous brain condition with overlapping symptom dimensions. The negative symptom dimension, with its protean cognitive manifestations, responds poorly to treatment, which can be a particular challenge in countries where clozapine therapy is not available. Preliminary data indicate that minocycline may be beneficial adjunct in the treatment of schizophrenia: positive, negative, and cognitive symptoms. In this study we aim to assess the efficacy of adjunctive minocycline to alleviate symptoms of schizophrenia in patients who have failed to respond to a therapeutic trial of antipsychotic medications. Methods The study is a parallel group, double-blind, randomized, placebo-controlled trial. Participants will be adults (aged 18 years and above) with first episode or relapse episode of schizophrenia of under 5 years’ duration. Patients who failed to show adequate therapeutic response to at least one antipsychotic medication given for a minimum of 4 weeks will be recruited from a psychiatry hospital in Addis Ababa and a psychiatry clinic in Butajira, Ethiopia. A total of 150 participants (75 in each arm) will be required to detect a five-point mean difference between the intervention arms adjusting for baseline symptom severity, at 90% power and 95% confidence. Patients in the intervention arm will receive minocycline (200 mg/day orally) added on to the regular antipsychotic medications participants are already on. Those in the placebo arm will receive an inactive compound identical in physical appearance to minocycline. Intervention will be offered for 12 weeks. Diagnosis will be established using the operational criteria for research (OPCRIT). Primary outcome measure will be a change in symptom severity measured using the positive and the negative syndrome scale for schizophrenia (PANSS). Secondary outcome measures will include changes in severity of negative symptoms, proportion achieving remission, and level

  15. A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder.

    PubMed

    Sambunaris, Angelo; Bose, Anjana; Gommoll, Carl P; Chen, Changzheng; Greenberg, William M; Sheehan, David V

    2014-02-01

    Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (-3.095 [-5.256, -0.935]; P = 0.0051) and the SDS total score (-2.632 [-4.193, -1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥ 5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales, reflecting symptomatic

  16. A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 28-Day, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

    PubMed Central

    Furey, Sandy A.; Hull, Steven G.; Leibowitz, Mark T.; Jayawardena, Shyamalie; Roth, Thomas

    2014-01-01

    Study Objective: To evaluate multiple doses of gabapentin 250 mg on polysomnography (PSG) and participant-reported sleep assessments in a 5-h phase advance insomnia model. Methods: Adults reporting occasional disturbed sleep received gabapentin 250 mg (n = 128) or placebo (n = 128). On Days 1 and 28, participants received medication 30 min before bedtime and were in bed from 17:00 to 01:00, ∼5 h before their habitual bedtime. Sleep was assessed by PSG, a post sleep questionnaire, and the Karolinska Sleep Diary. Next-day residual effects and tolerability were evaluated. On Days 2-27, participants took medication at home 30 min before their habitual bedtime. Results: Treatment-group demographics were comparable. Gabapentin resulted in significantly less PSG wake after sleep onset (WASO) compared with placebo on Day 1 (primary endpoint, mean: 107.0 versus 149.1 min, p ≤ 0.001) and Day 28 (113.6 versus 152.3 min, p = 0.002), and significantly greater total sleep time (TST; Day 1: 347.6 versus 283.9 min; Day 28: 335.3 versus 289.1 min) (p ≤ 0.001). Participant-reported WASO and TST also showed significant treatment effects on both days. Gabapentin was associated with less %stage1 on Day 1, and greater %REM on Day 28, versus placebo. During home use, gabapentin resulted in significantly less participant-reported WASO and higher ratings of sleep quality. Gabapentin was well tolerated (most common adverse events: headache, somnolence) with no evidence of next-day impairment. Conclusion: Gabapentin 250 mg resulted in greater PSG and participant-reported sleep duration following a 5-h phase advance on Day 1 and Day 28 of use without evidence of next-day impairment, and greater sleep duration during at-home use. Citation: Furey SA, Hull SG, Leibowitz MT, Jayawardena S, Roth T. A randomized, double-blind, placebo-controlled, multicenter, 28-day, polysomnographic study of gabapentin in transient insomnia induced by sleep phase advance. J Clin Sleep Med 2014

  17. Oral nutritional supplement fortified with beta-alanine improves physical working capacity in older adults: a randomized, placebo-controlled study.

    PubMed

    McCormack, William P; Stout, Jeffrey R; Emerson, Nadia S; Scanlon, Tyler C; Warren, Ashlee M; Wells, Adam J; Gonzalez, Adam M; Mangine, Gerald T; Robinson, Edward H; Fragala, Maren S; Hoffman, Jay R

    2013-09-01

    This study examined the effects of an oral nutritional supplement fortified with two different doses of beta-alanine on body composition, muscle function and physical capacity in older adults. Using a double-blind placebo controlled design, 60 men and women (age ± SD = 70.7 ± 6.2 yrs) were randomly assigned to one of three treatment groups: 1) oral nutritional supplement (ONS; n = 20) (8 oz; 230 kcal; 12 g PRO; 31 g CHO; 6 g FAT), 2) ONS plus 800 mg beta-alanine (ONS800; n = 19), and 3) ONS plus 1200 mg beta-alanine (ONS1200; n = 21). Treatments were consumed twice per day for 12 weeks. At pre- and post-supplementation period, participants performed a discontinuous, submaximal cycle ergometry test to determine physical working capacity at fatigue threshold (PWCFT). Fat mass, total body and arm lean soft tissue mass (ALSTM) were measured with DEXA while muscle strength was assessed with handgrip dynamometry (GRIP) and 30-s sit-to-stand (STS) was used to measure lower body functionality. Muscle quality (MQ) was calculated with GRIPmax and DEXA derived ALSTM [GRIP (kg)·ALSTM (kg)(-1)]. Two-way analysis of variance was used to compare pre- to post-supplementation measures and group differences. There were 16 dropouts over the duration of the study. Final group sizes were ONS = 16 (m = 11, w = 5), ONS800 = 15 (m = 5, w = 10), and ONS1200 = 13 (m = 6, w = 7). No significant changes were observed for body composition or GRIP values pre to post. Significant increases in PW(CFT) were seen in ONS1200 (13.6%) and ONS800 (17.8%) pre- to post-supplementation (p < 0.05). These changes were significantly greater (p < 0.05) than the changes in ONS (-6.3%). ONS1200 and ONS had significant increases in STS (22.2 and 10.7%, respectively). While ONS significantly increased in STS, no differences (p > 0.05) in change scores were found between ONS and ONS800. ONS fortified with beta-alanine may improve physical working capacity, muscle quality and function in older men and women

  18. A Phase III, Double-Blind, Placebo-Controlled, Flexible-Dose Study of Levomilnacipran Extended-Release in Patients With Major Depressive Disorder

    PubMed Central

    Bose, Anjana; Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Sheehan, David V.

    2014-01-01

    Abstract Levomilnacipran (1S, 2R-milnacipran) is a potent and selective serotonin and norepinephrine reuptake inhibitor; an extended-release (ER) formulation allows for once-daily dosing. This phase III study (NCT01034462) evaluated the efficacy, the safety, and the tolerability of 40 to 120 mg/d of levomilnacipran ER versus placebo in the treatment of patients (18-80 y) with major depressive disorder. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study comprised a 1-week single-blind, placebo run-in period; an 8-week double-blind treatment; and a 2-week double-blind down-taper period. The primary efficacy parameter was total score change from baseline to week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS); the secondary efficacy was the Sheehan Disability Scale. Analysis was performed using the mixed-effects model for repeated measures on a modified intent-to-treat population. A total of 434 patients received at least 1 dose of double-blind treatment (safety population); 429 patients also had 1 or more postbaseline MADRS assessments (modified intent-to-treat population). The least squares mean differences and 95% confidence interval were statistically significant in favor of levomilnacipran ER versus placebo for the MADRS total score (−3.095 [−5.256, −0.935]; P = 0.0051) and the SDS total score (−2.632 [−4.193, −1.070]; P = 0.0010) change from baseline to week 8. Adverse events were reported in 61.8% of the placebo patients and in 81.6% of the levomilnacipran ER patients. Frequently reported adverse events (≥5% in levomilnacipran ER and twice the rate of placebo) were nausea, dizziness, constipation, tachycardia, urinary hesitation, hyperhidrosis, insomnia, vomiting, hypertension, and ejaculation disorder. In conclusion, there was a statistically significant difference in the score change from baseline to week 8 between levomilnacipran ER and placebo on several depression rating scales

  19. 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

  20. Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn’s disease: Results from a randomised double-blind placebo-controlled study

    PubMed Central

    Raftery, Tara; Martineau, Adrian R; Greiller, Claire L; Ghosh, Subrata; McNamara, Deirdre; Bennett, Kathleen; Meddings, Jon

    2015-01-01

    Background Vitamin D (vitD) supplementation may prolong remission in Crohn’s disease (CD); however, the clinical efficacy and mechanisms are unclear. Aim To determine changes in intestinal permeability (IP), antimicrobial peptide (AMP) concentrations and disease markers in CD, in response to vitD supplementation. Methods In a double-blind randomised placebo-controlled study, we assigned 27 CD patients in remission to 2000 IU/day vitD or placebo for 3 mos. We determined IP, plasma cathelicidin (LL-37 in ng/mL), human-beta-defensin-2 (hBD2 in pg/mL), disease activity (Crohn’s Disease Activity Index (CDAI)), C-reactive protein (CRP in mg/L), fecal calprotectin (µg/g), Quality of Life (QoL) and serum 25-hydroxyvitamin D (25(OH)D in nmol/L) at 0 and 3 mos. Results At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra-group analysis showed increased LL-37 concentrations (p = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p = 0.018) and gastro-duodenal permeability (p = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D ≥ 75 nmol/L had significantly lower CRP (p = 0.019), higher QoL (p = 0.037), higher LL-37 concentrations (p < 0.001) and non-significantly lower CDAI scores (p = 0.082), compared to those with levels <75 nmol/L. Conclusion Short-term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL-37 concentrations and maintenance of IP. Achieving 25(OH)D ≥ 75 nmol/l was accompanied by higher circulating LL-37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388). PMID:26137304

  1. The key role of Shenyan Kangfu tablets, a Chinese patent medicine for diabetic nephropathy: study protocol for a randomized, double-blind and placebo-controlled clinical trial

    PubMed Central

    2013-01-01

    Background Diabetic nephropathy (DN) is a major microvascular complication with diabetes. In China, an estimated 34.7 percent of people diagnosed with diabetes have renal complications and a further 50 percent die of renal failure. Hence, identification of alternative treatments for these patients should be given priority. The Shenyan Kangfu tablet (SYKFT) is a new formulation of an existing and widely acclaimed Chinese herbal tea for treating qi-yin deficiency syndrome. Because a considerable portion of DN patients presenting with symptoms of swelling, fatigue and weak limbs would be diagnosed with qi-yin deficiency syndrome according to the traditional Chinese medicine (TCM) diagnostic criteria, we hypothesize that SYKFT may represent a complementary drug for DN patients with the corresponding syndrome. In view of this, we have designed a trial to assess the efficacy and safety of SYKFT for patients with diabetic nephropathy exhibiting signs of qi and yin deficiency. Methods This is a multicenter, double-blind, randomized controlled trial (RCT). The total target sample size is planned at 80 participants, with a balanced (1:1) treatment allocation. The experimental intervention will be SYKFY plus irbesartan (SI regimen) and the control intervention will be a placebo plus irbesartan (PI regimen). Participants will receive two courses of medication treatment each lasting 8 weeks. The primary outcome will be the composite of the quantitative 24-hour urinary protein level and urinary albumin excretion rate (UAER). Changes in urine albumin-to-creatinine ratio (UACR) and DN staging, and TCM symptom improvement will be the secondary outcome measures. Adverse events (AEs) will be monitored throughout the trial. Discussion This study will be the first placebo-controlled RCT to assess whether SYKFT plus irbesartan will have beneficial effects on enhancing overall response rate (ORR), changing DN staging, improving clinical symptoms, and reducing the frequency of AEs for DN

  2. Safety and immunogenicity of an adjuvanted protein therapeutic HIV-1 vaccine in subjects with HIV-1 infection: a randomised placebo-controlled study.

    PubMed

    Harrer, Thomas; Plettenberg, Andreas; Arastéh, Keikawus; Van Lunzen, Jan; Fätkenheuer, Gerd; Jaeger, Hans; Janssens, Michel; Burny, Wivine; Collard, Alix; Roman, François; Loeliger, Alfred; Koutsoukos, Marguerite; Bourguignon, Patricia; Lavreys, Ludo; Voss, Gerald

    2014-05-01

    The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4(+) T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4(+) and CD8(+) T-cell responses, absolute CD4(+) T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4(+) T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (p<0.05). Vaccine-induced HIV-1-specific CD4(+) T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8(+) T-cells or change in CD8(+) T-cell activation marker expression profile was detected. Absolute CD4(+) T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4(+) T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4(+) T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection. PMID:24144472

  3. Treatment of Post-mastectomy Pain With Ambulatory Continuous Paravertebral Nerve Blocks: A Randomized, Triple-Masked, Placebo-Controlled Study

    PubMed Central

    Ilfeld, Brian M.; Madison, Sarah J.; Suresh, Preetham J.; Sandhu, NavParkash S.; Kormylo, Nicholas J.; Malhotra, Nisha; Loland, Vanessa J.; Wallace, Mark S.; Proudfoot, James A.; Morgan, Anya C.; Wen, Cindy H.; Wallace, Anne M.

