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Sample records for 12-week multicenter double-blind

  1. A 12-Week Double-Blind, Placebo-Controlled, Flexible-Dose Trial of Vilazodone in Generalized Social Anxiety Disorder

    PubMed Central

    Careri, Jason M.; Draine, Ann E.; Hanover, Rita; Liebowitz, Michael R.

    2015-01-01

    Objective: To examine the efficacy, safety, and tolerability of vilazodone for subjects (aged 18–75 years) with generalized social anxiety disorder. Method: Forty-four subjects with generalized social anxiety disorder (DSM-IV-TR criteria) were randomized to vilazodone or placebo in a 12-week double-blind, flexible-dose trial. Change from baseline to endpoint on the Liebowitz Social Anxiety Scale (LSAS) was the primary outcome measure. Secondary outcome measures included response and remission rates and changes in depression and anxiety. Data were collected between November 2012 and April 2014. The study was conducted at a private clinical trials facility in New York, New York. Results: The mean baseline LSAS score was 91.9 (SD = 17.5) and the mean Clinical Global Impressions–Severity scale score was 5.3 (SD = 0.56), indicating marked to severe illness. There were no significant baseline differences in severity of social anxiety between the treatment groups. At the end of treatment, in the intent-to-treat sample (n = 39), the vilazodone group had improved significantly more than the placebo group by 14.3 points on the LSAS (t = 1.80, P = .04, one-tail test) (Cohen d = 0.58). Conclusions: The findings suggest that vilazodone may be a promising treatment for social anxiety disorder. Further study is needed given the limited sample size. Trial Registration: ClinicalTrials.gov identifier: NCT01712321 PMID:27057414

  2. Magnesium Replacement Does Not Improve Insulin Resistance in Patients With Metabolic Syndrome: A 12-Week Randomized Double-Blind Study

    PubMed Central

    Lima de Souza e Silva, Maria de Lourdes; Cruz, Thomaz; Rodrigues, Luiz Erlon; Ladeia, Ana Marice; Bomfim, Olivia; Olivieri, Lucas; Melo, Juliana; Correia, Raquel; Porto, Mirna; Cedro, Alexandre

    2014-01-01

    Background To evaluate the effect of magnesium (Mg) replacement on insulin resistance and cardiovascular risk factors in women with metabolic syndrome (MS) without diabetes. Methods This 12-week clinical randomized double-blind study compared the effects of 400 mg/day of Mg with those of a placebo (n = 72) on fasting glucose, insulin, HOMA-IR, lipid profile and CRP. Mg was measured in serum (SMg) and in mononuclear cells (MMg). Results Hypomagnesemia (SMg < 1.7 mg/dL) was seen in 23.2% of patients and intracellular depletion in 36.1% of patients. The MMg means were lower in patients with obesity (0.94 ± 0.54 μg/mg vs. 1.19 ± 0.6 μg/mg, P = 0.04), and insulin resistance (0.84 ± 0.33 μg/mg vs. 1.14 ± 0.69 µg/mg, P < 0.05). Mg replacement did not alter SMg (1.82 ± 0.14 mg/dL vs. 1.81 ± 0.16 mg/dL, P = 0.877) and tended to increment MMg (0.90 ± 0.40 μg/mg vs. 1.21 ± 0.73 μg/mg, P = 0.089). HOMA-IR did not alter in interventions nor in placebo group (3.2 ± 2.0 to 2.8 ± 1.9, P = 0.368; 3.6 ± 1.9 to 3.2 ± 1.8, respectively), neither did other metabolic parameters. Conclusion Serum and intracellular Mg depletion is common in patients with MS; however, Mg replacement in recommended dosage did not increase significantly Mg levels, neither reduced insulin resistance or metabolic control. PMID:25247020

  3. Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial

    PubMed Central

    Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2015-01-01

    Low-dose memantine might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. We investigated whether add-on memantine reduced cytokine levels and benefitted patients with opioid dependence undergoing methadone maintenance therapy (MMT) in a randomized, double-blind, controlled 12-week study. Patients were randomly assigned to a group: Memantine (5 mg/day) (n = 53) or Placebo (n = 75). The methadone dose required and retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor (TGF)-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower methadone dose than did Placebo-group (P = 0.039). They also had significantly lower plasma TNF-α and significantly higher TGF-β1 levels. We provide evidence of the benefit of add-on memantine in opioid dependent patients undergoing MMT. PMID:25988317

  4. [Optimized interval treatment of eczema with fluprednidene. A multicenter double-blind study].

    PubMed

    Mahrle, G; Wemmer, U; Matthies, C

    1989-09-15

    In a multicenter double-blind study, 44 patients suffering from eczema were bilaterally treated with 0.1% fluprednidene-21-acetate over 21 days. Continuous application twice a day was compared with intermittent therapy, i.e. 1 day intermission (15 patients), 2 days intermission (16 patients) and 3 days intermission (13 patients) using the cream base. Final evaluation was based on 11 criteria. All regimens, continuous and intermittent, proved effective (at least 90% reduction of the lesions). Treatment with 3 days intermission showed the same favorable results as continuous application, although the amount of glucocorticoids applied was 75% less. Measurements of the skin fold thickness (SFT) in healthy controls did not indicate any atrophy after treatment with fluprednidene under the same conditions as the eczema patients or under occlusion for up to 21 days. Clobetasol-17-propionate, in contrast, significantly reduced the SFT already after application of only 1 week. PMID:2683439

  5. The effect of 12 weeks Anethum graveolens (dill) on metabolic markers in patients with metabolic syndrome; a randomized double blind controlled trial

    PubMed Central

    2012-01-01

    Background The clustering of metabolic abnormalities defined as metabolic syndrome is now both a public health and a clinical problem .While interest in herbal medicine has greatly increased, lack of human evidence to support efficacies shown in animals does exist. This clinical trial study designed to investigate whether herbal medicine, Anethum graveolens (dill) extract, could improve metabolic components in patients with metabolic syndrome. Methods A double-blind, randomized, placebo-controlled trial using a parallel design was conducted. 24 subjects who had metabolic syndrome diagnostic criteria (update of ATP III) were randomly assigned to either dill extract (n = 12) or placebo (n = 12) for 3 months. Results Across lipid component of metabolic syndrome, no significant differences in triglyceride (TG) concentration and high density lipoprotein cholesterol were seen between the two groups. However TG improved significantly from baseline (257.0 vs. 201.5p = 0.01) with dill treatment but such a significant effect was not observed in placebo group. Moreover, no significant differences in waist circumference, blood pressure and fasting blood sugar were seen between two groups after 3 months follow up period. Conclusion In this small clinical trial in patients with metabolic syndrome, 12 weeks of dill extract treatment had a beneficial effect in terms of reducing TG from baseline. However dill treatment was not associated with a significant improvement in metabolic syndrome related markers compared to control group. Larger studies might be required to prove the efficacy and safety of long-term administration of dill to resolve metabolic syndrome components. PMID:23351341

  6. 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

  7. Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study.

    PubMed

    Puhl, W; Bernau, A; Greiling, H; Köpcke, W; Pförringer, W; Steck, K J; Zacher, J; Scharf, H P

    1993-10-01

    The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each group were excluded from the protocol-correct efficacy analysis. The Lequesne Index, the first main criterion, showed a significant superiority of the verum-treated patients after the third injection up to the final follow-up examination 9 weeks after the last injection (MANOVA, P < 0.025). The consumption of paracetamol was defined as a complementary main criterion that did not reveal significant differences between the treatment groups. Most of the individual secondary endpoints demonstrated a much better response to the active treatment without reaching the significance level in the intergroup comparisons for the single time-points. Side-effects were confined to local reactions of minor severity and short duration in four patients (six events) of the verum group and in five patients of the control group. Clinical chemistry and hematology remained essentially unchanged. PMID:15449510

  8. Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients.

    PubMed

    Cohn, C K; Shrivastava, R; Mendels, J; Cohn, J B; Fabre, L F; Claghorn, J L; Dessain, E C; Itil, T M; Lautin, A

    1990-12-01

    Two hundred forty-one elderly depressed patients entered the 8-week, double-blind phase of this parallel-group, multicenter study; 161 patients were randomized to receive sertraline (50-200 mg/day) and 80 were randomized to receive amitriptyline (50-150 mg/day). Among evaluable patients, there were no statistically significant differences between treatments in any of the primary efficacy variables: change in total Hamilton Rating Scale for Depression (HAM-D) score (17 items), percentage change in HAM-D score, change in HAM-D Item 1, change in Clinical Global Impressions (CGI) Severity score, change in the Depression Factor of the 56-item Hopkins Symptom Checklist, and the CGI Improvement score at the last visit. Similar results were obtained using data from all patients (intention-to-treat analysis), except that amitriptyline was superior in HAM-D Total score (p = .044). The two drugs produced a similar degree of response: on the basis of the HAM-D criterion, 69.4% of sertraline patients and 62.5% of amitriptyline patients responded, and, on the basis of CGI criterion, 79.5% of sertraline and 73.4% of amitriptyline patients responded. Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5% (4) because of a laboratory abnormality. In comparison, 35% of the amitriptyline patients withdrew because of treatment-related side effects. Sertraline was associated with a statistically lower frequency of somnolence, dry mouth, constipation, ataxia, and pain and a higher frequency of nausea, anorexia, diarrhea/loose stools, and insomnia; thus, anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2258379

  9. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial

    PubMed Central

    Rossignol, Daniel A; Rossignol, Lanier W; Smith, Scott; Schneider, Cindy; Logerquist, Sally; Usman, Anju; Neubrander, Jim; Madren, Eric M; Hintz, Gregg; Grushkin, Barry; Mumper, Elizabeth A

    2009-01-01

    Background Several uncontrolled studies of hyperbaric treatment in children with autism have reported clinical improvements; however, this treatment has not been evaluated to date with a controlled study. We performed a multicenter, randomized, double-blind, controlled trial to assess the efficacy of hyperbaric treatment in children with autism. Methods 62 children with autism recruited from 6 centers, ages 2–7 years (mean 4.92 ± 1.21), were randomly assigned to 40 hourly treatments of either hyperbaric treatment at 1.3 atmosphere (atm) and 24% oxygen ("treatment group", n = 33) or slightly pressurized room air at 1.03 atm and 21% oxygen ("control group", n = 29). Outcome measures included Clinical Global Impression (CGI) scale, Aberrant Behavior Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC). Results After 40 sessions, mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0008), receptive language (p < 0.0001), social interaction (p = 0.0473), and eye contact (p = 0.0102); 9/30 children (30%) in the treatment group were rated as "very much improved" or "much improved" compared to 2/26 (8%) of controls (p = 0.0471); 24/30 (80%) in the treatment group improved compared to 10/26 (38%) of controls (p = 0.0024). Mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0336), receptive language (p = 0.0168), and eye contact (p = 0.0322). On the ABC, significant improvements were observed in the treatment group in total score, irritability, stereotypy, hyperactivity, and speech (p < 0.03 for each), but not in the control group. In the treatment group compared to the control group, mean changes on the ABC total score and subscales were similar except a greater number of children improved in irritability (p = 0.0311). On the ATEC, sensory/cognitive awareness significantly improved (p = 0.0367) in the treatment group

  10. 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

  11. 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

  12. Efficacy of the long-acting nitro vasodilator pentaerithrityl tetranitrate in patients with chronic stable angina pectoris receiving anti-anginal background therapy with beta-blockers: a 12-week, randomized, double-blind, placebo-controlled trial

    PubMed Central

    Münzel, Thomas; Meinertz, Thomas; Tebbe, Ulrich; Schneider, Heinrich Theodor; Stalleicken, Dirk; Wargenau, Manfred; Gori, Tommaso; Klingmann, Ingrid

    2014-01-01

    Background The organic nitrate pentaerithrityl tetranitrate (PETN) has been shown to have ancillary properties that prevent the development of tolerance and endothelial dysfunction. This randomized, double-blind, placebo-controlled, multicentre study (‘CLEOPATRA’ study) was designed to investigate the anti-ischaemic efficacy of PETN 80 mg b.i.d. (morning and mid-day) over placebo in patients with chronic stable angina pectoris. Methods and results A total of 655 patients were evaluated in the intention-to-treat population, randomized to PETN (80 mg b.i.d., n = 328) or placebo (n = 327) and completed the study. Patients underwent treadmill exercise tests at randomization, after 6 and 12 weeks of treatment. Treatment with PETN over 12 weeks did not modify the primary endpoint total exercise duration (TED, P = 0.423). In a pre-specified sub-analysis of patients with reduced exercise capacity (TED at baseline ≤9 min, n = 257), PETN appeared more effective than placebo treatment (P = 0.054). Superiority of PETN over placebo was evident in patients who were symptomatic at low exercise levels (n = 120; P = 0.017). Pentaerithrityl tetranitrate 80 mg b.i.d. was well tolerated, and the overall safety profile was comparable with placebo. Conclusion Although providing no additional benefit in unselected patients with known coronary artery disease, PETN therapy, administered in addition to modern anti-ischaemic therapy, could increase exercise tolerance in symptomatic patients with reduced exercise capacity. PMID:24071762

  13. A Double-Blind, 12-Week Study to Evaluate the Antiaging Efficacy of a Cream Containing the NFκB Inhibitor 4-Hexyl-1, 3-Phenylenediol and Ascorbic Acid-2 Glucoside in Adult Females.

    PubMed

    Roure, Romain; Nollent, Virginie; Dayan, Liliane; Camel, Etienne; Bertin, Christiane

    2016-06-01

    The 5 main physical manifestations of aged skin are wrinkles, uneven tone, brown spots, loss of elasticity, and dryness. One mechanism resulting in these physical manifestations is increased activity of the nuclear factor kappa B (NFκB) protein. This 12-week, double-blind, placebo-controlled, randomized split-face study compared the antiaging effect and safety of a face cream containing 4-Hexyl-1, 3-phenylenediol, an NFκB inhibitor, and ascorbic acid-2 glucoside versus placebo in adult females aged 45-70 years old. Subjects (n=42) applied active treatment or placebo to the same half face twice daily at home for 12 weeks. Clinical evaluation was carried out by a dermatologist. Subjects carried out similar self-grading assessments. Colorimetric measurements analyzed skin color, and biomechanical skin properties were evaluated. Clinical grading showed that most wrinkle parameters were significantly improved after 8 weeks of active treatment compared with baseline and placebo (P≤.05), with improvements maintained after 12 weeks. Only Marionette wrinkles did not show a significant improvement. Brown spots (color intensity/number), overall photodamage, and most complexion parameters improved significantly after 8 and 12 weeks compared with baseline and placebo (P≤.05). Self-grading yielded similar results compared with baseline. Self-grading did not demonstrate improvements with active treatment versus placebo, except for skin firmness at 8 and 12 weeks (P≤.05). A significant difference was seen with active treatment compared with placebo in all colorimetric parameters (L*, b*, and ITA°) after 8 weeks, and in spot coloration (b*) after 12 weeks (P<.05). Improvements in skin elasticity were not significantly different between treatments. Overall tolerability of active treatment was judged as good. In conclusion, a cream containing 4-Hexyl-1, 3-phenylenediol and ascorbic acid-2 glucoside improves the clinical appearance of aged

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2011-01-01

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

  16. 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

  17. Effect of ginger powder supplementation on nitric oxide and C-reactive protein in elderly knee osteoarthritis patients: A 12-week double-blind randomized placebo-controlled clinical trial.

    PubMed

    Naderi, Zahra; Mozaffari-Khosravi, Hassan; Dehghan, Ali; Nadjarzadeh, Azadeh; Huseini, Hassan Fallah

    2016-07-01

    There is limited evidence that ginger ( shēng jiāng) powder consumption can relieve pain and inflammation because of its special phytochemical properties. This study is aimed at investigating the effect of ginger powder supplementation on some inflammatory markers in patients suffering from knee osteoarthritis. This is a double-blind randomized placebo-controlled clinical trial with a follow-up period of 3 months that was conducted on 120 outpatients with moderately painful knee osteoarthritis. Patients were randomly divided up into two groups: ginger group (GG) or placebo group (PG). Both groups received two identical capsules on a daily basis for 3 months. Each ginger capsule contained 500 mg of ginger powder; the placebo capsules had 500 mg of starch in them. Serum samples were collected prior to and after the intervention and were stored at -70 °C until the end of the study. Serum concentration of nitric oxide (NO) and hs-C reactive protein (hs-CRP) were measured using enzyme-linked immunosorbent assay kits. There was no significant difference between the two groups in terms of inflammatory markers (i.e., NO and hs-CRP) prior to the intervention. However, after 3 months of supplementation, serum concentration of NO and hs-CRP decreased in the GG. After 12 weeks, the concentration of these markers declined more in the GG than in the PG. Ginger powder supplementation at a dose of 1 g/d can reduce inflammatory markers in patients with knee osteoarthritis, and it thus can be recommended as a suitable supplement for these patients. PMID:27419081

  18. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study

    PubMed Central

    Takeuchi, Tsutomu; Tanaka, Yoshiya; Iwasaki, Manabu; Ishikura, Hiroaki; Saeki, Satoshi; Kaneko, Yuichiro

    2016-01-01

    Objective To evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA). Methods In a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12. Results Mean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg). Conclusions Treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment. Trial registration number NCT01649999; Results. PMID:26672064

  19. Cardiovascular, renal and gastrointestinal effects of incretin-based therapies: an acute and 12-week randomised, double-blind, placebo-controlled, mechanistic intervention trial in type 2 diabetes

    PubMed Central

    Smits, Mark M; Tonneijck, Lennart; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Pieters, Indra C; Cahen, Djuna L; Diamant, Michaela; van Raalte, Daniël H

    2015-01-01

    Introduction Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. Methods and analyses 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention

  20. A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett’s esophagus

    PubMed Central

    Jin, Zhe; Cheng, Yulan; Gu, Wen; Zheng, Yingye; Sato, Fumiaki; Mori, Yuriko; Olaru, Alexandru V.; Paun, Bogdan C.; Yang, Jian; Kan, Takatsugu; Ito, Tetsuo; Hamilton, James P.; Selaru, Florin M.; Agarwal, Rachana; David, Stefan; Abraham, John M.; Wolfsen, Herbert C.; Wallace, Michael B.; Shaheen, Nicholas J.; Washington, Kay; Wang, Jean; Canto, Marcia Irene; Bhattacharyya, Achyut; Nelson, Mark A.; Wagner, Paul D.; Romero, Yvonne; Wang, Kenneth K.; Feng, Ziding; Sampliner, Richard E.; Meltzer, Stephen J.

    2009-01-01

    Esophageal adenocarcinoma risk in Barrett’s esophagus (BE) is increased 30- to 125-fold versus the general population. Among all BE patients, however, neoplastic progression occurs only once per 200 patient-years. Molecular biomarkers are therefore needed to risk-stratify patients for more efficient surveillance endoscopy and to improve the early detection of progression. We therefore performed a retrospective, multicenter, double-blinded validation study of 8 BE progression prediction methylation biomarkers. Progression or nonprogression were determined at 2 years (tier 1) and 4 years (tier 2). Methylation was assayed in 145 nonprogressors (NPs) and 50 progressors (Ps) using real-time quantitative methylation-specific PCR. Ps were significantly older than NPs (70.6 vs. 62.5 years, p < 0.001). We evaluated a linear combination of the 8 markers, using coefficients from a multivariate logistic regression analysis. Areas under the ROC curve (AUCs) were high in the 2-, 4-year and combined data models (0.843, 0.829 and 0.840; p<0.001, p<0.001 and p<0.001, respectively). In addition, even after rigorous overfitting correction, the incremental AUCs contributed by panels based on the 8 markers plus age vs. age alone were substantial (Δ-AUC = 0.152, 0.114 and 0.118, respectively) in all three models. A methylation biomarker-based panel to predict neoplastic progression in BE has potential clinical value in improving both the efficiency of surveillance endoscopy and the early detection of neoplasia. PMID:19435894

  1. Comparison of Iohexol-380 and Iohexol-350 for Coronary CT Angiography: A Multicenter, Randomized, Double-Blind Phase 3 Trial

    PubMed Central

    Park, Eun-Ah; Kang, Doo Kyoung; Kim, Sung Jin; Kim, Young-Ju; Kim, Yookyung; Sung, Yon Mi; Song, Soon-Young; Oh, Yu-Whan; Yong, Hwan Seok; Lee, Heon; Jeon, Eui-Yong; Jin, Gong-Yong; Choi, Byoung Wook; Choi, Sang-Il

    2016-01-01

    Objective This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. Materials and Methods Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. Results A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). Conclusion Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine. PMID:27134522

  2. Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Furuya, Motohide; Horiguchi, Jun; Hashioka, Sadayuki; Thoyama, Masaya; Murotani, Kenta; Mori, Norio; Minabe, Yoshio; Iyo, Masaomi; Ueno, Shuichi; Ezoe, Sachiko; Hoshino, Syuzo; Seno, Haruo

    2015-01-01

    Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: −0.23 ± 0.08; placebo: −0.03 ± 0.08, P < 0.018), tension (TJ-54: −0.42 ± 0.09; placebo: −0.18 ± 0.09, P < 0.045), and poor impulse control (TJ-54: −0.39 ± 0.10; placebo: −0.07 ± 0.10, P < 0.037). Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores. PMID:25954314

  3. A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine.

    PubMed

    Bartolini, Marco; Giamberardino, Maria Adele; Lisotto, Carlo; Martelletti, Paolo; Moscato, Davide; Panascia, Biagio; Savi, Lidia; Pini, Luigi Alberto; Sances, Grazia; Santoro, Patrizia; Zanchin, Giorgio; Omboni, Stefano; Ferrari, Michel D; Brighina, Filippo; Fierro, Brigida

    2011-06-01

    The objective of this study was to evaluate patients' satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1-3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment. PMID:21437714

  4. The Efficacy and Safety of Chinese Herbal Medicine Jinlida as Add-On Medication in Type 2 Diabetes Patients Ineffectively Managed by Metformin Monotherapy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial

    PubMed Central

    Lian, Fengmei; Tian, Jiaxing; Chen, Xinyan; Li, Zhibin; Piao, Chunli; Guo, Junjie; Ma, Licheng; Zhao, Lijuan; Xia, Chengdong; Wang, Chong-Zhi; Yuan, Chun-Su; Tong, Xiaolin

    2015-01-01

    Background Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. Methods A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA- β) were also evaluated. Results At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69 - 1.14 for the Jinlida group vs. 0.34 - 0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Conclusion Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Trial Registration Chinese Clinical Trial Register

  5. Multicenter, Double-Blind, Randomized, Phase 2 Study Evaluating the Novel Antibiotic Cadazolid in Patients with Clostridium difficile Infection

    PubMed Central

    Nord, Carl Erik; Talbot, George H.; Wilcox, Mark; Gerding, Dale N.; Buitrago, Martha; Kracker, Hilke; Charef, Pascal; Cornely, Oliver A.

    2015-01-01

    Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study evaluated the efficacy and safety of oral cadazolid in treatment of adult patients with C. difficile infection (CDI). Eligible patients with first occurrence/first recurrence of CDI were randomized 1:1:1:1 to 250, 500, or 1,000 mg cadazolid twice daily (BID) or oral 125 mg vancomycin four times daily (QID) for 10 days. The primary endpoint was clinical cure at test of cure (48 ± 24 h after the end of treatment; modified intent-to-treat population), defined as resolution of diarrhea with no further CDI treatment required. Secondary endpoints included recurrence rate, sustained clinical response (clinical cure without recurrence), and time to diarrhea resolution. Of 84 patients enrolled, 20, 22, 20, and 22 received 250, 500, or 1,000 mg cadazolid BID or 125 mg vancomycin QID, respectively. The primary endpoint was achieved in 76.5% (80% confidence interval [CI], 58.4, 89.3), 80.0% (63.9, 91.0), 68.4% (51.1, 82.5), and 68.2% (52.3, 81.3) of patients, respectively. There was no evidence of a cadazolid dosage-dependent response. Each dosage of cadazolid resulted in a lower recurrence rate than with vancomycin (18.2 to 25.0% versus 50%). Consequently, higher sustained clinical response rates were observed with cadazolid (46.7 to 60.0%) than with vancomycin (33.3%). The times to diarrhea resolution were similar for cadazolid and vancomycin. Cadazolid was well tolerated, with no safety signal observed. The results of this phase 2 study support further clinical development of cadazolid. (This study has been registered in the United States at ClinicalTrials.gov under registration no. NCT01222702 and in Europe with the European Medicines Agency under registration no. EUDRA-CT 2010-020941-29.) PMID:26248357

  6. Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study

    PubMed Central

    Xu, Haiyan; Gopal, Srihari; Nuamah, Isaac; Ravenstijn, Paulien; Janik, Adam; Schotte, Alain; Hough, David; Fleischhacker, Wolfgang W.

    2016-01-01

    Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. PMID:26902950

  7. A 12-week double-blind study of the efficacy, safety and tolerance of pirazolac b.i.d. compared with indomethacin t.i.d. in patients with ankylosing spondylitis.

    PubMed

    Carcassi, C; La Nasa, G; Perpignano, G

    1990-01-01

    A 12-week trial was carried out to compare the efficacy of pirazolac (300-600 mg b.i.d.) with that of indomethacin (25-50 mg t.i.d.) in patients with ankylosing spondylitis. A total of 119 patients completed the treatment period, with 32 drop-outs. Both therapies showed significant improvements in clinical symptoms. PMID:2198157

  8. Treatment of Bacterial Vaginosis: A Multicenter, Double-Blind, Double-Dummy, Randomised Phase III Study Comparing Secnidazole and Metronidazole

    PubMed Central

    Bohbot, Jean-Marc; Vicaut, Eric; Fagnen, Didier; Brauman, Michel

    2010-01-01

    Objective. Multiple-dose metronidazole oral therapy is currently the reference treatment for bacterial vaginosis (BV). This double-blind, double-dummy, noninferiority study compared the efficacy of secnidazole, another nitroimidazole with pharmacokinetics allowing a single dose regimen, to this standard treatment. Methods. A total of 577 patients were randomized to receive metronidazole (500 mg, b.i.d for seven days) or secnidazole (2 g, once). Therapeutic cure at D28 was defined as the resolution of vaginal discharge, positive KOH whiff test, vaginal pH >4.5 and Nugent score >7 on Gram-stained vaginal fluid. Results. According to this primary endpoint, the single-dose secnidazole regimen was shown to be at least as effective as the multiple-dose metronidazole regimen (60.1 % cured women vs 59.5% , 95% confidence interval with a noninferiority margin of 10%: [−0.082; 0.0094]). Safety profiles were comparable in both groups. Conclusion. The secnidazole regimen studied represents an effective, convenient therapeutic alternative that clinicians should consider in routine practice. PMID:20885970

  9. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

    PubMed Central

    2013-01-01

    Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain. PMID:23414938

  10. Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

    PubMed Central

    van Bergen, Christiaan JA; Blankevoort, Leendert; de Haan, Rob J; Sierevelt, Inger N; Meuffels, Duncan E; d'Hooghe, Pieter RN; Krips, Rover; van Damme, Geert; van Dijk, C Niek

    2009-01-01

    Background Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration Netherlands Trial Register (NTR1636) PMID:19591674

  11. Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial.

    PubMed

    Koike, Haruki; Akiyama, Kazuo; Saito, Toyokazu; Sobue, Gen

    2015-03-01

    Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease. PMID:25577176

  12. Tear volume estimation using a modified Schirmer test: a randomized, multicenter, double-blind trial comparing 3% diquafosol ophthalmic solution and artificial tears in dry eye patients

    PubMed Central

    Miyake, Hideki; Kawano, Yuri; Tanaka, Hiroshi; Iwata, Akihiro; Imanaka, Takahiro; Nakamura, Masatsugu

    2016-01-01

    Purpose We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients. Patients and methods A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests. Results According to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears. Conclusion The modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear-secreting compounds for dry eye. PMID:27257372

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

    PubMed Central

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

    2015-01-01

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

  14. Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

    PubMed

    Sabate, A; Gutierrez, R; Beltran, J; Mellado, P; Blasi, A; Acosta, F; Costa, M; Reyes, R; Torres, F

    2016-08-01

    We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin-stratified, double-blind, fibrinogen-versus-saline-controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5-63.3%) in the fibrinogen group and 42.74% (95% CI 28.3-57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57-1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements. PMID:26880105

  15. Effect of Probiotic Lactobacillus (Lacidofil® Cap) for the Prevention of Antibiotic-associated Diarrhea: A Prospective, Randomized, Double-blind, Multicenter Study

    PubMed Central

    Song, Hyun Joo; Kim, Jin-Yong; Kim, Seong-Eun; Park, Hye-Sook; Jeong, Yoolwon; Hong, Sung Pil; Cheon, Jae Hee; Kim, Won Ho; Kim, Hyo-Jong; Ye, Byong Duk; Yang, Suk-Kyun; Kim, Sang-Woo; Shin, Sung-Jae; Kim, Hyun-Soo; Sung, Jae-Kyu; Kim, Eun Young

    2010-01-01

    Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use. There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics. The aim of this multicenter, randomized, placebo-controlled, double-blind trial was to assess the efficacy of probiotic Lactobacillus (Lacidofil® cap) for the prevention of AAD in adults. From September 2008 to November 2009, a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were randomized to receive Lactobacillus (Lacidofil® cap) or placebo for 14 days. Patients recorded bowel frequency and stool consistency daily for 14 days. The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment. AAD developed in 4 (3.9%) of 103 patients in the Lactobacillus group and in 8 (7.2%) of 111 patients in the placebo group (P=0.44). However, the Lactobacillus group showed lower change in bowel frequency and consistency (50/103, 48.5%) than the placebo group (35/111, 31.5%) (P=0.01). Although the Lacidofil® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics, the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group. PMID:21165295

  16. Efficacy and Safety of “URSA Complex” in Subjects with Physical Fatigue: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

    PubMed Central

    Kim, Kwang-Min; Kim, Moon-Jong; Song, Sang-Wook; Cho, Doo-Yeoun; Park, Kyung-Chae; Yang, Sung-Won; Kim, Young-Sang; Kim, Kyung-Soo

    2016-01-01

    Background: Fatigue is a common symptom both in diseases status and in healthy subjects. Various supplements and nutraceuticals for relieving of fatigue have been used. However, there are a few studies to evaluate the efficacy and the safety of the drug for fatigue alleviation, we conducted using URSA Complex to evaluate the efficacy on physical fatigue via score changes in the checklist individual strength (CIS). Methods: The study was designed as a multicenter, randomized, double-blind, placebo-controlled trial, with subjects randomized to one of the two arms, receiving either placebo or URSA Complex administered as identical capsules. The primary efficacy endpoints of this clinical trials are the ratio of improving CIS scores < 76 points in patients at the end (4 weeks). Secondary efficacy variables are as follows one is an improvement of fatigue and the other is an improvement of the liver enzyme. Results: The fatigue recovery rate in who had improved CIS scores of < 76 points were 70.0%, 50.9% in the therapy group and placebo group, respectively (P = 0.019). The fatigue recovery rate in CIS score was higher in URSA Complex therapy group than placebo group. The difference between therapy group and placebo group was statistically significant at 4 weeks later, but not 2 weeks. Conclusions: Our results provided that the URSA Complex was effective in alleviating physical fatigue. The adverse event frequency in the therapy groups was similar to that in the placebo group. PMID:26830981

  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. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial

    PubMed Central

    Ozawa, Hideki; Uemura, Naomi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the 13C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), 13C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  19. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial.

    PubMed

    Takagi, Atsushi; Yanagi, Hidetaka; Ozawa, Hideki; Uemura, Naomi; Nakajima, Shigemi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the (13)C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), (13)C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  20. 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

  1. 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

  2. Efficacy and safety of two pH-dependent-release mesalamine doses in moderately active ulcerative colitis: a multicenter, randomized, double-blind, parallel-group study

    PubMed Central

    Suzuki, Yasuo; Iida, Mitsuo; Ito, Hiroaki; Saida, Isamu

    2016-01-01

    Background/Aims The therapeutic effect of mesalamine is considered to be dose-dependent; however, no consensus has been reached regarding the optimal doses for individual patients. This study aimed to provide new insight for dose optimization using two doses of pH-dependent release mesalamine for induction of remission of moderately active ulcerative colitis (UC). Methods In a multicenter, double-blind, randomized study, 110 patients with moderately active UC were assigned to two groups after treatment with a constant dose of mesalamine. Fifty-five patients were treated with a pH-dependent release formulation of 3.6 or 4.8 g/day for 8 weeks. The primary endpoint was a decrease in the UC disease activity index (UCDAI) adjusted by covariates. Results In the full analysis set (n=110), the mean decrease in UCDAI was 3.1 in the 3.6 g/day group and 3.4 in the 4.8 g/day group (P>0.05). In a subgroup analysis, the effectiveness of the 4.8 g/day dose was greater in particular populations, such as those who had been previously treated with a lower dose of mesalamine and those with more severe disease. The safety was comparable between the two groups. Conclusions The results suggest that treatment with pH-dependent release mesalamine at either 3.6 or 4.8 g/day was effective and safe for the induction of remission in patients with moderately active UC. However, the patients receiving mesalamine at 2.4 g/day but in whom the therapeutic effect is not sufficient and having more severe symptoms (UCDAI 9-10), benefit from higher doses of mesalamine compared to others. PMID:26884735

  3. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial

    PubMed Central

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

    2015-01-01

    A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8–67.2), 53.4% (95% CI: 48.1–58.7), and 54.9% (95% CI: 48.1–60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6–97.3), 93.8% (95% CI: 91.2–96.4), and 95.3% (95% CI: 93.0–97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective. PMID:25875868

  4. Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double-blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder.

    PubMed

    Benkert, Otto; Szegedi, Armin; Philipp, Michael; Kohnen, Ralf; Heinrich, Claus; Heukels, Anja; van der Vegte-Senden, Monique; Baker, Ross A; Simmons, John H; Schutte, Albert-Jan

    2006-02-01

    This randomized, multicenter, double-blind study was designed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets (ODT) with venlafaxine extended-release (XR) formulation in outpatients with major depression. Both treatments were administered in a rapidly escalating dosing regimen. Target doses (mirtazapine ODT, 45 mg OD; venlafaxine XR, 225 mg OD) were reached by day 6 of treatment. On the primary efficacy parameter [the average of the change in HAM-D (17-item) total score on days 5, 8, 11, and 15], mirtazapine ODT was significantly superior to venlafaxine XR (P = 0.008). In addition, calculating the HAM-D score without the sleep items resulted in significant reductions in favor of mirtazapine ODT on days 8 (P = 0.006) and 11 (P = 0.037). The proportion of responders (HAM-D decrease of > or =50% from baseline) was higher in the mirtazapine ODT group on all assessment days, being significant on days 8 (P = 0.002), 11 (P = 0.004), and 22 (P = 0.027). More patients in the mirtazapine ODT group achieved remission (HAM-D total score of < or =7) up to day 29, and the difference was statistically significant on day 15 (P = 0.016). Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 (P = 0.019), 11 (P = 0.004), and 15 (P = 0.031), and the CGI of severity on days 8 (P = 0.014) and 11 (P = 0.033). Both treatments were well tolerated. These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder, and that this effect is independent of its sleep-improving properties. PMID:16415711

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

    PubMed Central

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

    2015-01-01

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

  6. Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double-Blind, Randomized Controlled Trial

    PubMed Central

    Cao, Yuxue; Du, Yijie; Zhang, Hongying; Luo, Qingli; Li, Bei; Wu, Jinfeng; Lv, Yubao; Sun, Jing; Jin, Hualiang; Wei, Kai; Zhao, Zhengxiao; Kong, Lingwen; Zhou, Xianmei; Miao, Qing; Wang, Gang; Zhou, Qingwei; Dong, Jingcheng

    2014-01-01

    Objective The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. Methods A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. Results A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. Conclusions BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Trial Registration Chinese Clinical Trial Register center ChiCTR-TRC-09000530 PMID:25118962

  7. 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

  8. Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study

    PubMed Central

    Gutierrez, Juan E; Rosenberg, Martin; Seemann, Jörg; Breuer, Josy; Haverstock, Daniel; Agris, Jacob; Balzer, Thomas; Anzalone, Nicoletta

    2015-01-01

    PURPOSE Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood–brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight. MATERIALS AND METHODS Prospective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology. RESULTS Of the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%). CONCLUSION Gadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity. PMID:25922578

  9. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

    PubMed

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

    2015-01-01

    A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective. PMID:25875868

  10. Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial

    PubMed Central

    Jiang, Yan; Zhang, Zhen-Lin; Zhang, Zhong-Lan; Zhu, Han-Min; Wu, Yi-Yong; Cheng, Qun; Wu, Feng-Li; Xing, Xiao-Ping; Liu, Jian-Li; Yu, Wei; Meng, Xun-Wu

    2014-01-01

    Objective To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. Method This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. Results A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. Conclusion Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women. PMID:24426779

  11. Efficacy of frovatriptan versus other triptans in the acute treatment of menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies.