    2013-01-01

    Background We aimed to determine with this randomized, triple-masked, placebo-controlled study if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine paravertebral nerve block to a single-injection ropivacaine paravertebral block following mastectomy. Methods Preoperatively, 60 subjects undergoing unilateral (n = 24) or bilateral (n = 36) mastectomy received either unilateral or bilateral paravertebral perineural catheter(s), respectively, inserted between the third and fourth thoracic transverse process(es). All subjects received an initial bolus of ropivacaine 0.5% (15 mL) via the catheter(s). Subjects were randomized to receive either perineural ropivacaine 0.4% or normal saline using portable infusion pump(s) [5 mL/h basal; 300 mL reservoir(s)]. Subjects remained hospitalized for at least 1 night and were subsequently discharged home where the catheter(s) were removed on postoperative day 3. Subjects were contacted by telephone on postoperative days 1, 4, 8, and 28. The primary end point was average pain (scale: 0–10) queried on postoperative day (POD) 1. Results Average pain queried on POD 1 for subjects receiving perineural ropivacaine (n=30) was a median (interquartile) of 2 (0–3), compared with 4 (1–5) for subjects receiving saline (n = 30; 95% CI difference in medians, −4.0 – −0.3; P = 0.021]. During this same time period, subjects receiving ropivacaine experienced a lower severity of breakthrough pain (5 [3–6] vs 7 [5–8]; P = 0.046) as well. As a result, subjects receiving perineural ropivacaine experienced less pain-induced physical and emotional dysfunction, as measured with the Brief Pain Inventory (lower score = less dysfunction): 14 (4–37) vs 57 (8–67) for subjects receiving perineural saline (P = 0.012). For the subscale that measures the degree of interference of pain on 7 domains, such as general activity and relationships, subjects receiving perineural saline reported a median score 10 times

  4. CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial

    PubMed Central

    2012-01-01

    Background Worldwide, over 10 million people are killed or hospitalized because of traumatic brain injury each year. About 90% of deaths occur in low- and middle-income countries. The condition mostly affects young adults, and many experience long lasting or permanent disability. The social and economic burden is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. It has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients. Methods/design The CRASH-3 trial is an international, multicenter, pragmatic, randomized, double-blind, placebo-controlled trial to quantify the effects of the early administration of TXA on death and disability in patients with traumatic brain injury. Ten thousand adult patients who fulfil the eligibility criteria will be randomized to receive TXA or placebo. Adults with traumatic brain injury, who are within 8 h of injury and have any intracranial bleeding on computerized tomography (CT scan) or Glasgow Coma Score (GCS) of 12 or less can be included if the responsible doctor is substantially uncertain as to whether or not to use TXA in this patient. Patients with significant extracranial bleeding will be excluded since there is evidence that TXA improves outcome in these patients. Treatment will entail a 1 g loading dose followed by a 1 g maintenance dose over 8 h. The main analyses will be on an ‘intention-to-treat’ basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time from injury to randomization, the severity of the injury, location of the bleeding, and baseline risk. Interaction tests

  5. History of Depressive and Anxiety Disorders and Paroxetine Response in Patients With Irritable Bowel Syndrome: Post Hoc Analysis From a Placebo-Controlled Study

    PubMed Central

    Marks, David M.; Han, Changsu; Krulewicz, Stan; Pae, Chi-Un; Peindl, Kathleen; Patkar, Ashwin A.; Masand, Prakash S.

    2008-01-01

    Objective: Although irritable bowel syndrome (IBS) is highly comorbid with depressive and anxiety disorders, information on the clinical implications of this comorbidity is limited. We investigated whether a history of depressive and/or anxiety disorders was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in IBS. Method: Seventy-two IBS subjects (diagnosed using Rome II criteria) were recruited from August 2003 to November 2005 and randomly assigned to receive flexibly dosed paroxetine CR (dose, 12.5–50 mg/day) or placebo for 12 weeks. The Mini-International Neuropsychiatric Interview (MINI-Plus version) was used to ascertain current (exclusionary) or past diagnoses of depressive and anxiety disorders. Subjective depression, anxiety, and stress were assessed at entry and throughout the trial using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Perceived Stress Scale (PSS). Severity of IBS symptoms was determined by the Composite Pain Score (CPS), administered via Interactive Voice Response System, and the Clinical Global Impressions scale (CGI). The primary outcome was treatment response defined as ≥ 25% reduction in CPS from randomization to end of treatment. A post hoc analysis (multivariate logistic regression) was done to evaluate whether a history of depressive and/or anxiety disorder was associated with response to medication. Results: Baseline demographic and clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were similar between groups (history of depressive/anxiety disorder vs. no history). In multivariate logistic regression analysis, treatment response was not predicted by history of depressive and/or anxiety disorder (OR = 0.58, CI = 0.29 to 1.68, p = .32) or drug status (paroxetine CR vs. placebo) (OR = 1.26, CI = 0.68 to 3.21, p = .19). Drug status was significantly associated with the secondary outcome variable of treatment response

  6. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study.

    PubMed

    O'Neil, Patrick M; Smith, Steven R; Weissman, Neil J; Fidler, Meredith C; Sanchez, Matilde; Zhang, Jinkun; Raether, Brian; Anderson, Christen M; Shanahan, William R

    2012-07-01

    The BLOOM-DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) study evaluated efficacy and safety of lorcaserin for weight loss in patients with type 2 diabetes. Secondary objectives included evaluations of glycemic control, lipids, blood pressure, and quality of life. This 1-year, randomized, placebo-controlled trial enrolled 604 patients 1:1:1 to placebo, lorcaserin 10 mg once daily (QD) or lorcaserin 10 mg twice daily (BID). Patients were treated with metformin, a sulfonylurea (SFU) or both; had glycated hemoglobin (HbA(1c)) 7-10%; were 18-65 years old; and had BMI 27-45 kg/m(2). Patients received diet and exercise counseling. Safety monitoring included serial echocardiograms. Mean (± SD) age was 52.7 ± 8.7; 54.2% were women; 60.5% were white, 20.9% were African American, and 13.8% were Hispanic. Mean (± SD) weight was 103.6 ± 17.8 kg; BMI was 36.0 ± 4.5 kg/m(2). Most patients (91.7%) took metformin; 50.2% took a SFU. More patients lost ≥5% body weight with lorcaserin BID (37.5%; P < 0.001) or lorcaserin QD (44.7%; P < 0.001) vs. placebo (16.1%; modified intent to treat (MITT)/last observation carried forward (LOCF)). Least square mean (± SEM) weight change was -4.5 ± 0.35% with lorcaserin BID and -5.0 ± 0.5% with lorcaserin QD vs. -1.5 ± 0.36% with placebo (P < 0.001 for each). HbA(1c) decreased 0.9 ± 0.06 with lorcaserin BID, 1.0 ± 0.09 with lorcaserin QD, and 0.4 ± 0.06 with placebo (P < 0.001 for each); fasting glucose decreased 27.4 ± 2.5 mg/dl, -28.4 ± 3.8 mg/dl, and 11.9 ± 2.5 mg/dl, respectively (P < 0.001 for each). Symptomatic hypoglycemia occurred in 7.4% of patients on lorcaserin BID, 10.5% on lorcaserin QD, and 6.3% on placebo. Common adverse events were headache, back pain, nasopharyngitis, and nausea. Lorcaserin was associated with significant weight loss and improvement in glycemic control in patients with type 2 diabetes. PMID:22421927

  7. Testing Public Anxiety Treatments against a Credible Placebo Control

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  8. 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

  9. A Double-Blind, Placebo-Controlled Study of Repetitive Transnasal Sphenopalatine Ganglion Blockade With Tx360® as Acute Treatment for Chronic Migraine

    PubMed Central

    Cady, Roger; Saper, Joel; Dexter, Kent; Manley, Heather R

    2015-01-01

    Objective To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360® are superior in reducing pain associated with chronic migraine (CM) compared with saline. Background The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve. From an anatomical and physiological perspective, SPG blockade may be an effective acute and preventative treatment for CM. Method This was a double-blind, parallel-arm, placebo-controlled, randomized pilot study using a novel intervention for acute treatment in CM. Up to 41 subjects could be enrolled at 2 headache specialty clinics in the US. Eligible subjects were between 18 and 80 years of age and had a history of CM defined by the second edition of the International Classification of Headache Disorders appendix definition. They were allowed a stable dose of migraine preventive medications that was maintained throughout the study. Following a 28-day baseline period, subjects were randomized by computer-generated lists of 2:1 to receive 0.5% bupivacaine or saline, respectively. The primary end-point was to compare numeric rating scale scores at pretreatment baseline vs 15 minutes, 30 minutes, and 24 hours postprocedure for all 12 treatments. SPG blockade was accomplished with the Tx360®, which allows a small flexible soft plastic tube that is advanced below the middle turbinate just past the pterygopalatine fossa into the intranasal space. A 0.3 cc of anesthetic or saline was injected into the mucosa covering the SPG. The procedure is performed similarly in each nostril. The active phase of the study consisted of a series of 12 SPG blocks with 0.3 cc of 0.5% bupivacaine or saline provided 2 times per week for 6 weeks. Subjects were re-evaluated at 1 and 6 months postfinal procedure. Results The final dataset

  10. Comparison of the effects of ketamine or lidocaine on fentanyl-induced cough in patients undergoing surgery: A prospective, double-blind, randomized, placebo-controlled study

    PubMed Central

    Guler, Gülen; Aksu, Recep; Bicer, Cihangir; Tosun, Zeynep; Boyaci, Adem

    2010-01-01

    Background: Fentanyl-induced cough is common but has not been viewed as a serious anesthetic problem. However, the cough may be explosive at times, may require immediate intervention, and may be associated with undesirable increases in intracranial, intraocular, and intra-abdominal pressures. Prevention of fentanylinduced cough in such situations is of paramount importance. Ketamine, at concentrations achieved with standard clinical doses, has a direct relaxant effect on airway smooth muscle. Objective: This study was designed to assess the effects of ketamine or lidocaine on fentanyl-induced cough. Methods: This double-blind, randomized, placebo-controlled study was conducted at the Erciyes University Medical School, Kayseri, Turkey. Consecutive adult patients aged 18 to 65 years and classified as American Society of Anesthesiologists physical status I or II who were undergoing elective surgery with general anesthesia were enrolled. Patients were randomly allocated equally into 3 groups to receive lidocaine 1 mg/kg, ketamine 0.5 μg/kg, or placebo intravenously 1 minute before fentanyl administration. Following intravenous fentanyl (1.5 μg/kg over 2 seconds) injection, an observer, unaware of the type of medication given to the patients, recorded the number of episodes of coughing, if any. Any episode of cough was classified as coughing and graded by investigators blinded to treatment as mild (1–2 coughs), moderate (3–4), or severe (≥5). Blood pressure, heart rate, pulse oximetry oxygen saturation (SpO2), and adverse effects (AEs) were recorded. Results: A total of 368 patients were approached for inclusion; 300 patients met the inclusion criteria and were enrolled in the study. No patients in the ketamine group had cough. The frequency of cough was significantly lower in the lidocaine (11/100 [11%]; P = 0.024) and ketamine (0/100; P = 0.001) groups compared with the placebo group (23/100 [23%]). The intensity of cough was significantly lower in the

  11. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial

    PubMed Central

    Henderson, Samuel T; Vogel, Janet L; Barr, Linda J; Garvin, Fiona; Jones, Julie J; Costantini, Lauren C

    2009-01-01

    Background Alzheimer's disease (AD) is characterized by early and region-specific declines in cerebral glucose metabolism. Ketone bodies are produced by the body during glucose deprivation and are metabolized by the brain. An oral ketogenic compound, AC-1202, was tested in subjects with probable AD to examine if ketosis could improve cognitive performance. Methods Daily administration of AC-1202 was evaluated in 152 subjects diagnosed with mild to moderate AD in a US-based, 90-day, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were on a normal diet and continued taking approved AD medications. Primary cognitive end points were mean change from Baseline in the AD Assessment Scale-Cognitive subscale (ADAS-Cog), and global scores in the AD Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC). AC-1202 was compared to Placebo in several population groups, including: intention-to-treat (ITT), per protocol, and dosage compliant groups. Results were also stratified by APOE4 carriage status (a predefined analysis based on the epsilon 4 (E4) variant of the apolipoprotein E gene). This trial was registered with ClinicalTrials.gov, registry number NCT00142805, information available at Results AC-1202 significantly elevated a serum ketone body (β-hydroxybutyrate) 2 hours after administration when compared to Placebo. In each of the population groups, a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45: 1.9 point difference, p = 0.0235 in ITT; 2.53 point difference, p = 0.0324 in per protocol; 2.6 point difference, p = 0.0215 in dosage compliant. Among participants who did not carry the APOE4 allele (E4(-)), a significant difference was found between AC-1202 and Placebo in mean change from Baseline in ADAS-Cog score on Day 45 and Day 90. In the ITT population, E4(-) participants (N = 55) administered AC-1202 had a significant 4.77 point difference in mean change

  12. Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study

    PubMed Central

    Al-Dujaili, Emad A. S.; Munir, Nimrah; Iniesta, Raquel Revuelta

    2016-01-01

    Background and objectives: Evidence suggests associations between vitamin D deficiency and cardiovascular disease (CVD) risk factors, including hypertension and excessive cortisol levels. Also, vitamin D levels may impact exercise performance. Thus, we aimed to investigate the effects of vitamin D intake on cardiovascular risk factors, free urinary cortisol and exercise performance. Methods: A randomized placebo-controlled single-blinded parallel trial was conducted in healthy participants (n = 15). They received 2000 IU (50 µg) vitamin D3 per day (n = 9) or placebo (lactose) (n = 6) for 14 days. Body composition, systolic blood pressure (SBP), diastolic blood pressure (DBP) and arterial elasticity (as measured by pulse wave velocity, PWV) were recorded at baseline, day 7 and day 14 of intervention. A total of two 24-hour urine samples were collected to estimate free cortisol and cortisone levels. Exercise performance was assessed at the baseline and day 14 of the intervention using a bike ergometer in which BP and PWV were measured before and after exercise. The distance cycled in 20 minutes and the Borg Scale rate of perceived exertion (RPE) were recorded. Results: In the intervention arm, at day 14, vitamin D supplementation significantly reduced SBP and DBP from 115.8 ± 17.1 and 75.4 ± 10.3 at baseline to 106.3 ± 10.9 (p = 0.022) and 68.5 ± 10.1 mmHg (p = 0.012) respectively. Also arterial stiffness was markedly reduced in the vitamin D group (from 7.45 ± 1.55 to 6.11 ± 1.89, p = 0.049). Urinary free cortisol levels and cortisol/cortisone ratio were significantly reduced from 162.65 ± 58.9 nmol/day and 2.22 ± 0.7 to 96.4 ± 37.2 (p = 0.029) and 1.04 ± 0.4 (p = 0.017) respectively. Exercise-induced SBP and DBP were significantly reduced post vitamin D intake from 130.7 ± 12.2 to 116.1 ± 8.1 (p = 0.012) and from 76.2 ± 8.4 to 70.5 ± 7.7 mmHg (p = 0.042) respectively. The distance cycled in 20 minutes significantly increased from 4.98 ± 2.65 to 6

  13. 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

  14. 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

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

    PubMed Central

    2013-01-01

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

  16. A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of pycnogenol for improving allergic rhinitis symptoms.

    PubMed

    Wilson, Dale; Evans, Malkanthi; Guthrie, Najla; Sharma, Prachi; Baisley, Joshua; Schonlau, Frank; Burki, Carolina

    2010-08-01

    The potential of Pycnogenol for relieving allergic rhinitis (birch pollen) symptoms was explored in a double-blind, placebo-controlled trial. In 2008 19 subjects started treatment 3 weeks prior to the onset of birch pollen season in Ontario, Canada. While there was an improvement of eye and nasal symptoms with Pycnogenol, there was no significance versus placebo. It was postulated that Pycnogenol may require a lag-time between the start of therapy and the onset of action. Therefore 39 subjects were treated 5-8 weeks prior to the 2009 birch allergy season. The evaluation of subjects in 2009 showed much lower scores for eye (-35%) and nasal (-20.5%) symptoms with Pycnogenol compared with placebo. In succession of the allergy season birch specific IgE increased by 31.9% in the placebo group compared with only 19.4% in the Pycnogenol group. Detailed analysis suggested that symptom-relief was better the longer subjects were on Pycnogenol prior to the allergen exposure. The best results were found with subjects who took Pycnogenol 7-8 weeks ahead of the allergy season. With the limited number of 39 patients statistical predications were unattainable. In conclusion, Pycnogenol improved allergic rhinitis symptoms when supplementation was started at least 5 weeks before the onset of the allergy season. PMID:20549654

  17. Effect of topical application of methylsulfonylmethane (MSM), EDTA on pitting edema and oxidative stress in a double blind, placebo-controlled study.