    PubMed

    Allais, Gianni; Tullo, Vincenzo; Omboni, Stefano; Benedetto, Chiara; Sances, Grazia; Zava, Dario; Ferrari, Michel D; Bussone, Gennaro

    2012-05-01

    The objective of this study was to review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), in women with menstrually related migraine (IHS criteria) through a pooled analysis of three individual studies. Subjects with a history of migraine with or without aura were randomized to F 2.5 mg or R 10 mg (study 1), F or Z 2.5 mg (study 2), and F or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double-blind, crossover design. After treating three episodes of migraine in no more than 3 months with the first treatment, patients had to switch to the next treatment for other 3 months. 346 subjects formed intention-to-treat population of the main study; 280 of them were of a female gender, 256 had regular menses and 187 were included in the menstrual migraine subgroup analysis. Rate of pain free at 2, 4 and 24 h was 23, 52 and 67 % with F and 30, 61 and 66 % with comparators (P = NS). Pain relief episodes at 2, 4 and 24 h were 37, 60 and 66 % for F and 43, 55 and 61 % for comparators (P = NS). Rate of recurrence was significantly (P < 0.05) lower under F either at 24 h (11 vs. 24 % comparators) or at 48 h (15 vs. 26 % comparators). Number of menstrual migraine attacks associated with drug-related adverse events was equally low (P = NS) between F (5 %) and comparators (4 %). PMID:22644174

  12. Frovatriptan vs. other triptans for the acute treatment of oral contraceptive-induced menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies.

    PubMed

    Allais, G; Tullo, V; Omboni, S; Pezzola, D; Zava, D; Benedetto, C; Bussone, G

    2013-05-01

    Oral contraceptive-induced menstrual migraine (OCMM) is a particularly severe form of migraine triggered by the cyclic hormone withdrawal. To review the efficacy of frovatriptan vs. other triptans, in the acute treatment of OCMM through a pooled analysis of three individual randomized Italian studies. With or without aura migraineurs were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, the subset of 35 of the 280 women of the intention-to-treat population taking combined oral contraceptives and experiencing a migraine attack during the withdrawal phase, were analyzed. The proportion of pain free and pain relief at 2 h were 25 and 51 % with frovatriptan and 28 and 48 % with comparators (p = NS). At 24 h, 71 and 83 % of frovatriptan-treated patients and 60 and 76 % of comparator-treated patients were pain free (p < 0.05 between treatments) and had pain relief (p = NS), respectively. Relapse at 24 and 48 h was significantly (p < 0.05) lower with frovatriptan (17 and 21 %) than with the comparators (27 and 31 %). Our results suggest that, due to its sustained antimigraine effect, frovatriptan may be particularly suitable for the management of OCMM than other triptans. PMID:23695052

  13. Frovatriptan versus other triptans in the acute treatment of migraine: pooled analysis of three double-blind, randomized, cross-over, multicenter, Italian studies.

    PubMed

    Cortelli, Pietro; Allais, Gianni; Tullo, Vincenzo; Benedetto, Chiara; Zava, Dario; Omboni, Stefano; Bussone, Gennaro

    2011-05-01

    The objective of the study is to systematically review the efficacy and safety of frovatriptan (F) versus rizatriptan (R), zolmitriptan (Z) and almotriptan (A), through a pooled analysis of three individual studies. 414 subjects with a history of migraine with or without aura (IHS criteria) were randomized to F 2.5 mg or R 10 mg (study 1), F 2.5 mg or Z 2.5 mg (study 2), and F 2.5 mg or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double blind, cross-over design, with each of the two treatment periods lasting not more than 3 months. The number of pain free (PF) and pain relief (PR) episodes at 2 h, and the number of sustained pain free (SPF) and recurrent episodes within the 48 h were the efficacy endpoints. 346 patients were included in the intention-to-treat analysis. Rate of PF episodes at 2 h was 30% with F and 34% with comparators (p = NS). PR episodes at 2 h were 55% for F and 59% for comparators (p = NS). SPF episodes at 48 h were also similar between the two groups (22% F vs. 21% comparators). Rate of recurrence was significantly (p < 0.001) lower under F (27 vs. 40% comparators). Drug-related adverse events were significantly (p < 0.05) less under F, particularly cardiovascular symptoms. Our systematic analysis of individual studies suggests that F has a similar immediate efficacy, but a more sustained effect and a better tolerability than R, Z and A. PMID:21533722

  14. Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study.

    PubMed

    Bartolini, Marco; Giamberardino, Maria Adelaide; Lisotto, Carlo; Martelletti, Paolo; Moscato, Davide; Panascia, Biagio; Savi, Lidia; Pini, Luigi Alberto; Sances, Grazia; Santoro, Patrizia; Zanchin, Giorgio; Omboni, Stefano; Ferrari, Michel D; Fierro, Brigida; Brighina, Filippo

    2012-07-01

    The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.5 mg in a randomized sequence: after treating 3 episodes of migraine in no more than 3 months with the first treatment, the patient was switched to the other treatment. 67 of the 96 female patients of the intention-to-treat population of the main study had regular menstrual cycles and were thus included in this subgroup analysis. 77 migraine attacks classified as related to menses were treated with frovatriptan and 78 with almotriptan. Rate of pain relief at 2 and 4 h was 36 and 53 % for frovatriptan and 41 and 50 % for almotriptan (p = NS between treatments). Rate of pain free at 2 and 4 h was 19 and 47 % with frovatriptan and 29 and 54 % for almotriptan (p = NS). At 24 h, 62 % of frovatriptan-treated and 67 % of almotriptan-treated patients had pain relief, while 60 versus 67 % were pain free (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (8 vs. 21 % almotriptan). This was the case also at 48 h (9 vs. 24 %, p < 0.05). Frovatriptan was as effective as almotriptan in the immediate treatment of menstrually related migraine attacks. However, it showed a more favorable sustained effect, as shown by a lower rate of migraine recurrence. PMID:22592864

  15. Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study

    PubMed Central

    Hanling, Steven; Bicket, Mark C; White, Ronald L; Veizi, Elias; Kurihara, Connie; Zhao, Zirong; Hayek, Salim; Guthmiller, Kevin B; Griffith, Scott R; Gordin, Vitaly; White, Mirinda Anderson; Vorobeychik, Yakov; Pasquina, Paul F

    2015-01-01

    Objective To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy. Design A multicenter randomized study conducted between 2011 and 2014. Computer generated randomization was stratified by site. Patients and evaluating physicians were blinded to treatment outcomes. Settings Eight military, Veterans Administration, and civilian hospitals. Participants 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain. Interventions Participants received either epidural steroid injection plus placebo pills or sham injection plus gabapentin. Main outcome measures Average leg pain one and three months after the injection on a 0-10 numerical rating scale. A positive outcome was defined as a ≥2 point decrease in leg pain coupled with a positive global perceived effect. All patients had one month follow-up visits; patients whose condition improved remained blinded for their three month visit. Results There were no significant differences for the primary outcome measure at one month (mean pain score 3.3 (SD 2.6) and mean change from baseline −2.2 (SD 2.4) in epidural steroid injection group versus 3.7 (SD 2.6) and −1.7 (SD 2.6) in gabapentin group; adjusted difference 0.4, 95% confidence interval −0.3 to 1.2; P=0.25) and three months (mean pain score 3.4 (SD 2.7) and mean change from baseline −2.0 (SD 2.6) versus 3.7 (SD 2.8) and −1.6 (SD 2.7), respectively; adjusted difference 0.3, −0.5 to 1.2; P=0.43). Among secondary outcomes, one month after treatment those who received epidural steroid injection had greater reductions in worst leg pain (−3.0, SD 2.8) than those treated with gabapentin (−2.0, SD 2.9; P=0.04) and were more likely to experience a positive successful outcome (66% v 46%; number needed to treat=5.0, 95% confidence interval 2.8 to 27.0; P=0.02). At three

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

    PubMed Central

    2012-01-01

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

  17. The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial

    PubMed Central

    Hua, Wei; Gao, Run-Lin; Zhao, Bu-Chang; Wang, Jing; Chen, Xu-Hua; Cai, Chi; Zhang, Shu

    2015-01-01

    Background: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. Methods: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. Results: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%, P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%, P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. Conclusions: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC

  18. Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial

    PubMed Central

    Rauš, Karel; Pleschka, Stephan; Klein, Peter; Schoop, Roland; Fisher, Peter

    2015-01-01

    Background Echinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu. Objectives This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza. Methods Following informed consent, 473 patients with early influenza symptoms (≤48 hours) were recruited in primary care in the Czech Republic and randomized to either 5 days of oseltamivir followed by 5 days of placebo, or 10 days of an Echinacea purpurea-based formulation called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil, Switzerland). The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for noninferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (2-sided) and using a CI approach in the per-protocol sample. Results Recovery from illness was comparable in the 2 treatment groups at 1.5% versus 4.1% after 1 day, 50.2% versus 48.8% after 5 days, and 90.1% versus 84.8% after 10 days of treatment with Echinaforce Hotdrink and oseltamivir, respectively. Noninferiority was demonstrated for each day and overall (95% CI, 0.487–0.5265 by generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce Hotdrink than with oseltamivir (2.46% vs 6.45%; P = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink. Conclusions Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive

  19. Treatment of major depressive disorders with generic duloxetine and paroxetine: a multi-centered, double-blind, double-dummy, randomized controlled clinical trial

    PubMed Central

    WANG, Zhiyang; XU, Xiufeng; TAN, Qingrong; LI, Keqing; MA, Cui; XIE, Shiping; GAO, Chengge; WANG, Gang; LI, Huafang

    2015-01-01

    Background This study is a pre-registration trial of generic duloxetine that was approved by the China Food and Drug Administration (approval number: 2006L01603). Aims Compare the treatment efficacy and safety of generic duloxetine to that of paroxetine in patients with major depressive disorders (MDD). Methods This was a double-dummy, double-blind, multicenter, positive drug (paroxetine), parallel randomized controlled clinical trial. The 299 patients with MDD recruited for the study were randomly assigned to use duloxetine (n=149; 40–60 mg/d) or paroxetine (n=150; 20 mg/d) for 8 weeks. The Hamilton Depression rating scale (HAMD-17) was administered at baseline and 1, 2, 4, 6, and 8 weeks after starting treatment. Remission was defined as a HAMD-17 score below 8 at the end of the trial, and treatment effectiveness was defined as a decrease in baseline HAMD-17 score of at least 50% by the end of the trial. Safety was assessed based on the reported prevalence and severity of side effects and changes in laboratory and electrocardiographic findings. Three patients in the duloxetine group dropped out before starting medication, so results were analyzed using a modified intention-to-treat (ITT) method with 146 in the experimental group and 150 in the control group. Results Both groups experienced 29 dropouts during the 8-week trial. HAMD-17 scores decreased significantly from baseline throughout the trial in both groups. Based on the ITT analysis, at the end of the trial there was no significant difference between the duloxetine group and the paroxetine group in effectiveness (67.1% v. 71.3%, X2=0.62 p=0.433), remission rate (41.1% v. 51.3%, X2=3.12, p=0.077), or in the incidence of side effects (56.8% v. 54.7%, X2=0.14, p=0.705). Conclusions Generic duloxetine is as effective and safe as paroxetine in the acute treatment of patients with MDD who seek care at psychiatric outpatient departments in China. PMID:26549959

  20. 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

  1. 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

  2. A prospective, randomized, double-blind, and multicenter trial of prophylactic effects of ramosetronon postoperative nausea and vomiting (PONV) after craniotomy: comparison with ondansetron

    PubMed Central

    2014-01-01

    Background Craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). This prospective, randomized, double-blind, multi-center study was performed to evaluate the efficacy of prophylactic ramosetron in preventing PONV compared with ondansetron after elective craniotomy in adult patients. Methods A total of 160 American Society of Anesthesiologists physical status I–II patients aged 19–65 years who were scheduled to undergo elective craniotomy for various intracranial lesions were enrolled in this study. All patients received total intravenous anesthesia (TIVA) with propofol and remifentanil. Patients were randomly allocated into three groups to receive ondansetron (4 mg; group A, n  =  55), ondansetron (8 mg; group B, n  =  54), or ramosetron (0.3 mg; group C, n  =  51) intravenously at the time of dural closure. The incidence of PONV, the need for rescue antiemetics, pain score, patient-controlled analgesia (PCA) consumption, and adverse events were recorded 48 h postoperatively. Results Among the initial 160 patients, 127 completed the study and were included in the final analysis. The incidences of PONV were lower (nausea, 14% vs. 59% and 41%, respectively; P  <  0.001; vomiting, P  =  0.048) and the incidence of complete response was higher (83% vs. 37% and 59%, respectively; P  <  0.001) in group C than in groups A and B at 48 h postoperatively. There were no significant differences in the incidence of PONV or need for rescue antiemetics 0–2 h postoperatively, but significant differences were observed in the incidence of PONV and complete response among the three groups 2–48 h postoperatively. No statistically significant intergroup differences were observed in postoperative pain, PCA consumption, or adverse events. Conclusion Intravenous administration of ramosetron at 0.3 mg reduced the incidence of PONV and rescue antiemetic requirement in craniotomy patients

  3. 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

  4. A Randomized, Double Blind, Placebo-Controlled, Multicenter Phase II Trial of Allisartan Isoproxil in Essential Hypertensive Population at Low-Medium Risk

    PubMed Central

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

    2015-01-01

    Background Angiotensin II receptor blockers (ARBs) is a well-tolerated class of antihypertensive agents, exhibiting effective antihypertensive and cardiovascular protective function. The objective of the study was to examine the efficacy and safety of Allisartan Isoproxil, a newly developed, selective, nonpeptide blocker of the angiotensin II type 1 receptor (AT1R), in essential hypertensive patients at low-medium risk. Methods and Findings A Phase II prospective, randomized, double-blind, placebo-controlled, multicenter trial comparing Allisartan Isoproxil 240mg versus placebo was conducted in essential hypertensive patients at low-medium risk at 8 sites in China. After a 2-week placebo baseline period, 275 patients received once-daily treatment with Allisartan Isoproxil 240mg or placebo randomly for 8 weeks. Systolic/diastolic blood pressure (SBP/DBP) was measured at week 2, 4 and 8. By the end of treatment, mean reductions from baseline of SBP and DBP in Allisartan Isoproxil and placebo groups were 14.5/10.4 and 8.3/7.7 mmHg, respectively (P<0.01). The rate of effective blood pressure control in Allisartan Isoproxil group was significantly higher than in placebo group at week 4 (61.3% vs 50.0%, P<0.05) and week 8 (67.2% vs 48.6%, P<0.01). In terms of safety and tolerability, there were no report of death and serious adverse event (SAE) in all subjects. There was no difference of frequency between two groups in adverse event (AE) and adverse drug reaction (ADR) (P>0.05). No one withdraw because of an ADR in two groups. 124 patients received additional 56 weeks treatment with Allisartan Isoproxil and 84 of them completed the study. The rate of effective BP control kept up to 80% since week 24. No significant clinical change was observed and ADRs were generally mild or moderate during the long-term study. Conclusions/Significance Allisartan Isoproxil 240mg was effective and safe for essential hypertension patients at low-medium risk. Trial Registration http

  5. Effectiveness and safety of generic memantine hydrochloride manufactured in China in the treatment of moderate to severe Alzheimer's disease: a multicenter, double-blind randomized controlled trial

    PubMed Central

    Zhu, Minjie; Xiao, Shifu; Li, Guanjun; Li, Xia; Tang, Mouni; Yang, Siming; Xu, Xiufeng; Feng, Lianyuan; Liu, Kaixiang; Hu, Lianping

    2013-01-01

    Background Memantine hydrochloride is a N-methyl-D-aspartate (NMDA) antagonist that may be useful in the treatment of Alzheimer's disease. Aim Compare the efficacy and safety of generic memantine hydrochloride produced in China to that of the imported proprietary version of the medication (Ebixa) in the treatment of moderate to severe Alzheimer's disease (AD). Methods In this multicenter, double-blind randomized controlled trial 229 patients with moderate to severe AD were randomly assigned to a 16-week trial of either the generic preparation or the proprietary preparation of memantine hydrochloride. All participants were assessed at baseline and at 4, 8, 12 and 16 weeks after enrolment. The primary outcome variable was the Alzheimer Disease Assessment Scale-cognition (ADAS-Cog) score. Secondary outcomes were scores in the Mini-Mental State Examination (MMSE), the Activities of Daily Living (ADL) scale and the Clinical Global Impression (CGI) scale. Results Sample sizes for the safety set (SS) analysis, full analysis set (FAS) and per protocol set (PPS) analysis were 112, 109 and 103 in the generic medication group, and 111, 107 and 101 in the proprietary medication group, respectively. The ADAS-Cog and ADL total scores at the end of weeks 4, 8, 12, and 16 decreased significantly compared with baseline for both groups (p<0.001) and the MMSE total scores at the end of weeks 4, 8, 12, and 16 increased significantly compared with baseline for both groups (p<0.001). There were no significant differences in ADAS-Cog total scores, ADL total scores and level of improvement based on the CGI scores between the two groups at any of the follow-up assessments. The occurrence of adverse events was 20.5% in the generic medication group and 27.0% in the proprietary medication group; this difference was not statistically significant (χ2=1.30, p=0.255). Conclusion There are no significant differences in the effectiveness or safety between memantine that is generically produced in

  6. Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs. other triptans.

    PubMed

    Franconi, Flavia; Finocchi, Cinzia; Allais, Gianni; Omboni, Stefano; Tullo, Vincenzo; Campesi, Ilaria; Reggiardo, Giorgio; Benedetto, Chiara; Bussone, Gennaro

    2014-05-01

    Migraine is three times as common in females as in males, and attacks may be more severe and difficult to treat in women. However, no study specifically addressed possible gender differences in response to antimigraine therapy. The objective of this study was to review the efficacy of frovatriptan vs. other triptans, in the acute treatment of migraine in subgroups of subjects classified according to gender (men vs. women) through a pooled analysis of three individual randomized Italian studies. 414 patients suffering from migraine with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in no more than 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, traditional migraine endpoints were compared between the 66 men and 280 women of the intent-to-treat population. At baseline, long-term and debilitating migraine attacks were more frequently reported by women than men. During the observation period, the proportion of pain-free attacks at 2 h did not significantly differ between frovatriptan and the comparators in either men (32 vs. 38 %, p = NS) or women (30 vs. 33 %, p = NS). Pain relief was also similar between treatments for both genders (men: 56 % frovatriptan vs. 57 % comparators; women: 55 vs. 57 %; p = NS for both). The rate of relapse was significantly lower with frovatriptan than with the comparators in men (24 h: 10 vs. 30 %; 48 h: 21 vs. 39 %; p < 0.05) as well as in women (24 h: 14 vs. 23 %; 48 h: 28 vs. 40 %; p < 0.05). The rate of adverse drug reactions was significantly larger with comparators, irrespectively of gender. Although migraine presents in a more severe form in women, frovatriptan seems to retain its good efficacy and

  7. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial

    PubMed Central

    HASSAN, S. S.; ROMERO, R.; VIDYADHARI, D.; FUSEY, S.; BAXTER, J. K.; KHANDELWAL, M.; VIJAYARAGHAVAN, J.; TRIVEDI, Y.; SOMA-PILLAY, P.; SAMBAREY, P.; DAYAL, A.; POTAPOV, V.; O’BRIEN, J.; ASTAKHOV, V.; YUZKO, O.; KINZLER, W.; DATTEL, B.; SEHDEV, H.; MAZHEIKA, L.; MANCHULENKO, D.; GERVASI, M. T.; SULLIVAN, L.; CONDE-AGUDELO, A.; PHILLIPS, J. A.; CREASY, G. W.

    2012-01-01

    Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the ef cacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10–20 mm) at 19 + 0to23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred rst. Randomization sequence was strati ed by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33–0.92; P = 0.02). The effect remained signi cant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31–0.91; P = 0.02). Vaginal progesterone was also associated with a signi cant reduction in the rate of preterm birth before 28 weeks(5.1%vs10.3%; RR, 0.50;95%CI, 0.25–0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42–0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17–0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33–0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26–0.85; P = 0.01). There were no differences

  8. A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial

    PubMed Central

    Cusato, Maria; Ingelmo, Pablo; Niebel, Thekla Larissa; Somaini, Marta; Riva, Francesca; Tinelli, Carmine; De Andrés, José; Fanelli, Guido; Braschi, Antonio; Regazzi, Mario; Allegri, Massimo

    2015-01-01

    BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 μg/mL or of ropivacaine 0.2% + sufentanil 0.75 μg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion

  9. A double-blind, multicenter, parallel-group trial with 0.05% halobetasol propionate ointment versus 0.1% diflucortolone valerate ointment in patients with severe, chronic atopic dermatitis or lichen simplex chronicus.

    PubMed

    Brunner, N; Yawalkar, S

    1991-12-01

    In a double-blind, parallel-group, multicenter, comparative trial in 120 evaluable patients with chronic, localized atopic dermatitis or lichen simplex chronicus, the success rate (described as "healed" and "marked improvement") was 91.5% in patients treated with halobetasol propionate ointment and 83.6% in those in the diflucortolone valerate treatment group. Of patients treated with halobetasol propionate ointment, 40.7% reported healing within 17 days, whereas of those in the diflucortolone valerate treatment group, 32.8% reported healing within that time. Early onset of therapeutic effect, that is, within 3 days of the start of treatment, was reported in a higher percentage of patients treated with halobetasol propionate ointment than in those treated with diflucortolone valerate ointment (70% versus 59%). Adverse effects at the site of application were less frequently reported in patients belonging to the halobetasol propionate treatment group than in those treated with diflucortolone valerate ointment (3% versus 8%). PMID:1757609

  10. A Randomized, Double-blind, Placebo-controlled, Multi-center, Extension Trial Evaluating the Efficacy of a New Oral Supplement in Women with Self-perceived Thinning Hair

    PubMed Central

    Dayan, Steven

    2015-01-01

    Objective: The purpose of this six-month, randomized, double-blind, multi-center, placebo-controlled study was to determine if the administration of a new oral supplement will promote terminal hair growth. Design: A randomized, double-blind study. Setting: Two private practices (dermatology and facial plastics). Participants: Women 21 to 75 years of age with self-perceived thinning hair. Measurements: The primary efficacy endpoint was the change in terminal and vellus hairs in a 4cm2 target area of the scalp after 90 and 180 days of treatment. Secondary endpoints were change in hair diameter and responses to Quality of Life and Self-Assessment questionnaires. Results: Subjects treated with the new oral supplement achieved a significant increase in the number of baseline terminal hairs at 90 and 180 days (for each, p<0.0001, respectively) and were significantly greater then placebo (p<0.0001). Treatment with the new oral supplement was also associated with a significant increase in baseline terminal hair diameter after 90 (p=0.006) and 180 days of treatment (p=0.001) which was significantly greater than placebo at the end of the study (p=0.003). Improvements in hair growth and hair diameter were associated with significant improvement in most responses to Self-Assessment and Quality of Life Questionnaire responses. There were no adverse events. Conclusion: The daily administration of a new oral supplement was associated with significant increases in the number of terminal and vellus hairs and hair diameter. Most study participants believed the use of the oral supplement resulted in significant improvement in skin and hair quality and quality of life. PMID:26705444

  11. 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

  12. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression.

    PubMed

    Reimherr, F W; Chouinard, G; Cohn, C K; Cole, J O; Itil, T M; LaPierre, Y D; Masco, H L; Mendels, J

    1990-12-01

    A double-blind, placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline, a specific serotonin uptake inhibitor. Patients with DSM-III-defined major depression randomly received either sertraline (N = 149), amitriptyline (N = 149), or placebo (N = 150) once daily for the 8-week study period. The mean final daily medication dose for the all-patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups, respectively. As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale, both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline (p less than or equal to .001) than the placebo group. The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group. The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo. PMID:2258378

  13. Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: a multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial.

    PubMed

    Habib, G B; Dunbar, L M; Rodrigues, R; Neale, A C; Friday, K J

    1995-05-01

    This study was a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of oral nicardipine for the treatment of urgent hypertension in the emergency department. Of 57 patients with urgent hypertension 53 patients were enrolled: 36 men and 17 women, 43 black and 10 white, age range 48 +/- 11 years, and diastolic blood pressure 128 +/- 7 mm Hg. Patients were randomly assigned to receive 30 mg nicardipine or placebo in blind fashion followed by 30 mg open-label nicardipine in nonresponders. Responders to one or two doses of nicardipine received 30 or 40 mg nicardipine three times a day for 1 week after discharge from the emergency department. Adequate blood pressure reduction, defined as a reduction of diastolic blood pressure to less than 100 mm Hg or by at least 20 mm Hg, was achieved in 65% and 22% of patients who received 30 mg nicardipine or placebo (p = 0.002). Adequate blood pressure reduction after administration of open-label nicardipine occurred in 76% of the nonresponders to placebo. Blood pressure reductions were maintained at 1 week after discharge. The drug was well tolerated, and no significant adverse events occurred. We conclude that oral nicardipine is a safe and effective drug for the initial treatment of urgent hypertension. PMID:7732981

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

    PubMed Central

    2014-01-01

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

  15. Efficacy of DA-9701 (Motilitone) in Functional Dyspepsia Compared to Pantoprazole: A Multicenter, Randomized, Double-blind, Non-inferiority Study

    PubMed Central

    Jung, Hye-Kyung; Lee, Kwang Jae; Choi, Myung-Gyu; Park, Hyojin; Lee, Joon Seong; Rhee, Poong-Lyul; Kim, Nayoung; Park, Kyung Sik; Choi, Suck Chei; Lee, Oh Young; Huh, Kyu Chan; Song, Geun Am; Hong, Su Jin; Sohn, Chong Il; Jung, Hwoon-Yong; Lee, Yong Chan; Rew, Jong Sun; Jee, Sam Ryong; Kwon, Joong Goo

    2016-01-01

    Background/Aims The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Western countries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. Methods In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among 3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. The primary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. Results The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptom improvement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups. Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes and dyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. Conclusions DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacy of DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 and pantoprazole in patients with FD. PMID:26811504

  16. A multicenter, double-blind study to evaluate the efficacy and safety of 2 treatments in participants with mild to moderate acne vulgaris.

    PubMed

    Draelos, Zoe Diana; Shalita, Alan R; Thiboutot, Diane; Oresajo, Christian; Yatskayer, Margarita; Raab, Susanna

    2012-06-01

    Acne treatment regimens have changed due to the recent over-the-counter (OTC) switch of all prescription benzoyl peroxide (BPO) topical preparations. The elimination of prescription single-agent BPO products means that dermatologists must select from a variety of OTC formulations to utilize the time-tested efficacy of BPO in the treatment of mild to moderate acne. Our research compared the efficacy and safety of an OTC BPO 5.5% formulation with lipohydroxy acid and tretinoin cream 0.025% with prescription clindamycin 1%-BPO 5% gel and tretinoin cream 0.025%. Parity was demonstrated between the 2 treatment regimens at 12 weeks. PMID:22838094

  17. Efficacy and Safety of Tangshen Formula on Patients with Type 2 Diabetic Kidney Disease: A Multicenter Double-Blinded Randomized Placebo-Controlled Trial

    PubMed Central

    Li, Ping; Chen, Yiping; Liu, Jianping; Hong, Jing; Deng, Yueyi; Yang, Fang; Jin, Xiuping; Gao, Jing; Li, Jing; Fang, Hui; Liu, Geling; Shi, Liping; Du, Jinhang; Li, Yang; Yan, Meihua; Wen, Yumin; Yang, Wenying

    2015-01-01

    Background Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD. Methods The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events. Findings After 24 weeks of treatment, no statistically significant difference in UAER (TSF −19.53 μg/min compared with placebo −7.01 μg/min, with a mean difference of −12.52 μg/min; 95%CI, −68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF−0.21 g compared with placebo 0.36 g, with a mean difference of −0.57g; 95%CI, −1.05 to −0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, −0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events. Conclusions Based on conventional

  18. Efficacy of Grintuss® pediatric syrup in treating cough in children: a randomized, multicenter, double blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Cough is an extremely common problem in pediatrics, mostly triggered and perpetuated by inflammatory processes or mechanical irritation leading to viscous mucous production and increased sensitivity of the cough receptors. Protecting the mucosa might be very useful in limiting the contact with micro-organisms and irritants thus decreasing the inflammation and mucus production. Natural molecular complexes can act as a mechanical barrier limiting cough stimuli with a non pharmacological approach but with an indirect anti-inflammatory action. Objective Aim of the study was to assess the efficacy of a medical device containing natural functional components in the treatment of cough persisting more than 7 days. Methods In this randomized, parallel groups, double-blind vs. placebo study, children with cough persisting more than 7 days were enrolled. The clinical efficacy of the study product was assessed evaluating changes in day- and night-time cough scores after 4 and 8 days (t4 and t8) of product administration. Results In the inter-group analysis, in the study product group compared with the placebo group, a significant difference (t4 study treatment vs. t4 placebo, p = 0.03) was observed at t4 in night-time cough score. Considering the intra-group analysis, only the study product group registered a significant improvement from t0 to t4 in both day-time (t0 vs. t4, p = 0.04) and night-time (t0 vs. t4, p = 0.003) cough scores. A significant difference, considering the study product, was also found in the following intra-group analyses: day-time scores at t4 vs. t8 (p =0.01) and at t0 vs. t8 (p = 0.001); night-time scores at t4 vs. t8 (p = 0.05), and at t0 vs. t8 (p = 0.005). Considering a subgroup of patients with higher cough (≥3) scores, 92.9% of them in the study product group improved at t0 vs. t4 day-time. Conclusions Grintuss® pediatric syrup showed to possess an interesting profile of efficacy and safety in the treatment

  19. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical-controlled, multicenter, double-blind study

    PubMed Central

    Wechsler, Robert T; Li, George; French, Jacqueline; O'Brien, Terence J; D'Cruz, O'Neill; Williams, Paulette; Goodson, Robin; Brock, Melissa

    2014-01-01

    Objective To evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy. Methods This historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16–70 years on stable doses of 1–2 antiepileptic drugs (AEDs) and experiencing 2–40 partial-onset seizures per 28 days during the 8-week prospective Baseline. Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose. Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase. The primary assessment was the Kaplan-Meier–predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%). Results Four hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106). A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases). Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥1 exit criterion; the Kaplan-Meier–predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6–35.5%) was lower than the historical control. When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8–37.8%) was also lower than the historical control. Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%). Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity

  20. 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

  1. 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

  2. Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

    PubMed Central

    2011-01-01

    Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

  3. Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933

    PubMed Central

    Martinez-Torres, Francisco; Menon, Sanjay; Pritsch, Maria; Victor, Norbert; Jenetzky, Ekkehart; Jensen, Katrin; Schielke, Eva; Schmutzhard, Erich; de Gans, Jan; Chung, Chin-Hee; Luntz, Steffen; Hacke, Werner; Meyding-Lamadé, Uta

    2008-01-01

    Background The treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR), aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933 PMID:18959773

  4. 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

  5. The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study

    PubMed Central

    Brams, Matthew; Cutler, Andrew J.; Kollins, Scott H.; Northcutt, Jo; Padilla, Americo; Turnbow, John M.

    2015-01-01

    Abstract Objective: The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Methods: A total of 107 children ages 6–12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs). Results: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%). Conclusions: Compared to placebo, R-AMPH was effective in treating children aged 6–12 years with ADHD

  6. Randomized, Double-Blind, Phase II, Multicenter Study Evaluating the Safety/Tolerability and Efficacy of JNJ-Q2, a Novel Fluoroquinolone, Compared with Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infection ▿ †

    PubMed Central

    Covington, Paul; Davenport, J. Michael; Andrae, David; O'Riordan, William; Liverman, Lisa; McIntyre, Gail; Almenoff, June

    2011-01-01

    JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. Primary intent-to-treat analysis was unable to declare noninferiority, as the risk difference lower bound of the 95% confidence interval between treatments was 19% at 36 to 84 h postrandomization for the composite end point of lesion assessment and temperature. Prespecified clinical cure rates 2 to 14 days after completion of therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hoc analyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4% versus 57.7%, respectively; P = 0.024) based on the 2010 FDA guidance, which defines treatment success as lack of lesion spread and afebrile status within 48 to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients presented with fever, suggesting fever is not a compelling surrogate measure of systemic disease resolution for this indication. Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature. PMID:21947389

  7. Treatment of children with attention-deficit/hyperactivity disorder: results of a randomized, multicenter, double-blind, crossover study of extended-release dexmethylphenidate and D,L-methylphenidate and placebo in a laboratory classroom setting.

    PubMed

    Silva, Raul; Muniz, Rafael; McCague, Kevin; Childress, Ann; Brams, Matthew; Mao, Alice

    2008-01-01

    The purpose of this study was to compare the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) to that of d,l-MPH-ER and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. This multicenter, double-blind, crossover study randomized 82 children, 6 to 12 years of age, stabilized on a total daily dose to the nearest equivalent of 40 to 60 mg of d,l-MPH or 20 or 30 mg/day of d-MPH. Patients participated in a screening day and practice day, and were randomized to 1 of 10 sequences of all five treatments in five separate periods. Treatments included d-MPH-ER (20 mg/day), d-MPH-ER (30 mg/day), d,l-MPH-ER (36 mg/day), d,l-MPH-ER (54 mg/day), and placebo. Primary efficacy was measured by the change from predose on the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2-h postdose during the 12-h laboratory assessment (d-MPH-ER 20 mg/day vs. d,l-MPH-ER 36 mg/day). Adverse events were monitored throughout the study period. d-MPH-ER (20 mg/day) was significantly more effective than d,l-MPH-ER (36 mg/day) in the primary efficacy variable, change from predose to 2-h postdose in SKAMP-combined score. In general, d-MPH-ER had an earlier onset of action than d,l-MPH-ER, while d,l-MPH-ER had a stronger effect at 12-h postdose. No serious adverse events were reported. Treatment with either agent was associated with significant improvements in ADHD symptoms. d-MPH-ER and d,l-MPH-ER can be differentiated on what part of the day each is more effective. PMID:18362868

  8. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge

    PubMed Central

    Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

    2016-01-01

    Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

  9. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.