    PubMed

    Tripathi, R; Gupta, S; Rai, S; Mittal, P C

    2011-01-01

    No pharmacological treatment exists for lower extremity pitting edema, characterized by inflammation, found in chronic venous insufficiency. Treatment with EDTA, an effective metal chelator, was explored because it can modulate free calcium and iron and prevent further free radical production. However, EDTA may not effectively penetrate the cell membrane, hence methylsulfonylmethane(MSM), reported to facilitate transmembrane transport, was added. The effect of topical application of a lotion containing MSM+EDTA was assessed in two phases of a double blind, placebo controlled clinical trial. In phase 1, patients having swelling in the lower extremities were randomly distributed to receive the MSM+EDTA lotion or a placebo (vehicle) alone. In the second phase, patients were given MSM as placebo followed by MSM+EDTA lotion for 2 weeks. The circumference of calf, ankle and foot for both legs were found to decline significantly after 2 weeks of application of the lotion/ but not placebo, and total antioxidant capacity (FRAP) and lipid peroxidation products (MDA), assayed in blood, showed decline in oxidative stress. Application of MSM alone increased the swelling. Thus EDTA+MSM offers an efficacious treatment for lower extremity pitting edema, through reduction in oxidative stress. PMID:21366964

  18. A double-blind placebo-controlled study into the efficacy of a homeopathic remedy for fear of firework noises in the dog (Canis familiaris).

    PubMed

    Cracknell, Nina R; Mills, Daniel S

    2008-07-01

    Seventy-five dogs that showed a fear response to fireworks participated in a double-blinded, placebo-controlled clinical trial to assess the efficacy of a homeopathic remedy for the alleviation of their behavioural signs. Dogs were randomly assigned to one of two treatments; the homeopathic treatment or the placebo treatment. At the baseline assessments the owners identified the behavioural signs of fear that their dogs normally displayed in response to fireworks, rated their frequency and intensity, and assessed the global severity of their dog's responses. These measures were repeated at the final assessment and owners also completed weekly diaries for the length of the trial. There were significant improvements in the owners' rating of 14/15 behavioural signs of fear in the placebo treatment group and all 15 behavioural signs in the homeopathic treatment group. Both treatment groups also showed significant improvement in the owners' rating of the global severity of their dog's responses. However, there was no significant difference in the response seen between the two treatment groups. PMID:17572119

  19. Incidence of malaria by cotrimoxazole use in HIV-infected Ugandan adults on antiretroviral therapy: a randomised, placebo-controlled study

    PubMed Central

    Kasirye, Ronnie P.; Baisley, Kathy; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Grosskurth, Heiner

    2016-01-01

    Introduction: Previous unblinded trials have shown increased malaria among HIV-infected adults on antiretroviral therapy (ART) who stop cotrimoxazole (CTX) prophylaxis. We investigated the effect of stopping CTX on malaria in HIV-infected adults on ART in a double-blind, placebo-controlled trial. Methods: HIV-infected Ugandan adults stable on ART and CTX with CD4+ cell count at least 250 cells/μl were randomized (1 : 1) to continue CTX or stop CTX and receive matching placebo (COSTOP trial; ISRCTN44723643). Clinical malaria was defined as fever and a positive blood slide, and considered severe if a participant had at least one clinical or laboratory feature of severity or was admitted to hospital. Malaria incidence and rate ratios were estimated using random effects Poisson regression, accounting for multiple episodes. Results: A total of 2180 participants were enrolled and followed for a median of 2.5 years; 453 malaria episodes were recorded. Malaria incidence was 9.1/100 person-years (pyrs) [95% confidence interval (CI) = 8.2–10.1] and was higher on placebo (rate ratio 3.47; CI = 2.74–4.39). Malaria in the placebo arm decreased over time; although incidence remained higher than in the CTX arm, the difference between arms reduced slightly (interaction P value = 0.10). Fifteen participants experienced severe malaria (<1%); overall incidence was 0.30/100 pyrs (CI = 0.18–0.49). There was one malaria-related death (CTX arm). Conclusion: HIV-infected adults – who are stable on ART and stop prophylactic CTX – experience more malaria than those that continue, but this difference is less than has been reported in previous trials. Few participants had severe malaria. Further research might be useful in identifying groups that can safely stop CTX prophylaxis. PMID:26558729

  20. 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

  1. A Phase I Double Blind, Placebo-Controlled, Randomized Study of a Multigenic HIV-1 Adenovirus Subtype 35 Vector Vaccine in Healthy Uninfected Adults

    PubMed Central

    Hayes, Peter; Gill, Dilbinder; Kopycinski, Jakub; Cheeseman, Hannah; Cashin-Cox, Michelle; Naarding, Marloes; Clark, Lorna; Fernandez, Natalia; Bunce, Catherine A.; Hay, Christine M.; Welsh, Sabrina; Komaroff, Wendy; Hachaambwa, Lottie; Tarragona-Fiol, Tony; Sayeed, Eddy; Zachariah, Devika; Ackland, James; Loughran, Kelley; Barin, Burc; Cormier, Emmanuel; Cox, Josephine H.; Fast, Patricia; Excler, Jean-Louis

    2012-01-01

    Background We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35) vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults. Methods Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions) or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively) within one of four dosage groups: Ad35-GRIN/ENV 2×109 (A), 2×1010 (B), 2×1011 (C), or Ad35-GRIN 1×1010 (D) viral particles. Results No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A–D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC) per 106 PBMC to any antigen was 78–139 across Groups A–C and 158–174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A–C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination. Conclusion/Significance Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second vaccination

  2. Atomoxetine Effects on Executive Function as Measured by the BRIEF-A in Young Adults with ADHD: A Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Adler, Lenard A.; Clemow, David B.; Williams, David W.; Durell, Todd M.

    2014-01-01

    Objective To evaluate the effect of atomoxetine treatment on executive functions in young adults with attention-deficit/hyperactivity disorder (ADHD). Methods In this Phase 4, multi-center, double-blind, placebo-controlled trial, young adults (18–30 years) with ADHD were randomized to receive atomoxetine (20–50 mg BID, N = 220) or placebo (N = 225) for 12 weeks. The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) consists of 75 self-report items within 9 nonoverlapping clinical scales measuring various aspects of executive functioning. Mean changes from baseline to 12-week endpoint on the BRIEF-A were analyzed using an ANCOVA model (terms: baseline score, treatment, and investigator). Results At baseline, there were no significant treatment group differences in the percentage of patients with BRIEF-A composite or index T-scores ≥60 (p>.5), with over 92% of patients having composite scores ≥60 (≥60 deemed clinically meaningful for these analyses). At endpoint, statistically significantly greater mean reductions were seen in the atomoxetine versus placebo group for the BRIEF-A Global Executive Composite (GEC), Behavioral Regulation Index (BRI), and Metacognitive Index (MI) scores, as well as the Inhibit, Self-Monitor, Working Memory, Plan/Organize and Task Monitor subscale scores (p<.05), with decreases in scores signifying improvements in executive functioning. Changes in the BRIEF-A Initiate (p = .051), Organization of Materials (p = .051), Shift (p = .090), and Emotional Control (p = .219) subscale scores were not statistically significant. In addition, the validity scales: Inconsistency (p = .644), Infrequency (p = .097), and Negativity (p = .456) were not statistically significant, showing scale validity. Conclusion Statistically significantly greater improvement in executive function was observed in young adults with ADHD in the atomoxetine versus placebo group as measured by changes in the BRIEF

  3. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study

    PubMed Central

    Kapil, Vikas; Khambata, Rayomand S; Robertson, Amy; Caulfield, Mark J; Ahluwalia, Amrita

    2014-01-01

    Single dose administration of dietary inorganic nitrate acutely reduces blood pressure in normotensive healthy volunteers, via bioconversion to the vasodilator nitric oxide. We assessed whether dietary nitrate might provide sustained blood pressure lowering in hypertensive patients.We randomly assigned 68 hypertensive patients in a double-blind, placebo-controlled clinical trial to receive daily dietary supplementation for 4-weeks with either dietary nitrate (250mL daily, as beetroot juice) or a placebo (250mL daily, as nitrate-free beetroot juice) following a 2-week run-in period and followed by a 2-week wash-out. We performed stratified randomization of drug-naïve (n=34) and treated (n=34) hypertensive patients aged 18-85 years. The primary end-point was change in clinic, ambulatory and home blood pressure compared to placebo. Daily supplementation with dietary nitrate was associated with reduction in blood pressure measured by 3 different methods. Mean (95% CI) reduction in clinic blood pressure was 7.7/2.4mmHg (3.6-11-8/0.0-4.9,p<0.001 and p=0.050). 24h ambulatory blood pressure was reduced by 7.7/5.2mmHg (4.1-11.2/2.7-7.7,p<0.001 for both). Home blood pressure was reduced by 8.1/3.8mmHg (3.8-12.4/0.7-6.9,p<0.001 and p<0.01) with no evidence of tachyphylaxis over the 4-week intervention period. Endothelial function improved by ~20% (p<0.001) and arterial stiffness was reduced by 0.59m/s (0.24-0.93;p<0.01) after dietary nitrate consumption with no change after placebo. The intervention was well tolerated. This is the first evidence of durable blood pressure reduction with dietary nitrate supplementation in a relevant patient group. These findings suggest a role for dietary nitrate as an affordable, readily-available, adjunctive treatment in the management of hypertensive patients.(Funded by The British Heart Foundation, Clinicaltrials.gov: NCT01405898). PMID:25421976

  4. Pulsed radiofrequency treatment of the lumbar dorsal root ganglion in patients with chronic lumbar radicular pain: a randomized, placebo-controlled pilot study

    PubMed Central

    Shanthanna, Harsha; Chan, Philip; McChesney, James; Thabane, Lehana; Paul, James

    2014-01-01

    Background No proof of efficacy, in the form of a randomized controlled trial (RCT), exists to support pulsed radiofrequency (PRF) treatment of the dorsal root ganglion (DRG) for chronic lumbar radicular (CLR) pain. We determined the feasibility of a larger trial (primary objective), and also explored the efficacy of PRF in decreasing pain on a visual analog scale (VAS) and improving the Oswestry Disability Index. Methods This was a single-center, placebo-controlled, triple-blinded RCT. Patients were randomized to a placebo group (needle placement) or a treatment group (PRF at 42°C for 120 seconds to the DRG). Patients were followed up for 3 months post procedure. Outcomes with regard to pain, Oswestry Disability Index score, and side effects were analyzed on an intention-to-treat basis. Results Over 15 months, 350 potential patients were identified and 56 were assessed for eligibility. Fifteen of them did not meet the selection criteria. Of the 41 eligible patients, 32 (78%) were recruited. One patient opted out before intervention. Three patients were lost to follow-up at 3 months. Mean VAS differences were not significantly different at 4 weeks (−0.36, 95% confidence interval [CI], −2.29, 1.57) or at 3 months (−0.76, 95% CI, −3.14, 1.61). The difference in mean Oswestry Disability Index score was also not significantly different at 4 weeks (−2%, 95% CI, −14%, 10%) or 3 months (−7%, 95% CI, −21%, 6%). There were no major side effects. Six of 16 patients in the PRF group and three of 15 in the placebo group showed a >50% decrease in VAS score. Conclusion The recruitment rate was partially successful. At 3 months, the relative success of PRF-DRG was small. A large-scale trial to establish efficacy is not practically feasible considering the small effect size, which would necessitate recruitment of a challengingly large number of participants over a number of years. Until clear parameters for application of PRF are established, clinicians will need

  5. Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study.

    PubMed

    Warnholtz, Ascan; Wild, Philipp; Ostad, Mir Abolfazl; Elsner, Veronika; Stieber, Fabian; Schinzel, Reinhard; Walter, Ulrich; Peetz, Dirk; Lackner, Karl; Blankenberg, Stefan; Munzel, Thomas

    2009-05-01

    High-density-lipoproteins-cholesterol (HDL-C) is invertedly related to the incidence of cardiovascular events. Recent studies suggest that HDL-C directly improves endothelial function. Nicotinic acid (niacin) effectively raises serum HDL-C. We therefore hypothesized that treatment with niacin improves endothelial dysfunction in patients with coronary artery disease (CAD). One hundred seven patients with CAD were randomly assigned to double-blinded treatment for 12 weeks with extended-release (ER)-niacin 1000 mg/day (N) or placebo (C), respectively. Flow-mediated dilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent dilation (NMD) and serum lipid concentrations were measured before and after treatment. Triglycerides (P=0.013), low-density-lipoprotein-cholesterol (LDL-C) (P=0.013) and HDL-C (P<0.0001) were altered by N compared to C. Niacin treatment was without effect on FMD or NMD, respectively, compared to placebo. However, post-hoc subgroup analysis revealed an improvement in FMD in patients with low HDL-C at baseline (absolute change in FMD (mean+/-S.D.) N: +3.25+/-3.88%, C: +1.03+/-2.71% in low tertile HDL-C

  6. 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

  7. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: A double-blind placebo-controlled prospective Phase III study by Radiation Therapy Oncology Group 9901

    SciTech Connect

    Ryu, Janice K. . E-mail: janice.ryu@ucdmc.ucdavis.edu; Swann, Suzanne; LeVeque, Francis; Johnson, Darlene J.; Chen, Allan; Fortin, Andre; Kim, Harold; Ang, Kian K.

    2007-03-01

    Purpose: Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients. Methods and Materials: Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 {mu}g/m{sup 2} or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system. Results: Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006). Conclusion: This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.

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

    PubMed Central

    Sugawara, Norio; Ishioka, Masamichi; Tsuchimine, Shoko; Tsuruga, Koji; Sato, Yasushi; Furukori, Hanako; Kudo, Shuhei; Tomita, Tetsu; Nakagami, Taku; Yasui-Furukori, Norio

    2015-01-01

    Background Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs. Aims The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan. Method Using a cross-sectional design, we recruited patients (n = 251) aged 47.7±13.2 (mean±SD) with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials. Results The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation. Conclusions Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias. PMID:26600382

  9. Placebo controls: historical, methodological and general aspects

    PubMed Central

    Walach, Harald

    2011-01-01

    Control conditions were introduced through the trial of Mesmerism in Paris. Placebo controls became codified standard in 1946. Although seemingly unchallenged, there are various problems with this received view. The notion of a placebo is only defined from the negative. A positive notion proposed that placebo effects are effects owing to the meaning an intervention has for an individual. Thus, placebo effects are individualized, whereas standard research paradigms reveal only grossly averaged behaviour. Also, placebo effects are context sensitive, dependent on psychological factors such as expectancy, relief of stress and anxiety, and hence can generate strong and long-lasting treatment effects. These, however, are not predictable. Such a situation can lead to the efficacy paradox: sometimes, sham interventions can be more powerful than proved, evidence-based treatments. This situation has methodological consequences. Placebo-controlled randomized trials reveal only part of the answer, whether an intervention is effective. This is valuable information for regulators, but not necessarily also for patients and of limited value for providers. Hence, I have argued that we need to complement the hierarchical model of evidence by a circular one, in which various methods are employed on equal footing to answer different questions. PMID:21576144

  10. A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

    PubMed Central

    Thorstensson, Rigmor; Trollfors, Birger; Al-Tawil, Nabil; Jahnmatz, Maja; Bergström, Jakob; Ljungman, Margaretha; Törner, Anna; Wehlin, Lena; Van Broekhoven, Annie; Bosman, Fons; Debrie, Anne-Sophie; Mielcarek, Nathalie; Locht, Camille

    2014-01-01

    Background Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration ClinicalTrials.gov NCT01188512 PMID:24421886

  11. Efficacy of intra-articular hyaluronan (Synvisc®) for the treatment of osteoarthritis affecting the first metatarsophalangeal joint of the foot (hallux limitus): study protocol for a randomised placebo controlled trial

    PubMed Central

    Munteanu, Shannon E; Menz, Hylton B; Zammit, Gerard V; Landorf, Karl B; Handley, Christopher J; ElZarka, Ayman; DeLuca, Jason

    2009-01-01

    Background Osteoarthritis of the first metatarsophalangeal joint (MPJ) of the foot, termed hallux limitus, is common and painful. Numerous non-surgical interventions have been proposed for this disorder, however there is limited evidence for their efficacy. Intra-articular injections of hyaluronan have shown beneficial effects in case-series and clinical trials for the treatment of osteoarthritis of the first metatarsophalangeal joint. However, no study has evaluated the efficacy of this form of treatment using a randomised placebo controlled trial. This article describes the design of a randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc®) to reduce pain and improve function in people with hallux limitus. Methods One hundred and fifty community-dwelling men and women aged 18 years and over with hallux limitus (who satisfy inclusion and exclusion criteria) will be recruited. Participants will be randomised, using a computer-generated random number sequence, to receive a single intra-articular injection of up to 1 ml hyaluronan (Synvisc®) or sterile saline (placebo) into the first MPJ. The injections will be performed by an interventional radiologist using fluoroscopy to ensure accurate deposition of the hyaluronan in the joint. Participants will be given the option of a second and final intra-articular injection (of Synvisc® or sterile saline according to the treatment group they are in) either 1 or 3 months post-treatment if there is no improvement in pain and the participant has not experienced severe adverse effects after the first injection. The primary outcome measures will be the pain and function subscales of the Foot Health Status Questionnaire. The secondary outcome measures will be pain at the first MPJ (during walking and at rest), stiffness at the first MPJ, passive non-weightbearing dorsiflexion of the first MPJ, plantar flexion strength of the toe-flexors of the hallux, global satisfaction with the

  12. 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

  13. A split-mouth, randomized, triple-blind, placebo-controlled study to analyze the pre-emptive effect of etoricoxib 120 mg on inflammatory events following removal of unerupted mandibular third molars.

    PubMed

    Costa, F W G; Soares, E C S; Esses, D F S; Silva, P G deB; Bezerra, T P; Scarparo, H C; Ribeiro, T R; Fonteles, C S R

    2015-09-01

    Pain after third molar extraction has been considered the most suitable pharmaceutical model to evaluate acute pain. This study aimed to evaluate the pre-emptive analgesic/anti-inflammatory efficacy of etoricoxib 120 mg following mandibular third molar surgery. A split-mouth, randomized, triple-blind, placebo-controlled study was conducted with patients undergoing the surgical removal of mandibular third molars. All volunteers were allocated randomly to receive either etoricoxib 120 mg or placebo 1h preoperatively, and inflammatory events were evaluated. An estimated sample of 18 surgical units per group was required based on a pilot study (95% confidence level and 80% statistical power). Rescue medication was analyzed by Kaplan-Meier method through log-rank Mantel-Cox test and Pearson linear correlation (P<0.05). Pre-emptive etoricoxib reduced postoperative pain scores significantly in comparison to placebo (P<0.001), with a pain score peak at 6h after surgery (P<0.001). The mean rescue medication consumption was lower in the etoricoxib group compared to the placebo group over the study period (P<0.05). There was no statistically significant difference between groups related to swelling and trismus. The pre-emptive administration of etoricoxib 120 mg significantly reduced the postoperative pain intensity and the need for rescue medication, but did not reduce swelling or trismus. PMID:26144571

  14. A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

    PubMed

    Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

    2007-09-01

    Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base. PMID:18632524

  15. Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

    PubMed

    Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

    2016-09-01

    α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics. PMID:27276401

  16. 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

  17. Photodynamic topical antimicrobial therapy for infected foot ulcers in patients with diabetes: a randomized, double-blind, placebo-controlled study--the D.A.N.T.E (Diabetic ulcer Antimicrobial New Topical treatment Evaluation) study.

    PubMed

    Mannucci, Edoardo; Genovese, Stefano; Monami, Matteo; Navalesi, Giovanni; Dotta, Francesco; Anichini, Roberto; Romagnoli, Fabio; Gensini, Gianfranco

    2014-01-01

    This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm(2) and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (-1.92 ± 1.21, -2.94 ± 1.60, and -3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50 % RPL068 vs. -1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment. PMID:24352342

  18. Effects of luseogliflozin, a sodium-glucose co-transporter 2 inhibitor, on 24-h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, crossover study.

    PubMed

    Nishimura, R; Osonoi, T; Kanada, S; Jinnouchi, H; Sugio, K; Omiya, H; Ubukata, M; Sakai, S; Samukawa, Y

    2015-08-01

    The aim of the present study was to determine the effects of luseogliflozin on 24-h glucose levels, assessed by continuous glucose monitoring, and on pharmacodynamic variables measured throughout the day. In this double-blind, placebo-controlled, crossover study, 37 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized into two groups. Patients in each group first received luseogliflozin then placebo for 7 days each, or vice versa. After 7 days of treatment, the mean 24-h glucose level was significantly lower with luseogliflozin than with placebo [mean (95% confidence interval) 145.9 (134.4-157.5) mg/dl vs 168.5 (156.9-180.0) mg/dl; p < 0.001]. The proportion of time spent with glucose levels ≥70 to ≤180 mg/dl was significantly greater with luseogliflozin than with placebo [median (interquartile range) 83.2 (67.7-96.5)% vs 71.9 (46.9-83.3)%; p < 0.001] without inducing hypoglycaemia. The decrease in glucose levels was accompanied by reductions in serum insulin levels throughout the day. PMID:25930989

  19. Efficacy and Safety of a Lidocaine Gel in Patients from 6 Months up to 8 Years with Acute Painful Sites in the Oral Cavity: A Randomized, Placebo-Controlled, Double-Blind, Comparative Study

    PubMed Central

    Wolf, Dörte; Otto, Joachim

    2015-01-01

    Lidocaine is a well-accepted topical anaesthetic, also used in minors to treat painful conditions on mucosal membranes. This randomized, double-blind, placebo-controlled study (registered prospectively as EudraCT number 2011-005336-25) was designed to generate efficacy and safety data for a lidocaine gel (2%) in younger children with painful conditions in the oral cavity. One hundred sixty-one children were included in two subgroups: 4–8 years, average age 6.4 years, treated with verum or placebo and 6 months–<4 years, average age 1.8 years, treated only with verum. Pain reduction was measured from the time prior to administration to 10 or 30 minutes after. In addition, adverse events and local tolerability were evaluated. In group I, pain was reduced significantly after treatment with verum compared to placebo at both time points. In group II, the individual pain rating shift showed statistically significant lower pain after treatment. Only seven out of 161 patients reported an adverse event but none were classified as being related to the study medication. The local tolerability was assessed as very good in over 97% of cases. For painful sites in the oral cavity, a 2% lidocaine gel is a meaningful tool for short-term treatment in the paediatric population. PMID:26693229

  20. Efficacy and Safety of a Lidocaine Gel in Patients from 6 Months up to 8 Years with Acute Painful Sites in the Oral Cavity: A Randomized, Placebo-Controlled, Double-Blind, Comparative Study.

    PubMed

    Wolf, Dörte; Otto, Joachim

    2015-01-01

    Lidocaine is a well-accepted topical anaesthetic, also used in minors to treat painful conditions on mucosal membranes. This randomized, double-blind, placebo-controlled study (registered prospectively as EudraCT number 2011-005336-25) was designed to generate efficacy and safety data for a lidocaine gel (2%) in younger children with painful conditions in the oral cavity. One hundred sixty-one children were included in two subgroups: 4-8 years, average age 6.4 years, treated with verum or placebo and 6 months-<4 years, average age 1.8 years, treated only with verum. Pain reduction was measured from the time prior to administration to 10 or 30 minutes after. In addition, adverse events and local tolerability were evaluated. In group I, pain was reduced significantly after treatment with verum compared to placebo at both time points. In group II, the individual pain rating shift showed statistically significant lower pain after treatment. Only seven out of 161 patients reported an adverse event but none were classified as being related to the study medication. The local tolerability was assessed as very good in over 97% of cases. For painful sites in the oral cavity, a 2% lidocaine gel is a meaningful tool for short-term treatment in the paediatric population. PMID:26693229

  1. 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

  2. Consumption of cranberry polyphenols enhances human γδ-T cell proliferation and reduces the number of symptoms associated with colds and influenza: a randomized, placebo-controlled intervention study

    PubMed Central

    2013-01-01

    Background Our main objective was to evaluate the ability of cranberry phytochemicals to modify immunity, specifically γδ-T cell proliferation, after daily consumption of a cranberry beverage, and its effect on health outcomes related to cold and influenza symptoms. Methods The study was a randomized, double-blind, placebo-controlled, parallel intervention. Subjects drank a low calorie cranberry beverage (450 ml) made with a juice-derived, powdered cranberry fraction (n = 22) or a placebo beverage (n = 23), daily, for 10 wk. PBMC were cultured for six days with autologous serum and PHA-L stimulation. Cold and influenza symptoms were self-reported. Results The proliferation index of γδ-T cells in culture was almost five times higher after 10 wk of cranberry beverage consumption (p <0.001). In the cranberry beverage group, the incidence of illness was not reduced, however significantly fewer symptoms of illness were reported (p = 0.031). Conclusions Consumption of the cranberry beverage modified the ex vivo proliferation of γδ-T cells. As these cells are located in the epithelium and serve as a first line of defense, improving their function may be related to reducing the number of symptoms associated with a cold and flu. Trial registration ClinicalTrials.gov Identifier: NCT01398150. PMID:24330619

  3. The effects of steroidal contraceptives on the well-being and sexuality of women: a double-blind, placebo-controlled, two-centre study of combined and progestogen-only methods.

    PubMed

    Graham, C A; Ramos, R; Bancroft, J; Maglaya, C; Farley, T M

    1995-12-01

    A placebo-controlled, double-blind study was carried out to assess the direct hormonal effects of combined and progestogen-only oral contraceptives on well-being and sexuality of women in two contrasting cultures. One-hundred-fifty women, who had been sterilised or whose partners had been vasectomised, were recruited from two centres-Manila, Philippines, and Edinburgh, Scotland. After one month pretreatment assessment, women were randomly assigned to one of three treatments (combined oral contraceptive (COC), progestogen-only pill (POP), or placebo; 50 within each treatment group, 25 per centre) and continued on treatment for four months. Assessment was by daily ratings, questionnaires and interviews. The COC adversely affected sexuality in the Edinburgh women, with 12 of the 25 women in this group also reporting the side effect of reduced sexual interest. There were modest negative effects of the combined pill on mood, more noticeable in the Edinburgh women. The POP was associated with no adverse effects on sexuality and some improvement in well-being in both centres. Possible explanations for the apparent lack of adverse effects in the Manila women are discussed. The negative effects reported may be less evident in women using the COC for contraceptive purposes but may lead to discontinuation in some women and warrant further investigation. PMID:8749600

  4. Treatment With Lisdexamfetamine Dimesylate Improves Self- and Informant-Rated Executive Function Behaviors and Clinician- and Informant-Rated ADHD Symptoms in Adults: Data From a Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Weisler, Richard; Ginsberg, Lawrence; Dirks, Bryan; Deas, Patrick; Adeyi, Ben; Adler, Lenard A

    2014-01-24

    Objective: To examine the level of agreement between self- and observer-reported ratings of ADHD symptoms and executive function (EF) behaviors in adults with moderate to severe ADHD and EF deficits. Method: During a 10-week, randomized, double-blind, placebo-controlled study, the effect of lisdexamfetamine dimesylate (LDX) on EF was assessed by self-report and informant report (Behavior Rating Inventory of Executive Function-Adult Version), and ADHD symptoms were assessed by clinician- and informant-rated scales (ADHD Rating Scale IV with adult prompts and Conners' Adult ADHD Rating Scales-Observer Report: Short Version, respectively). Post hoc analysis used Pearson correlations to assess relationships between self- and informant-rated EF and clinician- and informant-rated ADHD symptoms. Results: Correlations between self-ratings versus informant ratings and clinician versus informant ratings were greater at Week 10/early termination (EF: placebo [0.5231-0.6085], LDX [0.3543-0.5167]; ADHD symptoms: placebo [0.4169], LDX [0.4004]) versus baseline (EF: placebo [0.3208-0.5023], LDX [0.2852-0.3439]; ADHD symptoms: placebo [0.1511], LDX [-0.0408]). Conclusion: LDX improved EF and ADHD symptoms, based on participant, informant, and clinician ratings. Increased rater agreement over time may reflect improved symptom awareness. (J. of Att. Dis. XXXX; XX(X) XX-XX). PMID:24464328