    PubMed

    Elli, Luca; Tomba, Carolina; Branchi, Federica; Roncoroni, Leda; Lombardo, Vincenza; Bardella, Maria Teresa; Ferretti, Francesca; Conte, Dario; Valiante, Flavio; Fini, Lucia; Forti, Edoardo; Cannizzaro, Renato; Maiero, Stefania; Londoni, Claudio; Lauri, Adriano; Fornaciari, Giovanni; Lenoci, Nicoletta; Spagnuolo, Rocco; Basilisco, Guido; Somalvico, Francesco; Borgatta, Bruno; Leandro, Gioacchino; Segato, Sergio; Barisani, Donatella; Morreale, Gaetano; Buscarini, Elisabetta

    2016-02-01

    Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID:26867199

  10. A Randomized Double-Blind, Double-Dummy, Multicenter Trial of Azasetron versus Ondansetron to Evaluate Efficacy and Safety in the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy

    PubMed Central

    Lee, Hee Yeon; Lee, Kyung Hee; Kim, Bong-Seog; Song, Hong Suk; Yang, Sung Hyun; Kim, Joon Hee; Kim, Yeul Hong; Kim, Jong Gwang; Kim, Sang-We; Kim, Dong-Wan; Kim, Si-Young; Park, Hee Sook

    2014-01-01

    Purpose This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting. Materials and Methods This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6. Results Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events. Conclusion In the present study, azasetron showed inferiority in the control of delayed chemotherapy-induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups. PMID:24520219

  11. Comparative trial of a novel botulinum neurotoxin type A versus onabotulinumtoxinA in the treatment of glabellar lines: a multicenter, randomized, double-blind, active-controlled study.

    PubMed

    Won, Chong Hyun; Kim, Hyun Kyu; Kim, Beom Joon; Kang, Hoon; Hong, Joon Pio; Lee, Su-Young; Kim, Chung-Sei

    2015-02-01

    A novel botulinum neurotoxin type A (DWP450; Daewoong Pharmaceutical, Seoul, Korea) has recently been introduced for the treatment of facial wrinkles. The efficacy of this agent has previously been demonstrated in an in vivo study using an electrophysiological protocol in a rat model. To compare the efficacy and safety of DWP450 with onabotulinumtoxinA (OBoNT) for use in the treatment of glabellar lines, we performed a multicenter, double-blind, randomized, active-controlled trial comparing DWP450 and OBoNT (Allergan Inc., Irvine, CA, USA). A total of 268 subjects with moderate to severe glabellar lines were randomized at a 1:1 ratio. Each patient received treatment with 20 U of study medication. Maximum frown responder rates at week 4 were measured to analyze the primary efficacy endpoint. To evaluate secondary efficacy endpoints, response rates were measured at weeks 8, 12, and 16, at maximum frown and rest. Specifically, responder rates at both maximum frown and at rest were assessed based on clinical photography. Subject degree of satisfaction and self-assessed rate of response were also measured. Adverse events (AEs) were documented to evaluate safety. Responder rate by physician-rating severity at maximal contraction at week 4 was 93.89% in the DWP450 group and 88.64% in OBoNT group. As the lower limit of the 97.5% one-sided confidence interval (-1.53%) surpassed the -15% threshold, we determined that DWP450 was not inferior to OBoNT. For the secondary efficacy endpoint analyses, no significant differences were observed between the two groups for any variable at any point in time. The incidences of AEs were similar for the two groups. Most of AEs were considered mild. DWP450 and OBoNT were comparable in efficacy and safety in the treatment of glabellar lines. PMID:25311357

  12. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

    PubMed

    Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

    2016-06-01

    A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). PMID:26696251

  13. The PanAM study: a multi-center, double-blinded, randomized, non-inferiority study of paracetamol versus non-steroidal anti-inflammatory drugs in treating acute musculoskeletal trauma

    PubMed Central

    2013-01-01

    Background Acute musculoskeletal trauma, including strains, sprains or contusions, occur frequently. Pain management is a crucial component of treatment. However, there is no convincing evidence which drug is superior in managing pain in these patients. The aim of the PanAM Study is to compare analgesic efficacy of three strategies of pain management: paracetamol, diclofenac, or a combination of both in patients with acute musculoskeletal trauma. Methods/design The PanAM Study is a multi-center, double blind randomized controlled trial with non-inferiority design. Included are adult patients presenting to an academic, urban Emergency Department or to a General Practice with acute, blunt, traumatic limb injury. In total, 547 patients will be included using a predefined list of exclusion criteria, to be allocated by randomization to treatment with paracetamol + placebo diclofenac, diclofenac + placebo paracetamol or paracetamol + diclofenac. The hypothesis is that paracetamol will not be inferior to treatment with diclofenac, or the combination of both. Primary outcome will be between-group differences in decrease in pain, measured with Numerical Rating Scales at baseline and at 90 minutes after study drug administration. Secondary outcomes are Numerical Rating Scales at 30 and 60 minutes and measured frequently during three consecutive days after discharge; occurrence of adverse effects; patient satisfaction and an analysis of quality of life and cost-effectiveness. Recruitment started July 2013 and is expected to last a year. Discussion With this multi-center randomized clinical trial we will investigate whether treatment with paracetamol alone is not inferior to diclofenac alone or a combination of both drugs in adult patients with acute musculoskeletal trauma. The main relevance of the trial is to demonstrate the benefits and risks of three commonly used treatment regimens for musculoskeletal trauma. Data that lead to the prevention of severe Non

  14. The bacterial lysate Lantigen B reduces the number of acute episodes in patients with recurrent infections of the respiratory tract: the results of a double blind, placebo controlled, multicenter clinical trial.

    PubMed

    Braido, Fulvio; Melioli, Giovanni; Candoli, Piero; Cavalot, Andrea; Di Gioacchino, Mario; Ferrero, Vittorio; Incorvaia, Cristoforo; Mereu, Carlo; Ridolo, Erminia; Rolla, Giovanni; Rossi, Oliviero; Savi, Eleonora; Tubino, Libero; Reggiardo, Giorgio; Baiardini, Ilaria; di Marco, Eddi; Rinaldi, Gilberto; Canonica, Giorgio Walter; Accorsi, Carlo; Bossilino, Claudia; Bonzano, Laura; DiLizia, Michela; Fedrighini, Barbara; Garelli, Valentina; Gerace, Vincenzo; Maniscalco, Sara; Massaro, Ilaria; Messi, Alessandro; Milanese, Manlio; Peveri, Silvia; Penno, Arminio; Pizzimenti, Stefano; Pozzo, Tiziana; Raie, Alberto; Regina, Sergio; Sclifò, Francesca

    2014-12-01

    Studies in the 1970s and 1980s reported that bacterial lysates (BL) had a prophylactic effect on recurrent respiratory tract infections (RRTI). However, controlled clinical study procedures have evolved substantially since then. We performed a trial using updated methods to evaluate the efficacy of Lantigen B®, a chemical BL. This double blind, placebo controlled, multi-center clinical trial had the primary objective of assessing the capacity of Lantigen B to significantly reduce the total number of infectious episodes in patients with RRTI. Secondary aims were the RRTI duration, the frequency and the severity of the acute episodes, the use of drugs and the number of missed workdays. In the subgroup of allergic patients with RRTI, the number of allergic episodes (AE) and the use of anti-allergic drugs were also evaluated. One hundred and sixty patients, 79 allocated to the treated group (TG) and 81 to the placebo group (PG), were enrolled; 30 were lost during the study and 120 (79 females and 38 males) were evaluated. The PG had 1.43 episodes in the 8-months of follow-up while the TG had 0.86 episodes (p=0.036). A similar result was observed in the allergic patients (1.80 and 0.86 episodes for the PG and the TG, respectively, p=0.047). The use of antibiotics was reduced (mean 1.24 and 2.83 days of treatment for the TG and the PG). Logistic regression analysis indicated that the estimated risk of needing antibiotics and NSAIDs was reduced by 52.1 and 30.6%, respectively. With regard to the number of AE, no significant difference was observed between the two groups, but bronchodilators, antihistamines and local corticosteroids were reduced by 25.7%, 56.2% and 41.6%, respectively, in the TG. Lantigen B significantly reduced the number of infectious episodes in patients with RRTI. This finding suggests a first line use of this drug for the prophylaxis of infectious episodes in these patients. PMID:25445613

  15. The SNAP trial: a double blind multi-center randomized controlled trial of a silicon nitride versus a PEEK cage in transforaminal lumbar interbody fusion in patients with symptomatic degenerative lumbar disc disorders: study protocol

    PubMed Central

    2014-01-01

    Background Polyetheretherketone (PEEK) cages have been widely used in the treatment of lumbar degenerative disc disorders, and show good clinical results. Still, complications such as subsidence and migration of the cage are frequently seen. A lack of osteointegration and fibrous tissues surrounding PEEK cages are held responsible. Ceramic implants made of silicon nitride show better biocompatible and osteoconductive qualities, and therefore are expected to lower complication rates and allow for better fusion. Purpose of this study is to show that fusion with the silicon nitride cage produces non-inferior results in outcome of the Roland Morris Disability Questionnaire at all follow-up time points as compared to the same procedure with PEEK cages. Methods/Design This study is designed as a double blind multi-center randomized controlled trial with repeated measures analysis. 100 patients (18–75 years) presenting with symptomatic lumbar degenerative disorders unresponsive to at least 6 months of conservative treatment are included. Patients will be randomly assigned to a PEEK cage or a silicon nitride cage, and will undergo a transforaminal lumbar interbody fusion with pedicle screw fixation. Primary outcome measure is the functional improvement measured by the Roland Morris Disability Questionnaire. Secondary outcome parameters are the VAS leg, VAS back, SF-36, Likert scale, neurological outcome and radiographic assessment of fusion. After 1 year the fusion rate will be measured by radiograms and CT. Follow-up will be continued for 2 years. Patients and clinical observers who will perform the follow-up visits will be blinded for type of cage used during follow-up. Analyses of radiograms and CT will be performed independently by two experienced radiologists. Discussion In this study a PEEK cage will be compared with a silicon nitride cage in the treatment of symptomatic degenerative lumbar disc disorders. To our knowledge, this is the first randomized controlled

  16. Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

    PubMed

    Wang, Guogan; Wang, Pengbo; Li, Yishi; Liu, Wenxian; Bai, Shugong; Zhen, Yang; Li, Dongye; Yang, Ping; Chen, Yu; Hong, Lang; Sun, Jianhui; Chen, Junzhu; Wang, Xian; Zhu, Jihong; Hu, Dayi; Li, Huimin; Wu, Tongguo; Huang, Jie; Tan, Huiqiong; Zhang, Jian; Liao, Zhongkai; Yu, Litian; Mao, Yi; Ye, Shaodong; Feng, Lei; Hua, Yihong; Ni, Xinhai; Zhang, Yuhui; Wang, Yang; Li, Wei; Luan, Xiaojun; Sun, Xiaolu; Wang, Sijia

    2016-03-01

    The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF).This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ± 5.95 vs -1.82 ± 4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99).1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.). PMID:26945407

  17. Effect of Sitagliptin and Metformin on Prediabetes Progression to Type 2 Diabetes - A Randomized, Double-Blind, Double-Arm, Multicenter Clinical Trial: Protocol for the Sitagliptin and Metformin in PreDiabetes (SiMePreD) Study

    PubMed Central

    2016-01-01

    Background The high prevalence and incidence of type 2 diabetes mellitus (DM), and its associated morbidity and mortality, has prompted growing international interest and effort in the primary prevention of this disease. Primary prevention is possible since type 2 DM is preceded by prediabetes, offering a window opportunity to treat patients, and prevent the emergence of advanced disease. Sitagliptin is an oral dipeptidyl peptidase-IV inhibitor that preserves existing beta cell function and increases beta cell mass. These two effects have been demonstrated both in vitro and in animal studies, and current clinical data show that sitagliptin is safe. Metformin, a biguanide, reduces insulin resistance and inhibits hepatic gluconeogenesis, and has an excellent safety profile. The combination of metformin and sitagliptin, targeting both characteristics of prediabetes (insulin resistance and progressive beta cell degeneration), may potentially slow or halt the progression from prediabetes to type 2 DM. This paper describes the rationale and design of the Sitagliptin and Metformin in PreDiabetes (SiMePreD) study. Objective The aim of this study is to determine the effect of sitagliptin and metformin on progression from prediabetes to type 2 DM. The objectives of the study are to determine the effects of metformin and placebo on glycemic endpoints, the effects of sitagliptin and metformin on glycemic endpoints, the effects of metformin and placebo on incidence of cardiovascular disease and death, and the effects of sitagliptin and metformin on incidence of cardiovascular disease and death. Methods This is a randomized, double-blind, multicenter clinical study that will determine if the combination of metformin and sitagliptin is effective in preventing the progression from prediabetes to type 2 DM. The study will contain two arms (metformin/sitagliptin and metformin/placebo). Primary endpoints include the number of subjects progressing from prediabetes to type 2 DM, the

  18. Efficacy and tolerability of adding coenzyme A 400 U/d capsule to stable statin therapy for the treatment of patients with mixed dyslipidemia: an 8-week, multicenter, double-Blind, randomized, placebo-controlled study

    PubMed Central

    2014-01-01

    Background Patients with mixed hyperlipidemia usually are in need of combination therapy to achieve low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) target values for reduction of cardiovascular risk. This study investigated the efficacy and safety of adding a new hypolipidemic agent, coenzyme A (CoA) to stable statin therapy in patients with mixed hyperlipidemia. Methods In this multi-center, 8-week, double-blind study, adults who had received ≥8 weeks of stable statin therapy and had hypertriglyceridemia (TG level at 2.3-6.5 mmol/L) were randomized to receive CoA 400 U/d or placebo plus stable dosage of statin. Efficacy was assessed by the changes in the levels and patterns of lipoproteins. Tolerability was assessed by the incidence and severity of adverse events (AEs). Results A total of 304 patients with mixed hyperlipidemia were randomized to receive CoA 400 U/d plus statin or placebo plus statin (n = 152, each group). After treatment for 8 weeks, the mean percent change in TG was significantly greater with CoA plus statin compared with placebo plus statin (-25.9% vs -4.9%, respectively; p = 0.0003). CoA plus statin was associated with significant reductions in TC (-9.1% vs -3.1%; p = 0.0033), LDL-C (-9.9% vs 0.1%; p = 0.003), and non- high-density lipoprotein cholesterol (-13.5% vs -5.7%; p = 0.0039). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related. Conclusions In these adult patients with persistent hypertriglyceridemia, CoA plus statin therapy improved TG and other lipoprotein parameters to a greater extent than statin alone and has no obviously adverse effect. Trial registration Current Controlled Trials ClinicalTrials.gov ID NCT01928342. PMID:24382338

  19. Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.

    PubMed

    Poeze, M; Froon, A H; Ramsay, G; Buurman, W A; Greve, J W

    2000-10-01

    Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant

  20. Xuan Bai Cheng Qi formula as an adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs: a multicenter, randomized, double-blind, placebo-controlled clinical trial

    PubMed Central

    2014-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality. Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy. This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs. Methods A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 244 patients were divided into the intervention group (n = 122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n = 122, treated with conventional medicine and placebo). Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded. Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment. Results A total of 242 patients completed the study. The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229. After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P < .001; PPS: mean difference -1.87, 95% CI -2.71 to -1.03, P < .001). FEV1, FVC, and FEV1%pred were significantly higher over time in the Xuan Bai Cheng Qi group compared with those in the control group (day 10, FAS and PPS: P < .05). PaO2 and PaCO2 were significantly improved in the Xuan Bai Cheng Qi group (day 10, FAS and PPS: P < .05). Xuan Bai Cheng Qi was also found to ameliorate cytokine levels and oxidation/antioxidant index compared with placebo. There were no differences in safety variables and adverse events between the two groups. Conclusions Xuan Bai Cheng Qi formula appears to be a

  1. Efficacy and Safety of Zhuanggu Joint Capsules in Combination with Celecoxib in Knee Osteoarthritis: A Multi-center, Randomized, Double-blind, Double-dummy, and Parallel Controlled Trial

    PubMed Central

    Zhang, Xian-Long; Yang, Jing; Yang, Liu; Liu, Jian-Guo; Cai, Xin-Yu; Fan, Wei-Ming; Yun, Xue-Qing; Ma, Jin-Zhong; Weng, Xi-Sheng

    2016-01-01

    Background: Knee osteoarthritis (KOA) is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling, stiffness, and movement disorders. The therapeutic goal is to alleviate or eliminate pain, correct deformities, improve or restore joint functions, and improve the quality of life. This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA. Methods: This multi-center, randomized, double-blind, double-dummy, parallel controlled trial, started from December 2011 to May 2014, was carried out in 6 cities, including Beijing, Shanghai, Chongqing, Changchun, Chengdu, and Nanjing. A total of 432 patients with KOA were divided into three groups (144 cases in each group). The groups were treated, respectively, with Zhuanggu joint capsules combined with celecoxib capsule simulants, Zhuanggu joint capsules combined with celecoxib capsules, and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively. The improvement of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment. Intergroup and intragroup comparisons of quantitative indices were performed. Statistically significant differences were evaluated with pairwise comparisons using Chi-square test (or Fisher's exact test) and an inspection level of α = 0.0167. Results: Four weeks after treatment, the total efficacies of Zhuanggu group, combination group, and celecoxib group were 65%, 80%, and 64%, respectively, with statistically significant differences among the three groups (P = 0.005). Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu (P = 0.005) and celecoxib (P = 0.003) groups. The difference between the latter two groups was not statistically

  2. Comparative assessment of the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult indian patients with osteoarthritis of the hip or knee: A 4-week, double-blind, randomized, comparative, multicenter study

    PubMed Central

    Goregaonkar, Arvind; Mathiazhagan, K.J.; Shah, Ravindra R.; Kapoor, Paramjeet Singh; Taneja, Praveen; Sharma, Akhilesh; Bolmall, Chandrashekhar; Baliga, Vidyagauri P.