  5. 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. PMID:18717569

  6. 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

  7. A Placebo-Controlled, Multicenter, Randomized, Double-Blind, Flexible-Dose, Two-Way Crossover Study to Evaluate the Efficacy and Safety of Sildenafil in Men With Traumatic Spinal Cord Injury and Erectile Dysfunction

    PubMed Central

    Ergin, Sureyya; Gunduz, Berrin; Ugurlu, Hatice; Sivrioglu, Koncuy; Oncel, Sema; Gok, Haydar; Erhan, Belgin; Levendoglu, Funda; Senocak, Ozlem

    2008-01-01

    Background/Objective: To show the efficacy, safety, and tolerability of sildenafil in men with erectile dysfunction (ED) associated with complete or incomplete spinal cord injury (SCI) and to assess its effects on quality of life (QoL) using the Life-Satisfaction Check List. Methods: This was a placebo-controlled, multicenter, randomized, double-blind, flexible-dose, 2-way crossover study with a 2-week washout period between each phase. Patients with ED attributable to SCI (Sexual Health Inventory—Male score ≤21) received 50 to 100 mg sildenafil (n = 24) or placebo (n = 26). Results: Compared with placebo, sildenafil produced higher levels of successful sexual stimulation, intercourse success, satisfaction with sexual life and sexual relationship, erectile function, overall sexual satisfaction, and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score, with no clinically relevant effects on vital signs. Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI, producing significant improvements, compared with placebo, in a number of measures only in patients with incomplete SCI. All patients who expressed a preference selected sildenafil over placebo, although the drug had no effect on patient QoL. Sildenafil was well tolerated, with a profile comparable to that of placebo. Conclusions: Compared with placebo, treatment with oral sildenafil safely and effectively improved erectile function in patients with ED attributable to SCI, especially in those with incomplete injury, and was the agent of choice in those who expressed a preference. PMID:19086709

  8. A First-in-Patient, Multicenter, Double-Blind, 2-Arm, Placebo-Controlled, Randomized Safety and Tolerability Study of a Novel Oral Drug Candidate, CTP-499, in Chronic Kidney Disease.

    PubMed

    Sabounjian, LuAnn; Graham, Philip; Wu, Lijun; Braman, Virginia; Cheng, Changfu; Liu, Julie; Shipley, James; Neutel, Joel; Dao, Michael

    2016-07-01

    The prevalence of chronic kidney disease (CKD) related to type 2 diabetes is increasing worldwide. In addition to standard of care, treatment with anti-inflammatory and antifibrotic agents such as CTP-499, a novel oral, multisubtype selective inhibitor of phosphodiesterases, may be important in CKD treatment. A phase 1b randomized, double-blind, placebo-controlled clinical trial of CTP-499 in CKD patients (25 active, 8 placebo) with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m(2) was conducted to assess safety and tolerability. Secondary outcomes included pharmacokinetics and exploratory effects on inflammatory and hematology markers. Patients received 600 mg CTP-499 or matching placebo tablets orally once daily for 2 weeks, then twice daily for 2 additional weeks. CTP-499 was well tolerated with no serious or severe adverse events, or adverse events leading to discontinuation. CTP-499 was rapidly absorbed and produced acceptable interpatient variability. Of the 5 metabolites (M1-M5), M5 was the most abundant in plasma and urine. Exposure to CTP-499 and metabolites was higher in CKD patients than previously reported in healthy volunteers. No statistically significant differences were detected between the CTP-499- and placebo-treated groups for any of the biomarkers tested. This study provides data supporting further evaluation of CTP-499 in CKD patients. PMID:27310332

  9. A Single-Center, Randomized Double-Blind Placebo-Controlled Study Evaluating the Effects of Poly-Gamma-Glutamate on Human NK Cell Activity after an 8-Week Oral Administration in Healthy Volunteers

    PubMed Central

    Kim, Kyung-Soo; Lee, Tae-Young; Hong, Jang-Hee; Kim, Ahrom; Kim, Sung-Jin; Choi, Jai-Chul; Sung, Moon-Hee; Poo, Haryoung

    2013-01-01

    A randomized double-blind placebo-controlled immunity study involving 99 healthy volunteers was performed to investigate the effect of poly-γ-glutamate (γ-PGA) on human natural killer (NK) cell activity in peripheral blood. The volunteers were randomly assigned to one of three groups and orally treated with solutions (25 mL) containing 0 mg (placebo), 250 mg (low dosage), or 500 mg (high dosage) of γ-PGA. Each volunteer took one dose every 12 hours for 8 weeks. Blood samples were drawn before the initial treatment and at the 4th and the 8th weeks of treatment. NK cell activity was assessed by measuring its degranulation, cytokine production, and cytotoxicity against the K562 cell line. Our results revealed that the cytotoxic activities of NK cells from the high-dosage γ-PGA group were significantly higher (P < 0.05 for all comparisons) compared to the low dosage and placebo groups at weeks 4 and 8 after the initial treatment. This increase in the NK cell activity among peripheral blood mononuclear cells (PBMCs) of healthy individuals was also confirmed in vitro (as assessed by the degranulation and cytokine production). These results suggest that the oral administration of γ-PGA induces a cell-mediated immunity by increasing the NK cell activity in humans. PMID:24454502

  10. A single-center, randomized double-blind placebo-controlled study evaluating the effects of poly-gamma-glutamate on human NK cell activity after an 8-week oral administration in healthy volunteers.

    PubMed

    Kim, Kyung-Soo; Lee, Tae-Young; Hong, Jang-Hee; Kim, Ahrom; Kim, Sung-Jin; Choi, Jai-Chul; Sung, Moon-Hee; Poo, Haryoung

    2013-01-01

    A randomized double-blind placebo-controlled immunity study involving 99 healthy volunteers was performed to investigate the effect of poly- γ -glutamate ( γ -PGA) on human natural killer (NK) cell activity in peripheral blood. The volunteers were randomly assigned to one of three groups and orally treated with solutions (25 mL) containing 0 mg (placebo), 250 mg (low dosage), or 500 mg (high dosage) of γ -PGA. Each volunteer took one dose every 12 hours for 8 weeks. Blood samples were drawn before the initial treatment and at the 4th and the 8th weeks of treatment. NK cell activity was assessed by measuring its degranulation, cytokine production, and cytotoxicity against the K562 cell line. Our results revealed that the cytotoxic activities of NK cells from the high-dosage γ -PGA group were significantly higher (P < 0.05 for all comparisons) compared to the low dosage and placebo groups at weeks 4 and 8 after the initial treatment. This increase in the NK cell activity among peripheral blood mononuclear cells (PBMCs) of healthy individuals was also confirmed in vitro (as assessed by the degranulation and cytokine production). These results suggest that the oral administration of γ -PGA induces a cell-mediated immunity by increasing the NK cell activity in humans. PMID:24454502

  11. A Double-Blind, Placebo-Controlled Study Investigating the Effects of Omega-3 Supplementation in Children Aged 8-10 Years from a Mainstream School Population

    ERIC Educational Resources Information Center

    Kirby, A.; Woodward, A.; Jackson, S.; Wang, Y.; Crawford, M. A.

    2010-01-01

    Despite the increased interest in the effects of omega-3 supplementation on childrens' learning and behaviour, there are a lack of controlled studies of this kind that have utilised a typically developing population. This study investigated the effects of omega-3 supplementation in 450 children aged 8-10 years old from a mainstream school…

  12. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis: results of a placebo-controlled, monosequence crossover, non-randomised, single-blind pilot study

    PubMed Central

    Terkeltaub, R; Sundy, J S; Schumacher, H R; Murphy, F; Bookbinder, S; Biedermann, S; Wu, R; Mellis, S; Radin, A

    2009-01-01

    Background: Recent studies suggest that blockade of the NLRP3 (cryopyrin) inflammasome interleukin 1β (IL1β) pathway may offer a new treatment strategy for gout. Objective: To explore the potential utility of rilonacept (IL1 Trap) in patients with chronic active gouty arthritis in a proof-of-concept study. Methods: This 14-week, multicentre, non-randomised, single-blind, monosequence crossover study of 10 patients with chronic active gouty arthritis included a placebo run-in (2 weeks), active rilonacept treatment (6 weeks) and a 6-week post-treatment follow-up. Results: Rilonacept was generally well tolerated. No deaths and no serious adverse events occurred during the study. One patient withdrew owing to an injection-site reaction. Patients’ self-reported median pain visual analogue scale scores significantly decreased from week 2 (after the placebo run-in) to week 4 (2 weeks of rilonacept) (5.0 to 2.8; p<0.049), with sustained improvement at week 8 (1.3; p<0.049); 5 of 10 patients reported at least a 75% improvement. Median symptom-adjusted and severity-adjusted joint scores were significantly decreased. High-sensitivity C-reactive protein levels fell significantly. Conclusions: This proof-of-concept study demonstrated that rilonacept is generally well tolerated and may offer therapeutic benefit in reducing pain in patients with chronic refractory gouty arthritis, supporting the need for larger, randomised, controlled studies of IL1 antagonism such as with rilonacept for this clinical indication. PMID:19635719

  13. Phase II, Randomized, Placebo-controlled, 90-day Study of Emixustat HCL in Geographic Atrophy Associated with Dry Age-Related Macular Degeneration

    PubMed Central

    Dugel, Pravin U.; Novack, Roger L.; Csaky, Karl G.; Richmond, Preston P.; Birch, David G.; Kubota, Ryo

    2015-01-01

    Purpose This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Methods Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity following a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events (AEs) and ophthalmic examinations. Results Seventy-two subjects (54 emixustat, 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14, and was reversible within 7-14 days after drug cessation. No systemic AEs of concern were noted. Dose-related ocular AEs (chromatopsia, 57% emixustat vs. 17% placebo; and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate, and the majority resolved on study or within 7-14 days after study drug cessation. Conclusions In this phase II study, emixustat produced a dose-dependent, reversible effect on rod function, and an ocular AE profile that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of GA associated with dry AMD. PMID:25932553

  14. 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

  15. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Naltrexone to Counteract Antipsychotic-Associated Weight Gain: Proof of Concept

    PubMed Central

    Tek, Cenk; Ratliff, Joseph; Reutenauer, Erin; Ganguli, Rohan; O’Malley, Stephanie S.

    2014-01-01

    Patients with schizophrenia suffer from higher rates of obesity and related morbidity and mortality than the general population. Women with schizophrenia are at particular risk for antipsychotic-induced weight gain, obesity, and related medical disorders such as diabetes and cardiovascular disease. Given preclinical studies revealing the role of the endogenous opioid systems in human appetite and the potential of antipsychotic medications to interfere with this system, we hypothesized that opioid antagonists may be beneficial in arresting antipsychotic-induced weight gain and promoting further weight loss in women with schizophrenia. In the present study, 24 overweight women with a diagnosis of schizophrenia or schizoaffective disorder were randomized to placebo (PLA) or naltrexone (NTX) 25mg/day for 8 weeks. The primary outcome measure was change in body weight from baseline. Patients in the NTX group had significant weight loss (−3.40kg) compared to weight gain (+1.37kg) in the PLA group. Mainly non-diabetic subjects lost weight in the naltrexone arm. These data support the need to further investigate the role of D2 blockade in reducing food reward based overeating. A larger study addressing the weaknesses of this pilot study is currently underway. PMID:25102328

  16. 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…

  17. Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a phase II/III multicentre, randomised, double-blind, placebo-controlled trial

    PubMed Central

    Katayama, Kanako; Misawa, Sonoko; Sato, Yasunori; Sobue, Gen; Yabe, Ichiro; Watanabe, Osamu; Nishizawa, Masatoyo; Kusunoki, Susumu; Kikuchi, Seiji; Nakashima, Ichiro; Ikeda, Shu-ichi; Kohara, Nobuo; Kanda, Takashi; Kira, Jun-ichi; Hanaoka, Hideki; Kuwabara, Satoshi

    2015-01-01

    Introduction Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell dyscrasia and the overproduction of the vascular endothelial growth factor (VEGF). Recently, the prognosis of POEMS was substantially improved by introduction of therapeutic intervention for myeloma. However, no randomised clinical trial has been performed because of the rarity and severity of the disease. Methods and analysis The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome, with an additional 48-week open-label safety study. Adults with POEMS syndrome who have no indication for transplantation are assessed for eligibility at 12 tertiary neurology centres in Japan. Patients who satisfy the eligibility criteria are randomised (1:1) to receive thalidomide (100–300 mg daily) plus dexamethasone (12 mg/m2 on days 1–4 of a 28-day cycle) or placebo plus dexamethasone. Both treatments were administered for 24 weeks (six cycles; randomised comparative study period). Patients who complete the randomised study period or show subacute deterioration during the randomised period participate in the subsequent 48-week open-label safety study (long-term safety period). The primary end point of the study is the reduction rate of serum VEGF levels at 24 weeks. Ethics and dissemination The protocol was approved by the Institutional Review Board of each hospital. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, Japan (No. 22-1716). The J-POST Trial is currently ongoing and is due to finish in August 2015. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations and will also be disseminated to participants. Trial registration number

  18. Efficacy and safety of a flaxseed hull extract in the symptomatic management of benign prostatic hyperplasia: a parallel, randomized, double-blind, placebo-controlled, pilot study.

    PubMed

    Simons, Rudy; Sonawane, Navneet; Verbruggen, Marian; Chaudhary, Jayesh

    2015-02-01

    This exploratory study was designed to assess the effectiveness of a lignan-rich extract of flaxseed hulls (LinumLife EXTRA(®)) in alleviating symptoms in subjects with benign prostatic hyperplasia (BPH) compared with placebo. Two dosages of extract were compared against placebo in a double-blinded, randomized, parallel, multicenter study. Newly diagnosed cases of BPH in patients aged 45-75 years with an American Urological Association Symptom Index (AUASI) score of ≥13 were included. Study treatment consisted of 500 or 1000 mg of extract containing 100 mg (low-dose active [LDA] group, n=26) or 200 mg (high-dose active [HDA] group, n=26) of secoisolariciresinol diglucoside (SDG), respectively. The placebo (P) group (n=28) received matching maltodextrin capsules. Sixty subjects (LDA [n=19], HDA [n=20], and P [n=21]) completed the study as per the protocol requirements. Change in the AUASI score within a period of 8 weeks, from baseline to end of treatment, was assessed. Significant improvement of obstructive symptoms and management of irritable BPH symptoms was achieved in all groups after treatment. Due to a strong placebo effect, there was no statistical difference between the groups that were treated with flaxseed hull extract as compared with the placebo group. Treatment with flaxseed hull extract did not lead to adverse effects compared with placebo. Supplementation with flaxseed hull extract was found to be safe and well-tolerated and may have improved the quality of life of individuals with BPH. The significant placebo effect as well as the number of subjects per treatment group and the relative short duration of the study may explain the lack of statistical significance between groups. PMID:25546379

  19. Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of green tea in preventing acute gastrointestinal complications due to radiotherapy

    PubMed Central

    Emami, Hamid; Nikoobin, Farzaneh; Roayaei, Mahnaz; Ziya, Hamid Reza

    2014-01-01

    Background: Radiation-induced discomfort is frequently observed during pelvic radiotherapy. This study was performed to determine the effect of a green tea tablet to reduce the incidence of radiation-induced diarrhea and vomiting in patients with abdomen and pelvic malignancy. Materials and Methods: This randomized controlled clinical trial recruited 42 patients with abdomen and pelvic malignancy considered for treatment with 50 Gy radiotherapy, randomly assigned to the green tea tablet 450 mg (n = 21) or placebo group (n = 21) for 5 weeks. Acute gastrointesinal complications (Diarrhea and vomiting) were weekly assessed using Common Toxicity Criteria of the National Cancer Institute version 3.0 and functional living index emesis, respectively. Two-sample t-tests, Pearson's Chi-square, Mann-Whitney U-test, and Friedman were used for analysis. Results: There was a significant difference in frequency of reported diarrhea between two groups of study at the end of study (P < 0.002). About 81% of patients in green tea group reported no history of diarrhea at week 5. The treatment group have reported no history of severe diarrhea during radiotherapy. There was no significant difference between two groups of study in frequency of vomiting throughout the study, but 9.5% of cases in placebo group showed severe vomiting. Conclusion: Green tea contains a high concentration of catechins could be effective in decreasing the frequency and severity of radiotherapy induced diarrhea. Green tea (450 mg/day) could be considered to be a safe for prevention diarrhea and vomiting in patients undergoing pelvic or abdomen radiotherapy. PMID:25097628

  20. Double-Blind, Placebo-Controlled Pilot Study of Processed Ultra Emu Oil Versus Placebo in the Prevention of Radiation Dermatitis

    SciTech Connect

    Rollmann, Denise C.; Novotny, Paul J.; Petersen, Ivy A.; Garces, Yolanda I.; Bauer, Heather J.; Yan, Elizabeth S.; Wahner-Roedler, Dietlind; Vincent, Ann; Sloan, Jeff A.; Issa Laack, Nadia N.

    2015-07-01

    Purpose: The purpose of this single-institution pilot study was to evaluate the feasibility and safety of an oil-based skin agent, Ultra Emu Oil, on skin-related toxicity in patients undergoing radiation therapy to the breast or chest wall. Methods and Materials: Patients were randomized 2:1 in a double-blind fashion and were instructed to apply processed Ultra Emu Oil or placebo (cottonseed oil) twice daily during the course of radiation therapy. The oils were applied before the third fraction and continued for 6 weeks after completion of treatment. The primary endpoint was the area under the curve (AUC) of Skindex-16 scale scores over time. Secondary outcomes included maximum grade of radiation dermatitis using the Common Terminology Criteria (CTC) for Adverse Events (CTCAE 3.0), the Skin Toxicity Assessment Tool, quality of life (QOL) measured by Linear Analogue Self-Assessment, and a symptom experience diary (SED). Results: In all, 42 of 45 patients completed the study and were evaluable. The median times to peak rash, skin redness, peeling, and skin swelling were weeks 6, 6, 7, and 7, respectively as measured by the SED. The Skindex AUC scores tended to be lower in emu oil patients than in placebo patients (mean total AUC 7.2 vs 10.4, respectively). This trend was also seen in all the Skindex subdomains. The overall QOL was slightly better in the emu oil group but remained stable throughout the study for both arms. Peak CTC toxicity occurred at week 6. Patients using emu oil appeared slightly worse on maximum CTC grade, but the difference was not significant. Conclusions: This pilot study confirmed the safety of oil-based skin treatments during radiation therapy and suggests a trend for reduced skin toxicity for patients receiving emu oil. A larger study is needed to evaluate the efficacy of emu oil in reducing radiation dermatitis in patients receiving breast radiation.

  1. The effect of 6-week treatment with escitalopram on CCK-4 challenge: a placebo-controlled study in CCK-4-sensitive healthy volunteers.

    PubMed

    Tõru, Innar; Maron, Eduard; Raag, Mait; Vasar, Veiko; Nutt, David J; Shlik, Jakov

    2013-07-01

    Cholecystokinin-tetrapeptide (CCK-4)-induced panic attacks are reportedly attenuated by effective treatment with antipanic antidepressants in patients with panic disorder, but in healthy volunteers such effects are not well studied. The aim of this study was to assess the effect of 6-week treatment with an SSRI escitalopram on CCK-4-induced symptoms in healthy volunteers, who previously responded with a panic attack to CCK-4 challenge. A total of 18 healthy subjects (10 males and eight females, mean age 22.5 ± 5.8) received a 6-week treatment with escitalopram (10 mg/day) and placebo followed by CCK-4 challenge (50 μg) in a double-blind crossover design. The panic rate was 67% after treatment with escitalopram and 56% after treatment with placebo (p = 0.7). Thus, the results showed a significant reduction in CCK-4-induced panic rates without significant differences between escitalopram and placebo conditions. There were no significant effects of either treatment on any other variable of anxiety or cardiovascular indices. Secondary analysis showed no effect of gender or 5-HTTLPR polymorphism on response to CCK-4 challenge. This study demonstrated that in contrast to the findings in patients with panic disorder, in CCK-4-sensitive healthy volunteers the treatment with an antipanic SSRI did not cause a reduction of CCK-4-induced panic attacks beyond the effect of placebo. The mechanisms behind this discrepancy and the reasons of the decrease in sensitivity to CCK-4 challenge on repeated administration remain to be clarified in future studies. PMID:22939006

  2. Multicentre, randomised, placebo-controlled trial of extract of Japanese herbal medicine Daikenchuto to prevent bowel dysfunction after adult liver transplantation (DKB 14 Study)

    PubMed Central

    Kaido, Toshimi; Shimamura, Tsuyoshi; Sugawara, Yasuhiko; Sadamori, Hiroshi; Shirabe, Ken; Yamamoto, Michio; Uemoto, Shinji

    2015-01-01

    Introduction This multicentre randomised controlled clinical trial will aim to determine the ability of an extract (TJ-100) of Daikenchuto (traditional Japanese herbal medicine; Kampo) to prevent bowel dysfunction in at least 110 patients after liver transplantation (LT). Methods and analysis The following co-primary end points will be evaluated on postoperative day 7: total oral and enteral caloric intake, abdominal distension and abdominal pain. The secondary end points will comprise sequential changes of total oral and enteral caloric intake after LT, sequential changes in numeric rating scales for abdominal distension and pain, elapsed time to the first postoperative passage of stool, quality of life assessment using the Gastrointestinal Symptom Rating Scale score (Japanese version), postoperative liver function, liver regeneration rate, incidence of bacteraemia and bacterial strain, trough level of immunosuppressants, occurrence of acute cellular rejection, discharge or not within 2 months after LT, sequential changes of portal venous flow to the graft and ascites discharge. The two arms of the study will comprise 55 patients per arm. Ethics and dissemination The study has been conducted according to the CONSORT statement. All participants signed a written consent form, and the study has been approved by the institutional review board of each participating institute and conducted in accordance with the Declaration of Helsinki of 1996. The findings will be disseminated through scientific and professional conferences, and in peer-reviewed journals. Trial registration number The DKB 14 Study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN-CTR), Japan (registration number: UMIN000014326) during 2014. PMID:26419681

  3. Lubiprostone decreases the small bowel transit time by capsule endoscopy: an exploratory, randomised, double-blind, placebo-controlled 3-way crossover study.

    PubMed

    Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

    2014-01-01

    The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE. PMID:25614738

  4. Lubiprostone Decreases the Small Bowel Transit Time by Capsule Endoscopy: An Exploratory, Randomised, Double-Blind, Placebo-Controlled 3-Way Crossover Study

    PubMed Central

    Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

    2014-01-01

    The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117–407) minutes in the P-P regimen, 122.5 (27–282) minutes in the L-P regimen, and 110.5 (11–331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE. PMID:25614738

  5. Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: a double blind, placebo-controlled study.

    PubMed

    Young, Joel L

    2013-05-15

    The purpose of this study was to assess the efficacy of lisdexamfetamine dimesylate (LDX) for the treatment of executive functioning deficits in adults (ages 18-60) with chronic fatigue syndrome (CFS). The study's primary outcome measure was the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A). Secondary outcome measures were standardized assessments of fatigue, pain and global functioning. Twenty-six adults who met criteria for CFS and had clinically significant executive functioning deficits were randomly assigned to a flexible morning dose (30, 50, 70 mg/day) of either placebo or LDX for a 6-week trial. The data were analyzed with standard analysis of variance (ANOVA) procedures. Participants in the LDX group showed significantly more positive change in BRIEF-A scores (Mchange=21.38, SD=15.85) than those in the placebo group (Mchange=3.36, SD=7.26). Participants in the active group also reported significantly less fatigue and generalized pain relative to the placebo group. Although future studies with LDX should examine whether these benefits generalize to larger, more diverse samples of patients, these results suggest that LDX could be a safe and efficacious treatment for the executive functioning deficits often associated with CFS. The possibility that dopaminergic medications could play an important role addressing the symptoms of CFS is also discussed. PMID:23062791

  6. A Randomised, Double-Blind, Placebo-Controlled Trial of Actovegin in Patients with Post-Stroke Cognitive Impairment: ARTEMIDA Study Design

    PubMed Central

    Guekht, Alla; Skoog, Ingmar; Korczyn, Amos D.; Zakharov, Vladimir; Eeg, Martin; Vigonius, Ulf

    2013-01-01

    Background No drug treatment to date has shown convincing clinical evidence of restoring cognitive function or preventing further decline after stroke. The ongoing ARTEMIDA study will evaluate the efficacy and safety of Actovegin for the symptomatic treatment of post-stroke cognitive impairment (PSCI) and will explore whether Actovegin has any disease-modifying effect by assessing whether any changes are sustained after treatment. Design ARTEMIDA is a 12-month, multicentre trial in patients (planned a total of 500, now recruited) with cognitive impairment following ischaemic stroke. The study consists of a baseline screening (≤7 days after stroke), after which eligible patients are randomised to Actovegin (2,000 mg/day for up to 20 intravenous infusions followed by 1,200 mg/day orally) or placebo for a 6-month double-blind treatment period. Patients will be followed up for a further 6 months, during which time they will be treated in accordance with standard clinical practice. The primary study endpoint is change from baseline in the Alzheimer's Disease Assessment Scale, cognitive subscale, extended version. Secondary outcomes include: Montreal Cognitive Assessment; dementia diagnosis (ICD-10); National Institutes of Health Stroke Scale; Barthel Index; EQ-5D; Beck Depression Inventory, version II, and safety. Conclusion There is a clear need for effective treatments for PSCI. ARTEMIDA should provide important insights into the use of a novel drug therapy for PSCI. PMID:24516413

  7. 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

  8. Granulocyte Colony-Stimulating Factor for Amyotrophic Lateral Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Study of Iranian Patients

    PubMed Central

    Amirzagar, Nasibeh; Nafissi, Shahriar; Tafakhori, Abbas; Modabbernia, Amirhossein; Amirzargar, Aliakbar; Ghaffarpour, Majid; Siroos, Bahaddin

    2015-01-01

    Background and Purpose The aim of this study was to determine the efficacy and tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with amyotrophic lateral sclerosis (ALS). Methods Forty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 µg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline. Results The rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's ρ=0.370, p=0.070). Conclusions With the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females. PMID:25851895

  9. Effects of a topically applied counterirritant (Eucalyptamint) on cutaneous blood flow and on skin and muscle temperatures. A placebo-controlled study.

    PubMed

    Hong, C Z; Shellock, F G

    1991-02-01

    This study was designed to investigate the effects of a new product of counterirritant, Eucalyptamint, on the cutaneous circulation and on skin and muscle temperatures. Ten normal subjects (six males and four females, with an average age of 34 +/- 6 yr) were involved in this study. Eucalyptamint was applied to the anterior forearm skin of one side, and placebo was applied to the contralateral forearm. The subjective feelings, cutaneous blood flow, and skin temperature were measured before and periodically (5-min intervals) after the application of the compound. Muscle temperature was measured before and 30 min after the application of the Eucalyptamint. There was no significant effect on the subjective sensation. However, there were statistically significant (P less than 0.05) increases in cutaneous blood flow (up to 4 times base-line) and skin temperatures (up to 0.8 degrees C higher than base-line) after the application of Eucalyptamint with the effects lasting up to 45 min after the application. The muscle temperature was also increased (0.4 degrees C) significantly (P less than 0.05) 30 min after application of the Eucalyptamint. There were no significant changes in the placebo application. The results of this study suggested that the new product of counterirritant, Eucalyptamint, produced significant physiologic responses that may be beneficial for pain relief and/or useful to athletes as a passive form of warm-up. PMID:1994967

  10. A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure

    PubMed Central

    Ponikowski, Piotr; Mitrovic, Veselin; Ruda, Mikhail; Fernandez, Alberto; Voors, Adriaan A.; Vishnevsky, Alexander; Cotter, Gad; Milo, Olga; Laessing, Ute; Zhang, Yiming; Dahlke, Marion; Zymlinski, Robert; Metra, Marco

    2014-01-01

    Aims The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF). Methods and results This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, systolic blood pressure (BP) ≥115 mmHg, and estimated glomerular filtration rate ≥30 mL/min/1.73 m2 to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n = 32; placebo, n = 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: −2.44 mmHg, P = 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: −5.17 mmHg at 4 h, P < 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns. Conclusion The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients. ClinicalTrials.gov identifier NCT01543854. PMID:24255129

  11. A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia.

    PubMed

    Pandina, Gahan J; Lindenmayer, Jean-Pierre; Lull, Julia; Lim, Pilar; Gopal, Srihari; Herben, Virginie; Kusumakar, Vivek; Yuen, Eric; Palumbo, Joseph

    2010-06-01

    This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or gluteal [corrected] on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P < or = 0.034) in all the paliperidone palmitate dose-groups versus placebo. Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle. Common treatment-emergent adverse events (> or =2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with > or =1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia. PMID:20473057

  12. Effect of 3 weeks of continuous positive airway pressure treatment on mood in patients with obstructive sleep apnoea: a randomized placebo-controlled study

    PubMed Central

    Lee, In-Soo; Bardwell, Wayne; Ancoli-Israel, Sonia; Loredo, Jose S.; Dimsdale, Joel E.