    2009-01-01

    Background: Reports of cardiovascular adverse events (AEs) associated with the use of cyclooxygenase-2 inhibitors for the treatment of osteoarthritis (OA) have prompted the quest for a better-tolerated NSAID. Objective: The aim of this study was to compare the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult Indian patients with OA of the hip or knee. Methods: This 4-week, double-blind, randomized, comparative, multicenter study was undertaken to compare oral lornoxicam and diclofenac in patients with OA. Patients who met the selection criteria were enrolled consecutively from the outpatient clinics of each of the participating hospitals in India. Participants completed the Western Ontario and McMasters Individual Osteoarthritis Index (WOMAC-OA), WOMAC Composite Index (WOMAC-CI) (for pain, stiffness, and physical function), and a 10-cm visual analog scale (VAS) (0–10 where 0 = no pain and 10 = worst possible pain or severe or excruciating pain) at each study visit (weeks 0 [baseline], 2, and 4 [or at early termination]). Patients' and physicians' global assessments of arthritis control were measured at each study visit when laboratory and clinical AEs were also monitored. The primary end points were the WOMAC-OA, the WOMAC-CI, and VAS scores for pain among the patients who completed the study. Results: Of the 273 patients (159 men, 114 women; mean [SD] age, 44.73 [10.72] years; range, 28–68 years) enrolled in the study, 13 (7 in the lornoxicam group and 6 in the diclofenac group) were lost to follow-up and their effectiveness and tolerability results were not included in the study analysis. Over the 4-week study period, both drugs provided significant (P < 0.05) sustained relief of OA symptoms compared with baseline. Compared with baseline, the mean pain score (WOMAC-CI) decreased 90.6% (13.88 [4.47] vs 1.30 [1.49]; P < 0.05) in the lornoxicam group and 88.9% (14.15 [4.56] vs 1.57 [1.49]; P < 0.05) in the diclofenac group

  3. Swahili 12 Weeks Course.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This 12-weeks course in basic Swahili comprises 55 lesson units in five volumes. The general course format consists of (1) perception drills for comprehension, oral production, and association using "situational picture" illustrations; (2) dialogs in English and Swahili, with cartoon guides; (3) sequenced pattern and recombination drills, and (4)…

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

    PubMed

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

    2016-01-13

    Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-C(FX)) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits. PMID:26764156

  5. 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

  6. Comparative study of the efficacy and safety between blonanserin and risperidone for the treatment of schizophrenia in Chinese patients: A double-blind, parallel-group multicenter randomized trial.

    PubMed

    Li, Huafang; Yao, Chen; Shi, Jianguo; Yang, Fude; Qi, Shuguang; Wang, Lili; Zhang, Honggeng; Li, Jie; Wang, Chuanyue; Wang, Chuansheng; Liu, Cui; Li, Lehua; Wang, Qiang; Li, Keqing; Luo, Xiaoyan; Gu, Niufan

    2015-10-01

    This randomized, double-blind study compared the efficacy and safety of blonanserin and risperidone to treat Chinese schizophrenia patients aged ≥18 and < 65 years. Patients with Positive and Negative Syndrome Scale (PANSS) total scores ≥70 and ≤ 120 were randomized to receive blonanserin or risperidone using a gradual dose-titration method (blonanserin tablets: 8-24 mg/day; risperidone tablets: 2-6 mg/day), twice daily. Treatment populations consisted of 128 blonanserin-treated patients and 133 risperidone-treated patients. Intention-to-treat analysis was performed using the last observation carried forward method. Reductions of PANSS total scores by blonanserin and risperidone treatment were -30.59 and -33.56, respectively. Risperidone treatment was associated with elevated levels of serum prolactin (67.16% risperidone versus 52.31% blonanserin) and cardiac-related abnormalities (22.39% risperidone versus 12.31% blonanserin), and blonanserin patients were more prone to extrapyramidal side effects (48.46% blonanserin versus 29.10% risperidone). In conclusion, blonanserin was as effective as risperidone for the treatment of Chinese patients with schizophrenia. The overall safety profiles of these drugs are comparable, although blonanserin was associated with a higher incidence of EPS and risperidone was associated with a higher incidence of prolactin elevation and weight gain. Thus, blonanserin is useful for the treatment of Chinese schizophrenia patients. PMID:26343601

  7. 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

  8. A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

    PubMed Central

    Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

    2015-01-01

    Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

  9. Effects of Nutritional Supplementation on Fatigue, and Autonomic and Immune Dysfunction in Patients with End-Stage Renal Disease: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

    PubMed Central

    Fukuda, Sanae; Koyama, Hidenori; Kondo, Kazuhiro; Fujii, Hisako; Hirayama, Yoshinobu; Tabata, Tsutomu; Okamura, Mikio; Yamakawa, Tomoyuki; Okada, Shigeki; Hirata, Sumio; Kiyama, Hiroshi; Kajimoto, Osami; Watanabe, Yasuyoshi; Inaba, Masaaki; Nishizawa, Yoshiki

    2015-01-01

    Background Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment. We hypothesized that multinutritional support would improve quality of life, fatigue symptoms, and potential quantitative measures including endocrine, immune and autonomic functions in patients with ESRD undergoing hemodialysis. Methods Two hundred and two hemodialysis patients were randomly assigned to receive active treatment (containing vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, carnitine, coenzyme Q10, naïve galacto-oligosaccharide, and zinc) or placebo after each dialysis session for 12 weeks. The patients and attending physicians were blinded to the treatment, and 172 patients (86 in each group) completed the study. Fatigue was evaluated via fatigue questionnaire at 0, 4, and 12 weeks. To assess human herpes virus (HHV) 6 and 7 reactivation, numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12. Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography. Results Clinical characteristics, changes in fatigue, quality of life score, endocrine functions, and laboratory data did not differ significantly between the two groups. Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo. Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers. Similarly, HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance. Conclusions Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis. PMID:25746727

  10. A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D.

    PubMed

    Henriksen, Kim; Byrjalsen, Inger; Andersen, Jeppe R; Bihlet, Asger R; Russo, Luis A; Alexandersen, Peter; Valter, Ivo; Qvist, Per; Lau, Edith; Riis, Bente J; Christiansen, Claus; Karsdal, Morten A

    2016-10-01

    This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8mg/d) or placebo for 36months. The primary endpoint was the proportion of patients with a new vertebral fracture. The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (±0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (±0.12%) increase in the placebo group by the end of the study (p<0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24months, but not at 36months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected. Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related. Due to the lack of efficacy in preventing fractures, the development of the

  11. Dapagliflozin’s Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension

    PubMed Central

    Leiter, Lawrence A.; de Bruin, Tjerk W.A.; Gause-Nilsson, Ingrid; Sugg, Jennifer; Parikh, Shamik J.

    2015-01-01

    OBJECTIVE To assess the efficacy and safety of dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, compared with placebo in patients with type 2 diabetes (T2D), documented pre-existing cardiovascular disease (CVD), and a history of hypertension. RESEARCH DESIGN AND METHODS Patients (N = 922) were randomized to receive 10 mg dapagliflozin or placebo in a double-blind trial for 24 weeks, followed by a 28-week extension period. In patients receiving insulin, the insulin dose was reduced by 25% at randomization. Patients were stratified by age, insulin use, and time from the most recent qualifying cardiovascular (CV) event. Co-primary end points were a change from baseline in hemoglobin A1c (HbA1c) and the proportion of patients achieving a combined reduction in HbA1c of ≥0.5% (5.5 mmol/mol), body weight (BW) of ≥3%, and systolic blood pressure (SBP) of ≥3 mmHg. RESULTS At 24 weeks, dapagliflozin significantly reduced HbA1c (−0.38% [−4.2 mmol/mol]) from baseline (8.18%) compared with a slight increase with placebo from baseline (8.08%) (0.08% [0.9 mmol/mol]). Significantly more patients met the three-item end point with treatment with dapagliflozin than with placebo (11.7% vs. 0.9%, respectively). Changes were maintained over 52 weeks. Although ∼42% of patients were ≥65 years old, similar results were observed in both age-stratified groups. Serious adverse events, hypoglycemia, urinary tract infections, and cardiac disorders were similar between groups. Adverse events of hypotension, dehydration, hypovolemia, genital infection, and renal failure or impairment occurred more often with dapagliflozin treatment. CONCLUSIONS In this study that evaluated T2D patients who were at high risk for future CVD events, dapagliflozin administration had significantly greater effects in reducing HbA1c, BW, and SBP, without adversely impacting CV safety when compared with placebo treatment. PMID:25852208

  12. How "Blind" Are Double-Blind Studies?

    ERIC Educational Resources Information Center

    Margraf, Jurgen; And Others

    1991-01-01

    Compared alprazolam, imipramine, and placebo in the treatment of panic disorder patients (n=59) to investigate concerns about the internal validity of the double-blind design. Found that the great majority of patients and physicians were able to rate accurately whether active drug or placebo had been given and physicians could distinguish between…

  13. Efficacy and Tolerability of Conventional Nimesulide Versus Beta-Cyclodextrin Nimesulide in Patients with Pain After Surgical Dental Extraction: A Multicenter, Prospective, Randomized, Double-Blind, Double-Dummy Study☆

    PubMed Central

    Bocanegra, Mildred; Seijas, Alberto; Yibirín, Maria González

    2003-01-01

    Background: Pain following extraction of an impacted third molar is widely used to assess analgesic efficacy, especially that of a single dose of a drug. The analgesic activity of conventional nimesulide (CN) has been documented in a variety of types of acute and chronic pain. Beta-cyclodextrin nimesulide (BN) is a new formulation in which nimesulide is included in a cyclodextrin molecule, which increases its solubility in water and its dilution rate, allowing extended, rapid absorption of the drug. Objective: The aim of this study was to assess the efficacy and tolerability of a single dose of BN compared with CN in patients with pain following extraction of an impacted third molar. Methods: This was a prospective, randomized, double-blind, double-dummy study conducted at 3 dentistry centers in Venezuela. The patients were randomized to 1 of 2 groups. One group received a single dose of BN (400-mg tablet, equivalent to 100 mg of nimesulide); the other group received a single dose of CN (100-mg tablet). Both groups also received a placebo. The efficacy variables were (1) pain intensity (PI), assessed on a visual analog scale (VAS) at the following times: 0, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration; (2) time to first measurable difference in PI from baseline (PID) (PID ≥1 cm on the VAS; ie, the beginning of analgesic action); (3) maximum PID (max PID); (4) sum of PIDs in the 12-hour observation period; (5) pain relief (PR), as rated on a 5-point scale; (6) maximum PR; and (7) sum of the PR scores in the 12-hour observation period (ie, total PR). For the tolerability analysis, all adverse events (AEs) were to be recorded, and the investigators were to assess whether each AE was drug related. Results: Seventy-two patients were enrolled in the study. Of these, 62 patients (40 women, 22 men; mean [SD] age, 20.1 [5.9] years) were assessed; 35 were treated with BN and 27 with CN. PI reduction was more rapid and greater

  14. Soft-tissue injuries from sports activities and traffic accidents--treatment with low-level laser therapy: a multicenter double-blind placebo-controlled clinical study on 132 patients

    NASA Astrophysics Data System (ADS)

    Simunovic, Zlatko; Trobonjaca, Tatjana

    2000-06-01

    The aim of current multicenter clinical study was to assess the efficacy of low energy-level laser therapy (LLLT) in the treatment of soft tissue injuries compared to the placebo and classical phyiotherapeutic procedures. This clinical study was conducted in two centers located in Locarno, Switzerland and Opatija, Croatia. Two types of irradiation techniques were used: (1) direct, skin contact technique for treatment of trigger points where IR diode laser 830 nm continuous wave was applied; and (2) scanning technique for irradiation of larger surface area with use of Helium Neon laser 632.8 nm combined with IR diode laser 904 nm pulsed wave. Results were evaluated according to clinical parameters like: hematoma, swelling, heat, pan and loss of function. The findings were statistically analyzed via chi- square test. Results have demonstrated that the recovery process was accelerated in 85 percent of patients treated with LLLT compared to the control group of patients. The results and advantages obtained proved once again the efficacy of LLLT as a new and successful way to treat soft tissue injuries.

  15. Rationale and design of the 'F.I.R.E.' study. A multicenter, double-blind, randomized, placebo-controlled study to measure the effect of FX06 (a fibrin-derived peptide Bbeta(15-42)) on ischemia-reperfusion injury in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

    PubMed

    Atar, Dan; Huber, Kurt; Rupprecht, Hans-Jürgen; Kopecky, Stephen L; Schwitter, Jürg; Theek, Carmen; Brandl, Katherine; Henning, Rainer; Geudelin, Bernard

    2007-01-01

    Immediate reopening of acutely occluded coronary arteries via primary percutaneous coronary intervention (PCI) is the treatment of choice to salvage the ischemic myocardium in the setting of ST-segment elevation myocardial infarction (STEMI). However, the sudden re-initiation of blood flow achieved with PCI can lead to a local acute inflammatory response with further endothelial and myocardial damage. This phenomenon, described as 'reperfusion injury', has been recognized for several decades, yet no pharmacologic intervention has so far succeeded in reducing myocardial damage linked to reperfusion. FX06 is a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15-42)). It prevents leukocyte migration through the gap junctions of endothelial cells. Experimental studies have shown that FX06 inhibits the binding of the proinflammatory fibrin E1 fragment to VE-cadherin expressed in the adherence junction. It represents a novel approach to reducing local and systemic inflammation, including myocardial reperfusion injury, in the adherens junction. The present multicenter, double-blind, randomized, placebo-controlled study is designed to test the hypothesis that FX06 injection during and immediately after primary PCI can reduce infarct size in patients with STEMI. The primary outcome measure of efficacy in this study is the degree of myocardial salvage calculated as the difference between the perfusion defect before and after PCI, determined by myocardial perfusion scintigraphy during rest. Further, infarct size at the end of the index hospitalization, as well as at 4 months, will be measured by cardiac magnetic resonance imaging. The present position paper describes the rationale, design and the methods utilized in this trial. PMID:17019083

  16. Rationale and design of the RIACT–study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation. Methods/Design The RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited. Discussion It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy. Trial registration Clinical trials gov. number: NCT01117662 PMID:23101480

  17. Portuguese Special Course: 12 Weeks.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This 12-week course in beginning Portuguese comprises four volumes of student text (Lessons 1-55) and a fifth volume of Portuguese-English/English-Portuguese vocabulary. Lesson materials consist of basic dialogs with English translation, recombination dialogs, readings and comprehension questions, oral exercises, and in later units, additional…

  18. Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo

    PubMed Central

    Gao, Y; Guo, X; Han, P; Li, Q; Yang, G; Qu, S; Yue, L; Wang, C-N; Skljarevski, V; Dueñas, H; Raskin, J; Gu, L

    2015-01-01

    Background Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP. Methods This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient’s diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance. Results Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: −2.40, placebo: −1.97; LS mean change difference (95% confidence interval) = −0.43 (−0.82, −0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002). Conclusions Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials. PMID

  19. The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism

    ERIC Educational Resources Information Center

    Hyman, Susan L.; Stewart, Patricia A.; Foley, Jennifer; Cain, Usa; Peck, Robin; Morris, Danielle D.; Wang, Hongyue; Smith, Tristram

    2016-01-01

    To obtain information on the safety and efficacy of the gluten-free/casein-free (GFCF) diet, we placed 14 children with autism, age 3-5 years, on the diet for 4-6 weeks and then conducted a double-blind, placebo-controlled challenge study for 12 weeks while continuing the diet, with a 12-week follow-up. Dietary challenges were delivered via weekly…

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  1. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong).

    PubMed

    Park, Jin-Sun; Shin, Joon-Han; Hong, Taek-Jong; Seo, Hong-Seog; Shim, Wan-Joo; Baek, Sang-Hong; Jeong, Jin-Ok; Ahn, Youngkeun; Kang, Woong-Chol; Kim, Young-Hak; Kim, Sang-Hyun; Hyon, Min-Su; Choi, Dong-Hoon; Nam, Chang-Wook; Park, Tae-Ho; Lee, Sang-Chol; Kim, Hyo-Soo

    2016-01-01

    The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (-52.3% [2.8%] vs -0.6% [3.5%], P<0.0001), and the difference was -51.7% (4.1%) (95% confidence interval: -59.8% to -43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (-10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was -10.5 (1.8) mmHg (95% confidence interval: -14.1 to -6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large pill burden. PMID

  2. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong)

    PubMed Central

    Park, Jin-Sun; Shin, Joon-Han; Hong, Taek-Jong; Seo, Hong-Seog; Shim, Wan-Joo; Baek, Sang-Hong; Jeong, Jin-Ok; Ahn, Youngkeun; Kang, Woong-Chol; Kim, Young-Hak; Kim, Sang-Hyun; Hyon, Min-Su; Choi, Dong-Hoon; Nam, Chang-Wook; Park, Tae-Ho; Lee, Sang-Chol; Kim, Hyo-Soo

    2016-01-01

    The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (−52.3% [2.8%] vs −0.6% [3.5%], P<0.0001), and the difference was −51.7% (4.1%) (95% confidence interval: −59.8% to −43.6%). The least square mean change (standard error) from baseline in diastolic blood pressure 8 weeks after treatment was significantly greater in the FDC group than in the rosuvastatin group (−10.4 [1.2] mmHg vs 0.1 [1.6] mmHg, P<0.0001), and the difference was −10.5 (1.8) mmHg (95% confidence interval: −14.1 to −6.9 mmHg). There were 50 adverse events in 41 patients (22.7%) and eight adverse drug reactions in five patients (2.8%). The study found that FDC therapy with olmesartan medoxomil and rosuvastatin is an effective, safe treatment for patients with hypertension and dyslipidemia. This combination may improve medication compliance in patients with a large

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

    PubMed

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

    2016-09-01

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

  4. Treatment of Vertigo: A Randomized, Double-Blind Trial Comparing Efficacy and Safety of Ginkgo biloba Extract EGb 761 and Betahistine.