    2011-01-01

    Background Patients with obstructive sleep apnoea (OSA) commonly have mood symptoms such as depression and anxiety. However, the results of randomized controlled trials on the therapeutic effect of CPAP on mood symptoms have been inconsistent. The present study examined whether 3 weeks of CPAP treatment had specific therapeutic effects on mood symptoms in patients with OSA compared with placebo. Methods A double-blind, parallel, randomized controlled trial using therapeutic and placebo CPAP was performed in 71 patients newly diagnosed with OSA [apnoea-hypopnoea index (AHI) ≥10]. Mood was assessed by the Center for Epidemiologic Studies-Depression (CES-D) Scale, the Profile of Mood States (POMS) and the Brief Symptom Inventory (BSI) before and after 3 weeks of treatment. AHI was used to assess the severity of apnoea. The two groups were compared using a simple comparison of the changes within each arm and repeated measures analysis of variance. Results Fifty-six subjects completed the study: 26 in the CPAP group and 30 in the placebo group. The two groups were well matched at baseline, with no significant differences in demographic, mood and apnoea variables. Both groups had severe apnoea, and mild depression and anxiety at baseline. After 3 weeks of treatment, AHI decreased significantly in the CPAP group. The mean change in AHI was −30.7 [standard deviation (SD) 23.1] in the CPAP group and −5.8 (SD 18.3) in the placebo group (difference between groups P<0.001). However, after 3 weeks of treatment, there were no significant time by treatment effects in relation to mood, as assessed by the CES-D, POMS Depression, POMS Tension, BSI Depression or BSI Anxiety (all P>0.05). Conclusion In conclusion, 3 weeks of CPAP treatment did not show a specific therapeutic effect on mood symptoms in patients with OSA. PMID:22172966

  13. Safety and immunogenicity of pentavalent rotavirus vaccine in a randomized, double-blind, placebo-controlled study in healthy elderly subjects

    PubMed Central

    Lawrence, Jody; He, Su; Martin, Jason; Schödel, Florian; Ciarlet, Max; Murray, Alexander V

    2014-01-01

    Rotavirus may be an important causative agent of acute gastroenteritis (AGE) in the elderly, a population that is particularly vulnerable due to waning immunity. It is estimated that rotavirus may account for 2–5% of adult gastroenteritis hospitalizations in the United States. This is the first study to assess the safety and immunogenicity of the live pentavalent rotavirus vaccine (RV5) in an elderly population. In this study, healthy, independently living adults aged 65–80 years were randomized in a 2:1 ratio to receive three 2-mL oral doses of RV5 or placebo administered 28–42 days apart. All subjects were followed for safety for 42 days post any vaccination and up to 180 days after the final vaccination for clinical adverse events. Immunogenicity of RV5 was measured by serum anti-rotavirus IgA enzyme immunoassay and serum neutralizing antibody responses to human rotavirus serotypes prior to and after each dose. Results of this study demonstrated that RV5 was generally safe and well tolerated in healthy elderly adults, where 9% of placebo and 27% of RV5 recipients experienced a vaccine-related adverse event of mild or moderate intensity. Immune responses (serum anti-rotavirus immunoglobulin A [IgA] and serum neutralizing antibodies against human rotavirus serotypes in the vaccine) were augmented in this population after a single dose of RV5, despite the factors of older age and preexisting antibodies to the virus. Therefore, if vaccination in the elderly is needed, further evaluation of RV5 as a candidate vaccine in this age group may be warranted. PMID:25424929

  14. 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

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

    PubMed Central

    Vinson, Joe A; Burnham, Bryan R; Nagendran, Mysore V

    2012-01-01

    Background Adult weight gain and obesity have become worldwide problems. Issues of cost and potential side effects of prescription weight loss drugs have led overweight and obese adults to try nutraceuticals that may aid weight loss. One promising nutraceutical is green coffee extract, which contains high concentrations of chlorogenic acids that are known to have health benefits and to influence glucose and fat metabolism. A 22-week crossover study was conducted to examine the efficacy and safety of a commercial green coffee extract product GCA™ at reducing weight and body mass in 16 overweight adults. Methods Subjects received high-dose GCA (1050 mg), low-dose GCA (700 mg), or placebo in separate six-week treatment periods followed by two-week washout periods to reduce any influence of preceding treatment. Treatments were counterbalanced between subjects. Primary measurements were body weight, body mass index, and percent body fat. Heart rate and blood pressure were also measured. Results Significant reductions were observed in body weight (−8.04 ± 2.31 kg), body mass index (−2.92 ± 0.85 kg/m2), and percent body fat (−4.44% ± 2.00%), as well as a small decrease in heart rate (−2.56 ± 2.85 beats per minute), but with no significant changes to diet over the course of the study. Importantly, the decreases occurred when subjects were taking GCA. Body mass index for six subjects shifted from preobesity to the normal weight range (<25.00 kg/m2). Conclusion The results are consistent with human and animal studies and a meta-analysis of the efficacy of green coffee extract in weight loss. The results suggest that GCA may be an effective nutraceutical in reducing weight in preobese adults, and may be an inexpensive means of preventing obesity in overweight adults. PMID:22291473

  16. Short-term efficacy of calcium fructoborate on subjects with knee discomfort: a comparative, double-blind, placebo-controlled clinical study

    PubMed Central

    Pietrzkowski, Zbigniew; Phelan, Michael J; Keller, Robert; Shu, Cynthia; Argumedo, Ruby; Reyes-Izquierdo, Tania

    2014-01-01

    Calcium fructoborate (CFB) at a dose of 110 mg twice per day was previously reported to improve knee discomfort during the first 14 days of treatment. In this study, 60 participants with self-reported knee discomfort were randomized into two groups receiving CFB or placebo. Initial levels of knee discomfort were evaluated by Western Ontario and McMaster Universities Arthritis Index (WOMAC) and McGill Pain Questionnaire (MPQ) scores at the beginning of the study and also at 7 and 14 days after treatment. Results showed that supplementation with CFB significantly improved knee discomfort in the study subjects; significant reductions of mean within-subject change in WOMAC and MPQ scores were observed for the CFB group compared to the placebo group at both 7 and 14 days after treatment. Estimated treatment differences for the MPQ score were −5.8 (P=0.0009) and −8.9 (P<0.0001) at Day 7 and 14, respectively. Estimated differences for the WOMAC score were −5.3 (P=0.06) and −13.73 (P<0.0001) at Day 7 and 14, respectively. Negative values indicate greater reductions in reported discomfort. On both Day 7 and Day 14, the trend was toward greater improvement in the CFB group. The placebo group did not exhibit any change in the WOMAC and MPQ scores. In conclusion, supplementation with 110 mg CFB twice per day was associated with improving knee discomfort during the 2 weeks of intake. PMID:24940052

  17. Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

    PubMed Central

    Strasser, F; Lutz, T A; Maeder, M T; Thuerlimann, B; Bueche, D; Tschöp, M; Kaufmann, K; Holst, B; Brändle, M; von Moos, R; Demmer, R; Cerny, T

    2008-01-01

    Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 μg kg−1 (lower-dose) ghrelin; 11 received 8 μg kg−1 (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4–5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml−1 with lower-dose and 42 ng ml−1 with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (P<0.05) for upper-dose patients at end of study (3580 pg ml−1) than at baseline (990 pg ml−1). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower- and upper-dose group. PMID:18182992

  18. Efficacy of drug treatment for acute mania differs across geographic regions: An individual patient data meta-analysis of placebo-controlled studies.

    PubMed

    Welten, Carlijn C M; Koeter, M W J; Wohlfarth, T D; Storosum, J G; van den Brink, W; Gispen-de Wied, C C; Leufkens, H G M; Denys, D A J P

    2015-08-01

    Given globalization trends in the conduct of clinical trials, the external validity of trial results across geographic regions is questioned. The objective of this study was to examine the efficacy of treatment in acute mania in bipolar disorder across regions and to explain potential differences by differences in patient characteristics. We performed a meta-analysis of individual patient data from 12 registration studies for the indication acute manic episode of bipolar disorder. Patients (n = 3207) were classified into one of three geographic regions: Europe (n = 981), USA (n = 1270), and other regions (n = 956). Primary outcome measures were mean symptom change score on the Young Mania Rating Scale (YMRS) from baseline to endpoint and responder status (50% improvement form baseline). Effect sizes were significantly smaller in the USA (g = 0.203, 95% confidence interval (CI) 0.062-0.344; odds ratio (OR) 1.406, 95% CI 0.998-1.980) than in Europe (g = 0.476, 95% CI 0.200-0.672; OR 2.380, 95% CI 1.682-3.368) or other regions (g = 0.533, 95% CI 0.399-0.667; OR 2.300, 95% CI 1.800-2.941). Regional differences in age, gender, initial severity, body mass index, placebo response, discontinuation rate, and type of compound could not explain the geographic differences in effect. Less severe symptoms at baseline in the US patients did explain some of the difference in responder status between patients in Europe and the USA. These findings suggest that the results of studies involving patients with acute mania cannot be extrapolated across geographic regions. Similar findings have been identified in schizophrenia, contraceptive, and in cardiovascular trials. Therefore, this finding may indicate a more general problem regarding the generalizability of pharmacological trials over geographic regions. PMID:26038109

  19. Randomized, Double-Blind, Placebo-Controlled, Safety and Immunogenicity Study of 4 Formulations of Anthrax Vaccine Adsorbed Plus CPG 7909 (AV7909) in Healthy Adult Volunteers

    PubMed Central

    Hopkins, Robert J.; Daczkowski, Nancy F.; Kaptur, Paulina E.; Muse, Derek; Sheldon, Eric; LaForce, Craig; Sari, Suha; Rudge, Thomas L.; Bernton, Edward

    2013-01-01

    A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting. This Phase 1 study compared the safety and immunogenicity of 2 IM doses (Days 0 and 14) of 4 formulations of AV7909 (AVA plus CPG 7909) with 2 IM doses of BioThrax® (Anthrax Vaccine Adsorbed) and 2 IM doses of saline placebo administered on Days 0 and 14. A total of 105 healthy adults 18 to 50 years of age were randomized to 1 of 6 study groups: BioThrax (0.5 mL), AV7909 Formulation 1 (0.5 mL AVA + 0.5 mg CPG 7909), AV7909 Formulation 2 (0.5 mL AVA + 0.25 mg CPG 7909), AV7909 Formulation 3 (0.25 mL AVA + 0.5 mg CPG 7909), AV7909 Formulation 4 (0.25 mL AVA + 0.25 mg CPG 7909), or saline placebo (0.5 mL). All randomized subjects received at least 1 vaccination, and 100 subjects completed the trial. After 2 doses, mean peak normalized toxin neutralizing antibody responses (TNA NF50) in the AV7909 groups were higher than in the BioThrax group. Differences among the 4 AV7909 groups were not statistically significant. Subjects who received AV7909 reached peak titers on Day 28 vs. Day 35 in the BioThrax group. The most common adverse events (AEs) in the BioThrax and AV7909 groups assessed as related to vaccination were injection site reactions. Transient lymphopenia was observed after the first dose in each AV7909 group. Frequencies of injection site and systemic reactions recorded by subjects in diaries for 7 days after each injection were highest with AV7909 Formulation 1. No AEs of special interest (autoimmune events) were observed in the study. Further studies of doses and dosing regimens are planned to assess the immunogenicity and reactogenicity of AV7909. PMID:23701746

  20. 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

  1. 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

  2. An oral preparation of Lactobacillus acidophilus for the treatment of uncomplicated acute watery diarrhoea in Vietnamese children: study protocol for a multicentre, randomised, placebo-controlled trial

    PubMed Central

    2013-01-01

    Background Diarrhoeal disease is a major global health problem, particularly affecting children under the age of 5 years. Besides oral rehydration solution, probiotics are also commonly prescribed to children with acute watery diarrhoea in some settings. Results from randomised clinical trials (RCTs) in which investigators studied the effect of probiotics on diarrhoeal symptoms have largely shown a positive effect; yet, the overall quality of the data is limited. In Vietnam, probiotics are the most frequently prescribed treatment for children hospitalised with acute watery diarrhoea, but there is little justification for this treatment in this location. We have designed a RCT to test the hypothesis that an oral preparation of Lactobacillus acidophilus is superior to placebo in the treatment of acute watery diarrhoea in Vietnamese children. Methods This RCT was designed to study the effect of treatment with L. acidophilus (4 × 109 colony-forming units/day) for 5 days for acute watery diarrhoea against a placebo in 300 children ages 9 to 60 months admitted to hospitals in Vietnam. Clinical and laboratory data plus samples will be collected on admission, daily during hospitalisation, at discharge, and at follow-up visits for a subset of participants. The primary end point will be defined as the time from the first dose of study medication to the start of the first 24-hour period without diarrhoea as assessed by the on-duty nurse. Secondary endpoints include the time to cessation of diarrhoea as recorded by parents or guardians in an hourly checklist, stool frequency over the first 3 days, treatment failure, rotavirus and norovirus viral loads, and adverse events. Discussion The existing evidence for the use of probiotics in treating acute watery diarrhoea seems to favour their use. However, the size of the effect varies across publications. An array of different probiotic organisms, doses, treatment durations, study populations, designs, settings, and aetiologies

  3. Topical niacinamide 4% and desonide 0.05% for treatment of axillary hyperpigmentation: a randomized, double-blind, placebo-controlled study

    PubMed Central

    Castanedo-Cazares, Juan Pablo; Lárraga-Piñones, Gabryela; Ehnis-Pérez, Adriana; Fuentes-Ahumada, Cornelia; Oros-Ovalle, Cuauhtemoc; Smoller, Bruce R; Torres-Álvarez, Bertha

    2013-01-01

    Background Axillary hyperpigmentation is a frequent cause of cosmetic consultations in dark-skinned women from tropical areas, including Latin America. Currently, there is no widely accepted treatment for the disorder, but it is usually treated with bleaching agents because it is considered a variant of inflammatory hyperpigmentation. The purpose of this study was to assess the efficacy of niacinamide 4% and desonide 0.05% emulsions compared with placebo in the treatment of axillary hyperpigmentation. Methods Twenty-four women aged 19–27 years with hyperpigmented axillae (phototype III–V) were randomly assigned to receive the study treatments in the axillary region. Improvement was assessed at baseline, then clinically and by colorimetry 9 weeks later. Quantitative evaluation including melanin, inflammatory infiltrates, NKI/Beteb, CD1a, CD68, and collagen type IV content was performed by histochemistry and immunohistochemistry, assisted by computerized morphometric analysis. Results Both niacinamide and desonide induced significant colorimetric improvement compared with placebo; however, desonide showed a better depigmenting effect than niacinamide. A good to excellent response was achieved in 24% of cases for niacinamide, 30% for desonide, and 6% for placebo. We observed a marked disruption of the basal membrane in axillary hyperpigmentation and an inflammatory infiltrate that improved after treatment. Decreased pigmentation in the desonide-treated axillae was associated with recovery of disruption at the basal membrane. Conclusion Niacinamide and desonide showed depigmenting properties in women with axillary hyperpigmentation. These findings may be explained by their antimelanogenic and anti-inflammatory properties, respectively. PMID:23355788

  4. A randomized, double-blind placebo-controlled study on acceptability, safety and efficacy of oral administration of sacha inchi oil (Plukenetia volubilis L.) in adult human subjects.