    PubMed

    Sokolova, Larysa; Hoerr, Robert; Mishchenko, Tamara

    2014-01-01

    A multicenter clinical trial was performed to compare the efficacy and safety of Ginkgo biloba extract EGb 761 and betahistine at recommended doses in patients with vertigo. One hundred and sixty patients (mean age 58 years) were randomly assigned to double-blind treatment with EGb 761 (240 mg per day) or betahistine (32 mg per day) for 12 weeks. An 11-point numeric analogue scale, the Vertigo Symptom Scale-short form, the Clinical Global Impression Scales and the Sheehan Disability Scale were used as outcome measures. Both treatment groups were comparable at baseline and improved in all outcome measures during the course of treatment. There was no significant intergroup difference with regard to changes in any outcome measure. Numerically, improvements of patients receiving EGb 761 were slightly more pronounced on all scales. Clinical global impression was rated "very much improved" or "much improved" in 79% of patients treated with EGb 761 and in 70% receiving betahistine. With 27 adverse events in 19 patients, EGb 761 showed better tolerability than betahistine with 39 adverse events in 31 patients. In conclusion, the two drugs were similarly effective in the treatment of vertigo, but EGb 761 was better tolerated. This trial is registered with controlled-trials.com ISRCTN02262139. PMID:25057270

  5. Treatment of Vertigo: A Randomized, Double-Blind Trial Comparing Efficacy and Safety of Ginkgo biloba Extract EGb 761 and Betahistine

    PubMed Central

    Sokolova, Larysa; Mishchenko, Tamara

    2014-01-01

    A multicenter clinical trial was performed to compare the efficacy and safety of Ginkgo biloba extract EGb 761 and betahistine at recommended doses in patients with vertigo. One hundred and sixty patients (mean age 58 years) were randomly assigned to double-blind treatment with EGb 761 (240 mg per day) or betahistine (32 mg per day) for 12 weeks. An 11-point numeric analogue scale, the Vertigo Symptom Scale—short form, the Clinical Global Impression Scales and the Sheehan Disability Scale were used as outcome measures. Both treatment groups were comparable at baseline and improved in all outcome measures during the course of treatment. There was no significant intergroup difference with regard to changes in any outcome measure. Numerically, improvements of patients receiving EGb 761 were slightly more pronounced on all scales. Clinical global impression was rated “very much improved” or “much improved” in 79% of patients treated with EGb 761 and in 70% receiving betahistine. With 27 adverse events in 19 patients, EGb 761 showed better tolerability than betahistine with 39 adverse events in 31 patients. In conclusion, the two drugs were similarly effective in the treatment of vertigo, but EGb 761 was better tolerated. This trial is registered with controlled-trials.com ISRCTN02262139. PMID:25057270

  6. Double-blind versus deceptive administration of a placebo.

    PubMed

    Kirsch, I; Weixel, L J

    1988-04-01

    Subjects were given varying doses of a placebo, consisting of decaffeinated coffee, with double-blind or deceptive instructions. Deceptive administration simulated clinical situations in that subjects were led to believe that they were receiving an active drug. In contrast, subjects in double-blind conditions were aware that they might receive a placebo. Double-blind and deceptive administration of the placebo produced different, and in some instances, opposite effects on pulse rate, systolic blood pressure, and subjective mood. Deceptive administration produced an increase in pulse rate, whereas double-blind administration did not. A theoretically predicted curvilinear effect on systolic blood pressure, alertness, tension, and certainty of having consumed caffeine was confirmed with deceptive administration, but not with double-blind administration. Double-blind administration produced curves in the opposite direction on each of these variables. The effects of the placebo on motor performance varied as a function of subject's beliefs about the effects of caffeine. These data challenge the validity of double-blind experimental designs and suggest that this common method of drug assessment may lead to spurious conclusions. PMID:3365327

  7. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials

    PubMed Central

    2010-01-01

    Background Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. Methods These studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day). Results No statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively). Conclusions Results of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy. Trial registration numbers ClinicalTrials.gov identifier: NCT00412100 and NCT00412152 PMID:20920236

  8. [Homeopathic treatment of adenoid vegetations. Results of a prospective, randomized double-blind study].

    PubMed

    Friese, K H; Feuchter, U; Moeller, H

    1997-08-01

    In a monocenter prospective randomized double-blind clinical trial the efficacy of homeopathic treatment was investigated on children with adenoid vegetations justifying an operation. Patients were treated with either homeopathic remedies such as Nux vomica D200, Okoubaka D3, Tuberculinum D200, Barium jodatum D4 and Barium jodatum D6 or with placebo. The duration of the study for each patient was 3 months. Examination of the ears using a microscope, rhinoscopy, stomatoscopy and pharyngoscopy, as well as tympanometry and audiometry were performed after 4, 8 and 12 weeks. Out of a total of 97 children studied between the ages of 4 to 10 years 82 could be analyzed. At the end of the study no operation was required in 70.7% of the placebo-treated children and in 78.1% of the children treated with homeopathic preparations. These results show no statistical significance. PMID:9378668

  9. Randomized, Double-Blind, Controlled Study of Losartan in Children with Proteinuria

    PubMed Central

    Lam, Chun; Loeys, Tom; Shahinfar, Shahnaz; Strehlau, Juergen; Wells, Thomas G.; Santoro, Emanuela; Manas, Denise; Gleim, Gilbert W.

    2010-01-01

    Background and objectives: No large, randomized, double-blind trials in children with proteinuria treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported. Design, setting, participants, & measurements: This 12-week, double-blind, multinational study investigated the effects of losartan 0.7 to 1.4 mg/kg per day compared with placebo (normotensive stratum) or amlodipine 0.1 to 0.2 mg/kg per day up to 5 mg/d (hypertensive stratum) on proteinuria (morning-void urinary protein-creatinine ratio, baseline ≥0.3 g/g) in 306 children up to 17 years of age. Results: Twelve weeks of treatment with losartan significantly reduced proteinuria compared with amlodipine/placebo: losartan −35.8% (95% confidence interval: −27.6% to −43.1%) versus amlodipine/placebo 1.4% (95% confidence interval: −10.3% to 14.5%), P ≤ 0.001. Significance remained after adjustment for differences across treatment groups in change in BP (losartan produced incremental systolic and diastolic BP reductions versus amlodipine of 5.4 and 4.6 mmHg, respectively; and versus placebo of 3.8 and 4.0 mmHg, respectively). Proteinuria reduction was consistently observed in the normotensive (−34.4% losartan; 2.6% placebo) and hypertensive (−41.5% losartan; 2.4% amlodipine) strata, and in all prespecified subgroups, including age, gender, race, Tanner stage, weight, prior therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, as well as among the most common etiologies of proteinuria. Adverse event incidence was low and comparable in all groups. Conclusions: Losartan significantly lowered proteinuria and was well tolerated after 12 weeks in children aged 1 to 17 years with proteinuria with or without hypertension, a population that has not previously been rigorously studied. PMID:20089489

  10. Adding Memantine to Rivastigmine Therapy in Patients With Mild-to-Moderate Alzheimer's Disease: Results of a 12-Week, Open-Label Pilot Study

    PubMed Central

    Riepe, Matthias W.; Adler, Georg; Ibach, Bernd; Weinkauf, Birgit; Gunay, Ibrahim; Tracik, Ferenc

    2006-01-01

    Objective: At present, inhibition of cholines-terase is the treatment of choice for subjects with mild-to-moderate Alzheimer's disease (AD). Memantine, a noncompetitive antagonist at N-methyl-d-aspartate receptors, is currently used to treat subjects with moderate-to-severe AD. The goal of this multicenter, open-label pilot study was to investigate whether combination therapy with memantine added to rivastigmine is safe and beneficial in subjects with mild-to-moderate AD. Method: Patients with a DSM-IV diagnosis of dementia of the Alzheimer's type (N = 95), who were treated with rivastigmine (6–12 mg/day) for a maximum duration of 24 weeks prior to baseline, received memantine (5–20 mg/day) in combination with rivastigmine for 12 weeks. The primary efficacy variable was the change in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score at the end of 12 weeks compared with baseline. The study was conducted between September 15, 2003, and May 27, 2004. Results: There was a statistically significant difference between baseline and week 12 for the ADAS-cog total score, showing a positive effect of combination therapy. Combination therapy did not evidence any unexpected safety concerns and was well-tolerated by most patients. Conclusion: Memantine in combination with rivastigmine appears to be safe and beneficial in patients with mild-to-moderate AD. Our results need to be confirmed in a large, long-term, randomized, double-blind, placebo-controlled clinical trial. PMID:17235381

  11. Randomized, Double-Blind, Dose-Ranging Study of TAK-875, a Novel GPR40 Agonist, in Japanese Patients With Inadequately Controlled Type 2 Diabetes

    PubMed Central

    Kaku, Kohei; Araki, Takahiro; Yoshinaka, Ryoji

    2013-01-01

    OBJECTIVE Assessment of the efficacy and safety of TAK-875 (a novel GPR40 agonist) in Japanese patients with type 2 diabetes inadequately controlled by diet/exercise. RESEARCH DESIGN AND METHODS This was a phase II, multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12-week dose-ranging evaluation of TAK-875 (6.25–200 mg once daily) with the primary end point of change in A1C at week 12. A nonblinded group received 1 mg glimepiride once daily as an active control. RESULTS A total of 396 patients were randomized to receive TAK-875 (n = 299), placebo (n = 48), or glimepiride (n = 49). The least square mean changes in A1C at week 12 from baseline were as follows: 0.09% in the placebo group; −0.54, −0.67, −0.88, −1.27, −1.29, and −1.40% in the 6.25-, 12.5-, 25-, 50-, 100-, and 200-mg TAK-875 groups, respectively; and −1.32% in the 1-mg glimepiride group. All TAK-875 groups had statistically significant reductions in A1C compared with placebo (P < 0.0001), and those receiving ≥50 mg TAK-875 achieved reductions in A1C equivalent to those with glimepiride. Results for other glycemic parameters, including improvements during a meal tolerance test, mirrored these positive findings with TAK-875. There were no significant differences in incidence of adverse events among the groups and no dose-dependent changes in tolerability. Hypoglycemic episodes were reported in 0.7% of patients in the TAK-875 groups and in 4.1% of the glimepiride group. CONCLUSIONS TAK-875 produced clinically and statistically significant improvements in glycemic control in patients with type 2 diabetes inadequately controlled by diet and exercise, and it was well tolerated with a lower propensity to cause hypoglycemia. PMID:23086138

  12. Can Acupuncture Treatment Be Double-Blinded? An Evaluation of Double-Blind Acupuncture Treatment of Postoperative Pain

    PubMed Central

    Vase, Lene; Baram, Sara; Takakura, Nobuari; Takayama, Miho; Yajima, Hiroyoshi; Kawase, Akiko; Schuster, Lars; Kaptchuk, Ted J.; Schou, Søren; Jensen, Troels Staehelin; Zachariae, Robert; Svensson, Peter

    2015-01-01

    Blinding protects against bias but the success of blinding is seldom assessed and reported in clinical trials including studies of acupuncture where blinding represents a major challenge. Recently, needles with the potential for double-blinding were developed, so we tested if acupuncture can be double-blinded in a randomized study of sixty-seven patients with acute pain ≥ 3 (0-10 scale following third molar removal) who received active acupuncture with a penetrating needle or placebo acupuncture with a non-penetrating needle. To test if acupuncture was administered double-blind, patients and acupuncturists were asked about perceived treatment allocation at the end of the study. To test if there were clues which led to identification of the treatment, deep dull pain associated with needle application and rotation (termed “de qi” in East Asian medicine), and patients’ pain levels were assessed. Perceived treatment allocation depended on actual group allocation (p < 0.015) for both patients and acupuncturists, indicating that the needles were not successful in double-blinding. Up to 68% of patients and 83% of acupuncturists correctly identified the treatment, but for patients the distribution was not far from 50/50. Also, there was a significant interaction between actual or perceived treatment and the experience of de qi (p = 0.027), suggesting that the experience of de qi and possible non-verbal clues contributed to correct identification of the treatment. Yet, of the patients who perceived the treatment as active or placebo, 50% and 23%, respectively, reported de qi. Patients’ acute pain levels did not influence the perceived treatment. In conclusion, acupuncture treatment was not fully double-blinded which is similar to observations in pharmacological studies. Still, the non-penetrating needle is the only needle that allows some degree of practitioner blinding. The study raises questions about alternatives to double-blind randomized clinical trials in

  13. A double-blind randomized control trial of diazepam

    PubMed Central

    1983-01-01

    A double-blind randomized controlled trial of diazepam against placebo in the management of minor conditions seen in general practice demonstrated that administration of either diazepam or placebo was associated with a substantial reduction in symptomatology three weeks later. There was no demonstrable difference between diazepam and placebo. PMID:6358487

  14. 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

  15. 100 positive double-blind studies: enough or too little?

    NASA Astrophysics Data System (ADS)

    Tuner, Jan; Hode, Lars

    2000-06-01

    A major argument among the opponents of laser therapy has been the absence of scientific documentation. This was a valid position in the 80s and partly in the 90s. But today, is this still a sound argument. There are more than 2,000 published studies in the field, including meeting abstracts and anecdotal reports. The vast majority of these papers reports positive effects of LLLT in vitro and in vivo. It is fair to argue that negative results are less prone to be published, but certainly more than 80 percent of the published studies are positive. In the field of dentistry, for instance, the positive percentage is well above 90 percent. The present literature study will look at the heart of the positive documentation: the positive double blind studies. It may come as a surprise to many critics that there are more than 100 positive double blind studies in the field laser therapy. This is a god base for a further understanding of the effects of low level laser in the clinical setting. We must, however, be as critical as the sceptics themselves in order to obtain a constructive dialogue between 'attorneys' and sceptics. In this paper, a critical review of 100 positive double blind studies will be presented.

  16. 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…

  17. Weight gain during a double-blind multidosage clozapine study.

    PubMed

    de Leon, Jose; Diaz, Francisco J; Josiassen, Richard C; Cooper, Thomas B; Simpson, George M

    2007-02-01

    Possible variables associated with weight gain during clozapine treatment include dosing, treatment duration, baseline body mass index (BMI), sex, and plasma norclozapine concentrations. Weight gains during a double-blind, randomized clozapine study using 100-, 300-, and 600-mg/d doses were analyzed. It was hypothesized that weight gain was associated with baseline BMI, clozapine dosing, and demographic factors. The possible contribution of plasma clozapine and norclozapine concentrations was explored. Fifty treatment-refractory schizophrenia patients were randomized to 100-, 300-, or 600-mg/d doses of clozapine for a 16-week, double-blind treatment in a research ward. Nonresponsive patients went onto a second and/or a third 16-week, double-blind treatment at the other doses. Weights of patients were measured every week. During the first clozapine treatment, weight gain varied across 3 baseline BMI categories (normal-weight patients [4.1 kg, P < 0.001], overweight patients [2.6 kg, P = 0.05], and obese patients [0.36 kg, not significant]) and according to dosing (600 mg/d [4.4 kg], 300 mg/d [2.6 kg], and 100 mg/d [1.3 kg]). Sex had no effect after controlling for baseline BMI and dose, but the African-American race had a strong significant effect despite the small number of African Americans (n = 6). At the end of the first clozapine treatment, plasma norclozapine concentration was not significantly correlated with weight gain in the total sample (r = 0.16, P = 0.32, n = 43), but seems to be strongly correlated in nonsmokers. Despite its limitations, this study indicates that baseline BMI, dosing, and, possibly, the African-American race may be major determinants of clozapine-induced weight gain. PMID:17224708

  18. Cinnarizine versus Topiramate in Prophylaxis of Migraines among Children and Adolescents: A Randomized, Double-Blind Clinical Trial

    PubMed Central

    ASHRAFI, Mahmoud Reza; NAJAFI, Zeinab; SHAFIEI, Masih; HEIDARI, Kazem; TOGHA, Mansoureh

    2014-01-01

    Objective Migraines, a common health problem in children and adolescents, still do not have an FDA approved preventive treatment for patients under the age of 18 years. This study compares and contrasts the efficacy and safety of cinnarizine and topiramate in preventing pediatric migraines. Materials & Methods In this randomized, double-blind clinical trial 44 migrainous (from 4–15 years of age) were equally allocated to receive cinnarizine or topiramate. The primary efficacy measure was monthly migraine frequency. Secondary efficacy measures were monthly migraine intensity and ≥ 50% responder rate. Efficacy measures were recorded at the baseline and at 4, 8, and 12 weeks of treatment. Results During the double-blind phase of the study, monthly migraine frequency and intensity were significantly decreased in both the cinnarizine and topiramate groups when compared to the baseline. However, at the end of the study, the cinnarizine group exhibits a significant decrease from the baseline in the mean monthly migraine intensity when compared to the topiramate group (4.7 vs. 3, respectively; 95% CI = -0.8 to -3.2). Conclusion No significant difference between cinnarizine and topiramate was found for the prevention of pediatric migraines. Both treatments were well tolerated. PMID:25657766

  19. Meige syndrome: double-blind crossover study of sodium valproate.

    PubMed Central

    Snoek, J W; van Weerden, T W; Teelken, A W; van den Burg, W; Lakke, J P

    1987-01-01

    A double-blind crossover study of sodium valproate and placebo was conducted in five patients with Meige syndrome. CSF neurotransmitter studies were performed at the end of each treatment period. GABA levels were not influenced by the administration of sodium valproate. An increase in HVA levels was observed in every patient, which may reflect an increase in central dopaminergic activity. This finding may explain the trend towards clinical deterioration which was observed during treatment with sodium valproate. Sodium valproate appears to be ineffective in Meige syndrome. PMID:3121795

  20. Effect of chocolate in migraine: a double-blind study

    PubMed Central

    Moffett, A. M.; Swash, M.; Scott, D. F.