    PubMed

    Gonzales, Gustavo F; Gonzales, Carla

    2014-03-01

    The study was designed to assess acceptability and side-effects of consumption of sacha inchi oil, rich in α-linolenic acid and sunflower oil, rich in linoleic acid, in adult human subjects. Thirty subjects received 10 or 15ml daily of sacha inchi or sunflower oil for 4months. Acceptability was assessed with daily self-report and with a Likert test at the end of the study. Safety was assessed with self- recording of side-effects and with hepatic and renal markers. Primary efficacy variables were the change in lipid profile. Subjects reported low acceptability of sacha inchi oil at week-1 (37.5%). However, since week-6, acceptability was significantly increased to 81.25-93.75%. No differences were observed in acceptability with respect to sex or oil volume (P>0.05). Most frequent adverse effects during first weeks of consuming sacha inchi oil or sunflower oil were nauseas. The side-effects were reduced with time. Biochemical markers of hepatic and kidney function were maintained unchanged. Serum total cholesterol and LDL cholesterol levels and arterial blood pressure were lowered with both oils (P<0.05). Higher HDL-cholesterol was observed with sacha inchi oil at month-4. In conclusion, sacha inchi oil consumed has good acceptability after week-1 of consumption and it is safety. PMID:24389453

  5. A randomized placebo-controlled study on the effects of lutein and zeaxanthin on visual processing speed in young healthy subjects.

    PubMed

    Bovier, Emily R; Hammond, Billy R

    2015-04-15

    Speed of processing is a particularly important characteristic of the visual system. Often a behavioral reaction to a visual stimulus must be faster than the conscious perception of that stimulus, as is the case with many sports (e.g., baseball). Visual psychophysics provides a relatively simple and precise means of measuring visual processing speed called the temporal contrast sensitivity function (tCSF). Past study has shown that macular pigment (a collection of xanthophylls, lutein (L), meso-zeaxanthin (MZ) and zeaxanthin (Z), found in the retina) optical density (MPOD) is positively correlated with the tCSF. In this study, we found similar correlations when testing 102 young healthy subjects. As a follow-up, we randomized 69 subjects to receive a placebo (n=15) or one of two L and Z supplements (n=54). MPOD and tCSF were measured psychophysically at baseline and 4months. Neither MPOD nor tCSF changed for the placebo condition, but both improved significantly as a result of supplementation. These results show that an intervention with L and Z can increase processing speed even in young healthy subjects. PMID:25483230

  6. Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase.

    PubMed

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

    2011-04-01

    Depression is common in schizophrenia and worsens its course. The role of antidepressants for schizophrenic depression remains unclear. In this study, the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent randomized controlled trial. Patients (n = 41) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics were treated with add-on mirtazapine 30 mg or placebo during a 6-week double-blind phase and with open-label add-on mirtazapine during a 6-week extension phase. Efficacy measures were the Calgary Depression Scale for Schizophrenia (CDSS) and the Positive and Negative Syndrome Scale depression item. During the double-blind phase, both measures' scores decreased significantly in the mirtazapine group but not in the placebo group (for the CDSS, 52.0% vs 19.6%, respectively). During the open‐label phase, both groups demonstrated significant improvements. In between‐group comparison, a trend favoring mirtazapine did not reach statistical significance. The changes in the CDSS correlated positively with those in the Positive and Negative Syndrome Scale negative, positive and total (sub)scales for mirtazapine‐treated patients during the double‐blind phase. Depressed patients with schizophrenia may benefit from mirtazapine–first‐generation antipsychotics combination, with no increased risk for psychosis. However, more studies are needed. PMID:21469215

  7. Green tea extract decreases starch digestion and absorption from a test meal in humans: a randomized, placebo-controlled crossover study

    PubMed Central

    Lochocka, Klaudia; Bajerska, Joanna; Glapa, Aleksandra; Fidler-Witon, Ewa; Nowak, Jan K.; Szczapa, Tomasz; Grebowiec, Philip; Lisowska, Aleksandra; Walkowiak, Jaroslaw

    2015-01-01

    Green tea is known worldwide for its beneficial effects on human health. However, objective data evaluating this influence in humans is scarce. The aim of the study was to assess the impact of green tea extract (GTE) on starch digestion and absorption. The study comprised of 28 healthy volunteers, aged 19 to 28 years. In all subjects, a starch 13C breath test was performed twice. Subjects randomly ingested naturally 13C-abundant cornflakes during the GTE test (GTE 4 g) or placebo test. The cumulative percentage dose recovery (CPDR) was significantly lower for the GTE test than for the placebo test (median [interquartile range]: 11.4% [5.5–15.5] vs. 16.1% [12.7–19.5]; p = 0.003). Likewise, CPDR expressed per hour was considerably lower in each point of the measurement. In conclusion, a single dose of green tea extract taken with a test meal decreases starch digestion and absorption. PMID:26226166

  8. The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, Phase III study in patients with myelofibrosis

    PubMed Central

    Verstovsek, Srdan; Mesa, Ruben A.; Gotlib, Jason; Levy, Richard S.; Gupta, Vikas; DiPersio, John F.; Catalano, John V.; Deininger, Michael; Miller, Carole; Silver, Richard T.; Talpaz, Moshe; Winton, Elliott F.; Harvey, Jimmie H.; Arcasoy, Murat O.; Hexner, Elizabeth; Lyons, Roger M.; Paquette, Ronald; Raza, Azra; Vaddi, Kris; Erickson-Viitanen, Susan; Sun, William; Sandor, Victor; Kantarjian, Hagop M.

    2014-01-01

    Summary Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100–200 × 109/l, >200 × 109/l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan–Meier method according to original randomization group. In ruxolitinib-treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I. PMID:23480528

  9. AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study

    PubMed Central

    Thomas, Michael; Sheran, Jane; Smith, Natalie; Fonseca, Sofia; Lee, Amanda J

    2007-01-01

    Background Despite effective treatments, asthma outcomes remain suboptimal. Interest exists in complementary therapies, particularly in herbal remedies for asthma treatment, currently with inconclusive evidence of efficacy. The encapsulated botanical mixture AKL1 has anecdotal evidence of effectiveness in asthma. Methods We performed a randomised controlled cross over study comparing the effectiveness of AKL1 with indistinguishable placebo as add-on therapy in patients uncontrolled on standard asthma treatment. Thirty two adult asthmatics completed a 36 week trial consisting of a 4 week single blind run in period, during which placebo was added to usual treatment, a 12 week double blind active phase in which subjects received AKL1 or placebo, a single blind 8 week washout period receiving placebo and a final 12 week double blind cross-over active treatment phase. Daily diaries were kept of peak expiratory flow and symptoms, and spirometry, validated symptom and health status questionnaire scores and adverse events were monitored at study visits. Paired T tests were used to compare the effects of placebo and AKL1 on outcomes. Changes in outcome measures over treatment phases are presented as means and 95% confidence intervals (CI) of means. Results No significant differences in lung function (active-placebo) were found (Forced Expiratory Volume in 1 second: mean difference [95% CI] = 0.01 [-0.12 to 0.14] L, p = 0.9. Peak Expiratory Flow: -4.08 [-35.03 to 26.89]. L/min, p = 0.8). Trends to clinical improvements favouring active treatment were however consistently seen in the patient-centered outcomes: Asthma Control Questionnaire mean difference (active – placebo) [95% CI] = -0.35 [-0.78 to 0.07], p = 0.10, Asthma Quality of Life Questionnaire mean difference 0.42 [-0.08 to 0.93], p = 0.09, Leicester Cough Questionnaire mean difference 0.49, [-0.18 to 1.16], p = 0.15. Nine exacerbations occurred during placebo treatment and five whilst on AKL1. No significant

  10. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study

    PubMed Central

    2014-01-01

    Background Recent studies have demonstrated that mesenchymal stem cells (MSCs) modulate the immune response and reduce lung injury in animal models. Currently, no clinical studies of the effects of MSCs in acute respiratory distress syndrome (ARDS) exist. The objectives of this study were first to examine the possible adverse events after systemic administration of allogeneic adipose-derived MSCs in ARDS patients and second to determine potential efficacy of MSCs on ARDS. Methods Twelve adult patients meeting the Berlin definition of acute respiratory distress syndrome with a PaO2/FiO2 ratio of < 200 were randomized to receive allogeneic adipose-derived MSCs or placebo in a 1:1 fashion. Patients received one intravenous dose of 1 × 106 cells/kg of body weight or saline. Possible side effects were monitored after treatment. Acute lung injury biomarkers, including IL-6, IL-8 and surfactant protein D (SP-D), were examined to determine the effects of MSCs on lung injury and inflammation. Results There were no infusion toxicities or serious adverse events related to MSCs administration and there were no significant differences in the overall number of adverse events between the two groups. Length of hospital stay, ventilator-free days and ICU-free days at day 28 after treatment were similar. There were no changes in biomarkers examined in the placebo group. In the MSCs group, serum SP-D levels at day 5 were significantly lower than those at day 0 (p = 0.027) while the changes in IL-8 levels were not significant. The IL-6 levels at day 5 showed a trend towards lower levels as compared with day 0, but this trend was not statistically significant (p = 0.06). Conclusions Administration of allogeneic adipose-derived MSCs appears to be safe and feasible in the treatment of ARDS. However, the clinical effect with the doses of MSCs used is weak, and further optimization of this strategy will probably be required to reach the goal of reduced alveolar epithelial

  11. 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

  12. Meta-analysis of randomized, double-blind, placebo-controlled, efficacy and safety studies of mirtazapine versus amitriptyline in major depression.

    PubMed

    Stahl, S; Zivkov, M; Reimitz, P E; Panagides, J; Hoff, W

    1997-01-01

    A meta-analysis was performed on efficacy and safety data from 4 randomized, double-blind, 6-week, single-center studies comparing mirtazapine (n = 194; 5-35 mg/day) with amitriptyline (n = 193, 40-280 mg/day) and placebo (n = 193) in outpatients with a DSM-III diagnosis of major depressive episode. On all the main efficacy variables both active drugs consistently produced significantly greater improvements and significantly greater percentages of responders or remitters than placebo. The meta-analysis of adverse events shows that mirtazapine was better tolerated than amitriptyline, particularly with respect to anticholinergic and cardiac adverse events. There were no differences between mirtazapine and placebo regarding the incidence of serotonergic adverse events. In conclusion, the results of this meta-analysis demonstrate that mirtazapine is as effective as amitriptyline but has a better tolerability profile. PMID:9265948

  13. Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study

    PubMed Central

    Satoh, Jo; Kohara, Nobuo; Sekiguchi, Kenji; Yamaguchi, Yasuyuki

    2016-01-01

    We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P = 0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P = 0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). PMID:26881251

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

    PubMed Central

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

    2014-01-01

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

  15. Subjective and Cardiovascular Effects of Intravenous Methamphetamine during Perindopril Maintenance: A Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

    PubMed Central

    Haile, Colin N.; De La Garza, Richard; Grasing, Kenneth; Kosten, Thomas R.; Newton, Thomas F.

    2016-01-01

    Background: Our pilot study suggested that the angiotensin-converting enzyme inhibitor perindopril might reduce some subjective effects produced by i.v. methamphetamine. We characterized the impact of a wider range of perindopril doses on methamphetamine-induced effects in a larger group of non-treatment-seeking, methamphetamine-using volunteers. Methods: Before treatment, participants received 30mg methamphetamine. After 5 to 7 days of perindopril treatment (0, 4, 8, or 16mg/d), participants received 15 and 30mg of methamphetamine on alternate days. Before and after treatment, participants rated subjective effects and cardiovascular measures were collected. Results: Prior to treatment with perindopril, there were no significant differences between treatment groups on maximum or peak subjective ratings or on peak cardiovascular effects. Following perindopril treatment, there were significant main effects of treatment on peak subjective ratings of “anxious” and “stimulated”; compared to placebo treatment, treatment with 8mg perindopril significantly reduced peak ratings of both anxious (P=.0009) and stimulated (P=.0070). There were no significant posttreatment differences between groups on peak cardiovascular effects. Conclusions: Moderate doses of perindopril (8mg) significantly reduced peak subjective ratings of anxious and stimulated as well as attenuated many other subjective effects produced by methamphetamine, likely by inhibiting angiotensin II synthesis. Angiotensin II is known to facilitate the effects of norepinephrine, which contributes to methamphetamine’s subjective effects. The lack of a classic dose-response function likely results from either nonspecific effects of perindopril or from between-group differences that were not accounted for in the current study (i.e., genetic variations and/or caffeine use). The current findings suggest that while angiotensin-converting enzyme inhibitors can reduce some effects produced by methamphetamine

  16. GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.

    PubMed

    Besson, Marie; Matthey, Alain; Daali, Youssef; Poncet, Antoine; Vuilleumier, Pascal; Vuillemier, Pascal; Curatolo, Michele; Zeilhofer, Hanns Ulrich; Desmeules, Jules

    2015-03-01

    Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain. Tolterodine (TLT) was used as an active placebo. The primary outcome parameter was a change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH), which was monitored for 8 hours after drug application. Sedative effects were assessed in parallel to antihyperalgesia. Compared with TLT, recovery from hyperalgesia was significantly faster in the CBZ and CLN groups (P = 0.009). At the time point of maximum effect, the rate of recovery from hyperalgesia was accelerated by CBZ and CLN, relative to placebo by 15.7% (95% confidence interval [CI] 0.8-30.5), P = 0.040, and 28.6% (95% CI 4.5-52.6), P = 0.022, respectively. Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity. PMID:25687539