    1974-01-01

    The effect of chocolate on a group of volunteer migrainous subjects, who had observed that headache regularly occurred after the ingestion of small amounts of cocoa products, was investigated. Two separate studies were carried out in a double-blind placebo controlled manner. Only 13 headaches occurred to chocolate alone in 80 subject sessions, and only two subjects responded consistently to chocolate in the two studies. This suggests that chocolate on its own is rarely a precipitant of migraine. Other possible implications of the results are also discussed. PMID:4838915

  1. Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial

    PubMed Central

    Tønnesen, Philip; Lauri, Hans; Perfekt, Roland; Mann, Karl; Batra, Anil

    2012-01-01

    A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (≥1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany. Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1% versus 16.1%; relative success rate (RR) 1.62, 95% CI 1.09–2.41), week 24 (15.7% versus 6.8%; RR 2.30, 95% CI 1.23–4.30), and week 52 (13.8% versus 5.6%; RR 2.48, 95% CI 1.24–4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active spray versus 71.4% with placebo spray. Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo. PMID:22323576

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Nagata, Eiichiro; Ogino, Mieko; Iwamoto, Kounosuke; Kitagawa, Yasuhisa; Iwasaki, Yasuo; Yoshii, Fumihito; Ikeda, Joh-E.

    2016-01-01

    Objective Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS. Design A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial. Methods The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7). The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint) and upon completion or discontinuation of the study (2nd endpoint) of the dosing. Results Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%), eating and drinking (P = 2.2%), ALSFRS-R total (P = 17.6%), grip strength (P = 19.8%) compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%), ALSAQ40-communication (P = 11.9%), eating and drinking (P = 13.6%), and neck forward-bent test (P = 15.4%) of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence. Conclusions BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment. Trial Registration UMIN Clinical Trials UMIN000008527 PMID:26910108

  4. Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women

    PubMed Central

    Thorup, Anne Cathrine; Lambert, Max Norman; Kahr, Henriette Strøm; Bjerre, Mette; Jeppesen, Per Bendix

    2015-01-01

    Objective. To investigate the effect by which daily consumption of a novel red clover (RC) extract influences bone health, inflammatory status, and cardiovascular health in healthy menopausal women. Design. A 12-week randomized, double-blinded, placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones (33.8 mg as aglycones) or placebo. Methods. Bone parameters were changes in bone mineral density (BMD), bone mineral content (BMC), and T-score at the lumbar spine and femoral neck. Bone turnover (CTx) and inflammatory markers were measured in plasma and finally blood pressure (BP) was evaluated. Results. RC extract had positive effect on bone health, and only the women receiving the placebo experienced a decline in BMD (p < 0.01) at the lumbar spine. T-score at the lumbar spine only decreased in the placebo group (p < 0.01). CTx decreased in the RC group with −9.94 (±4.93)%, although not significant. Conclusion. Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels. No changes in BP or inflammation markers were found and no side effects were observed. PMID:26265926

  5. Evaluation of the PPAR-γ Agonist Pioglitazone in Mild Asthma: A Double-Blind Randomized Controlled Trial

    PubMed Central

    Anderson, J. R.; Pang, L.; Smith, K. M; Bailey, H.; Hodgson, D. B.; Shaw, D. E.; Knox, A. J.; Harrison, T. W.

    2016-01-01

    Background Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial. Methods Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis. Results There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02). Conclusions We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma. Trial Registration ClinicalTrials.gov NCT01134835 PMID:27560168

  6. Double-blind comparison of piroxicam and indomethacin in the treatment of cervicobrachial syndrome and periarthritis scapulohumeralis (stiff shoulder).

    PubMed

    Yamamoto, M; Sugano, T; Kashiwazaki, S; Kageyama, T; Mizushima, Y; Kameyama, M

    1983-01-01

    In a 14-day double-blind multicenter trial the efficacy and safety of piroxicam was compared with that of indomethacin among patients with extra-articular rheumatic conditions marked by cervicobrachial pain. The drugs were found to have comparable overall efficacy, with over 75% of the patients in both drug groups experiencing some improvement. Piroxicam appeared to provide somewhat better results in the subpopulation with cervicobrachial syndrome, while indomethacin was marginally better among patients with periarthritis scapulohumeralis. There was a trend toward better relief of nighttime pain with piroxicam in the cervicobrachial syndrome group at week 2. Fewer adverse reactions were observed with piroxicam, and the number of patients discontinued for side effects was also lower for piroxicam (4.1%) than for indomethacin (9.5%). PMID:6391931

  7. Progesterone and the premenstrual syndrome: a double blind crossover trial.

    PubMed Central

    Dennerstein, L; Spencer-Gardner, C; Gotts, G; Brown, J B; Smith, M A; Burrows, G D

    1985-01-01

    A double blind, randomised, crossover trial of oral micronised progesterone (two months) and placebo (two months) was conducted to determine whether progesterone alleviated premenstrual complaints. Twenty three women were interviewed premenstrually before treatment and in each month of treatment. They completed Moos's menstrual distress questionnaire, Beck et al's depression inventory, Spielberger et al's state anxiety inventory, the mood adjective checklist, and a daily symptom record. Analyses of data found an overall beneficial effect of being treated for all variables except restlessness, positive moods, and interest in sex. Maximum improvement occurred in the first month of treatment with progesterone. Nevertheless, an appreciably beneficial effect of progesterone over placebo for mood and some physical symptoms was identifiable after both one and two months of treatment. Further studies are needed to determine the optimum duration of treatment. PMID:3924191

  8. Double blind study of ispaghula in irritable bowel syndrome.

    PubMed

    Prior, A; Whorwell, P J

    1987-11-01

    A double blind placebo controlled trial of ispaghula husk in 80 patients with irritable bowel syndrome is reported. Global assessment judged treatment to be satisfactory in 82% of patients receiving ispaghula and 53% of the placebo group (p less than 0.02). Bowel habit was unchanged in the placebo group, while constipation significantly improved in patients taking ispaghula (p = 0.026). Transit time decreased significantly in those taking ispaghula compared with placebo (p = 0.001), especially in patients with initially high transit times. Abdominal pain and bloating improved in both groups, with no significant differences between ispaghula and placebo. Four of the eight withdrawals on ispaghula and 10 of the 15 withdrawals on placebo were because of treatment failure. Ispaghula significantly improves overall well being in patients with irritable bowel syndrome, and in those with constipation favourably affects bowel habit and transit time. PMID:3322956

  9. Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5

    PubMed Central

    Fizazi, Karim; Jones, Robert; Oudard, Stephane; Efstathiou, Eleni; Saad, Fred; de Wit, Ronald; De Bono, Johann; Cruz, Felipe Melo; Fountzilas, George; Ulys, Albertas; Carcano, Flavio; Agarwal, Neeraj; Agus, David; Bellmunt, Joaquim; Petrylak, Daniel P.; Lee, Shih-Yuan; Webb, Iain J.; Tejura, Bindu; Borgstein, Niels; Dreicer, Robert

    2015-01-01

    Purpose Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods In our study, 1,099 men were randomly assigned in a 2:1 schedule to receive orteronel 400 mg plus prednisone 5 mg twice daily or placebo plus prednisone 5 mg twice daily, stratified by region (Europe, North America [NA], and non-Europe/NA) and Brief Pain Inventory–Short Form worst pain score. Primary end point was overall survival (OS). Key secondary end points (radiographic progression-free survival [rPFS], ≥ 50% decrease of prostate-specific antigen [PSA50], and pain response at 12 weeks) were to undergo statistical testing only if the primary end point analysis was significant. Results The study was unblinded after crossing a prespecified OS futility boundary. The median OS was 17.0 months versus 15.2 months with orteronel-prednisone versus placebo-prednisone (hazard ratio [HR], 0.886; 95% CI, 0.739 to 1.062; P = .190). Improved rPFS was observed with orteronel-prednisone (median, 8.3 v 5.7 months; HR, 0.760; 95% CI, 0.653 to 0.885; P < .001). Orteronel-prednisone showed advantages over placebo-prednisone in PSA50 rate (25% v 10%, P < .001) and time to PSA progression (median, 5.5 v 2.9 months, P < .001) but not pain response rate (12% v 9%; P = .128). Adverse events (all grades) were generally more frequent with orteronel-prednisone, including nausea (42% v 26%), vomiting (36% v 17%), fatigue (29% v 23%), and increased amylase (14% v 2%). Conclusion Our study did not meet the primary end point of OS. Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity. PMID:25624429

  10. Cognitive and mood effects in healthy children during 12 weeks' supplementation with multi-vitamin/minerals.

    PubMed

    Haskell, Crystal F; Scholey, Andrew B; Jackson, Philippa A; Elliott, Jade M; Defeyter, Margaret A; Greer, Joanna; Robertson, Bernadette C; Buchanan, Tom; Tiplady, Brian; Kennedy, David O

    2008-11-01

    Adequate levels of vitamins and minerals are essential for optimal neural functioning. A high proportion of individuals, including children, suffer from deficiencies in one or more vitamins or minerals. This study investigated whether daily supplementation with vitamins/minerals could modulate cognitive performance and mood in healthy children. In this randomised, double-blind, placebo-controlled, parallel groups investigation, eighty-one healthy children aged from 8 to 14 years underwent laboratory assessments of their cognitive performance and mood pre-dose and at 1 and 3 h post-dose on the first and last days of 12 weeks' supplementation with a commercially available vitamins/mineral product (Pharmaton Kiddi). Interim assessments were also completed at home after 4 and 8 weeks at 3 h post-dose. Each assessment comprised completion of a cognitive battery, delivered over the Internet, which included tasks assessing mood and the speed and accuracy of attention and aspects of memory (secondary, semantic and spatial working memory). The vitamin/mineral group performed more accurately on two attention tasks: 'Arrows' choice reaction time task at 4 and 8 weeks; 'Arrow Flankers' choice reaction time task at 4, 8 and 12 weeks. A single task outcome (Picture Recognition errors) evinced significant decrements at 12 weeks. Mood was not modulated in any interpretable manner. Whilst it is possible that the significant improvements following treatment were due to non-significant numerical differences in performance at baseline, these results would seem to suggest that vitamin/mineral supplementation has the potential to improve brain function in healthy children. This proposition requires further investigation. PMID:18507881

  11. Evaluation of a crataegus-based multiherb formula for dyslipidemia: a randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Hu, Miao; Zeng, Weiwei; Tomlinson, Brian

    2014-01-01

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

  12. 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

  13. Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial

    PubMed Central

    Na, Lixin; Zhang, Qiao; Jiang, Shuo; Du, Shanshan; Zhang, Wei; Li, Ying; Sun, Changhao; Niu, Yucun

    2015-01-01

    Our previous studies have shown that mangiferin decreased serum triglycerides and free fatty acids (FFAs) by increasing FFAs oxidation in both animal and cell experiments. This study sought to evaluate the effects of mangiferin on serum lipid profiles in overweight patients with hyperlipidemia. Overweight patients with hyperlipidemia (serum triglyceride ≥ 1.70 mmol/L, and total cholesterol ≥ 5.2 mmol/L) were included in this double-blind randomized controlled trial. Participants were randomly allocated to groups, either receiving mangiferin (150 mg/day) or identical placebo for 12 weeks. The lipid profile and serum levels of mangiferin, glucose, L-carnitine, β-hydroxybutyrate, and acetoacetate were determined at baseline and 12 weeks. A total of 97 participants completed the trial. Compared with the placebo control, mangiferin supplementation significantly decreased the serum levels of triglycerides and FFAs, and insulin resistance index. Mangiferin supplementation also significantly increased the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, β-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase activity. However, there were no differences in the serum levels of total cholesterol, low-density lipoprotein cholesterol, serum glucose, and insulin between groups. Mangiferin supplementation could improve serum lipid profiles by reducing serum triglycerides and FFAs in overweight patients with hyperlipidemia, partly due to the promotion of FFAs oxidation. PMID:25989216

  14. Mirtazapine in comorbid major depression and an alcohol use disorder: A double-blind placebo-controlled pilot trial.

    PubMed

    Cornelius, Jack R; Chung, Tammy; Douaihy, Antoine B; Kirisci, Levent; Glance, Jody; Kmiec, Julie; FitzGerald, Douglas; Wesesky, Maribeth A; Salloum, Ihsan

    2016-08-30

    This was a first double-blind, placebo-controlled pilot study to evaluate the efficacy of the novel antidepressant medication mirtazapine for treating both the depressive symptoms and the level of alcohol consumption of subjects with comorbid major depressive disorder and an alcohol use disorder (MDD/AUD). The results of two previous studies of mirtazapine in MDD/AUD subjects had suggested efficacy for mirtazapine for decreasing their level of depressive symptoms, but level of alcohol consumption had not been assessed in those studies. All subjects in this 12-week pilot study were randomized to either mirtazapine or placebo, and also received motivational enhancement therapy. Between-group analyses involving the outcome measures of depressive symptoms, level of alcohol consumption, and level of alcohol craving indicated no significant differences between groups, possibly because of limited sample size. However, within-group t tests in the mirtazapine group showed a significant decrease in depressive symptoms by week 2, also noted at all subsequent assessments (weeks 3, 4, 6, 8, 10, and 12) during the 12-week study. In contrast, no significant decrease in depressive symptoms was noted in the placebo group until week 8. No evidence of efficacy was found for mirtazapine for decreasing level of alcohol consumption in MDD /AUD subjects. PMID:27327217

  15. Effect of Kaempferia parviflora Extract on Physical Fitness of Soccer Players: A Randomized Double-Blind Placebo-Controlled Trial

    PubMed Central

    Promthep, Kreeta; Eungpinichpong, Wichai; Sripanidkulchai, Bungorn; Chatchawan, Uraiwan

    2015-01-01

    Background Physical fitness is a fundamental prerequisite for soccer players. Kaempferia parviflora is an herbal plant that has been used in some Asian athletes with the belief that it might prevent fatigue and improve physical fitness. This study aimed to determine the effects of Kaempferia parviflora on the physical fitness of soccer players. Material/Methods Sixty soccer players who routinely trained at a sports school participated in a double-blind placebo-controlled trial and were randomly allocated to the treatment group or the placebo group. The participants in both groups were given either 180 mg of Kaempferia parviflora extract in capsules or a placebo once daily for 12 weeks. Baseline data were collected using the following 6 tests of physical performance: a sit-and-reach test, a hand grip strength test, a back-and-leg strength test, a 40-yard technical test, a 50-metre sprint test, and a cardiorespiratory fitness test. All of the tests were performed every 4 weeks throughout the 12-week study period. Results The study showed that after treatment with Kaempferia parviflora, the right-hand grip strength was significantly increased at weeks 4, 8, and 12. The left-hand grip strength was significantly increased at week 8. However, the back-and-leg strength, the 40-yard technical test, the sit-and-reach test, the 50-metre sprint test, and the cardiorespiratory fitness test results of the treatment group were not significantly different from those of the placebo group. Conclusions Taking Kaempferia parviflora supplements for 12 weeks may significantly enhance some physical fitness components in soccer players. PMID:25957542

  16. Ozone treatment of recurrent aphthous stomatitis: a double blinded study

    PubMed Central

    AL-Omiri, Mahmoud K.; Alhijawi, Mohannad; AlZarea, Bader K.; Abul Hassan, Ra’ed S.; Lynch, Edward

    2016-01-01

    This study aimed to evaluate the use of ozone to treat recurrent aphthous stomatitis (RAS). Consecutive sixty-nine participants with RAS were recruited into this non-randomized double blind, controlled cohort observational study (test group). A control group of 69 RAS patients who matched test group with age and gender was recruited. RAS lesions in test group were exposed to ozone in air for 60 seconds while controls received only air. Ulcer size and pain were recorded for each participant at baseline and daily for 15 days. Ulcer duration was determined by recording the time taken for ulcers to disappear. The main outcome measures were pain due to the ulcer, ulcer size and ulcer duration. 138 RAS participants (69 participants and 69 controls) were analyzed. Ulcer size was reduced starting from the second day in test group and from the fourth day in controls (p ≤ 0.004). Pain levels were reduced starting from the first day in the test group and from the third day in controls (p ≤ 0.001). Ulcer duration, ulcer size after day 2 and pain levels were more reduced in the test group. In conclusion, application of ozone on RAS lesions for 60 seconds reduced pain levels and enhanced ulcers’ healing by reducing ulcers’ size and duration. PMID:27301301

  17. Clobetasone treatment of allergic conjunctivitis: a comparative double blind study.

    PubMed

    Cerqueti, P M; Prosio, P E; Bosia, S; Buscaglia, S; Ciprandi, G

    1993-01-01

    Glucocorticosteroids are often included in the treatment of allergic conjunctivitis. The present study compares the efficacy on clinical and cytological parameters and safety of topical clobetasone butyrate compared to placebo. The trial, designed as double blind, randomized and parallel group treatment, was carried out in 30 patients, suffering from seasonal allergic conjunctivitis due to Grass pollen, during the pollen season (June 1992). Patients received clobetasone butyrate 0.1% eye drops or placebo eye drops, two drops each eye, t.i.d. for 10 days. The clinical and cytological evidences were investigated on admission and at the end of treatment by clinicians and by patients on a dairy card. The steroid group showed a rapid and significant clinical improvement and at the end of the trial a statistically significant difference was evidenced between the active drug treated group and placebo treated group. No serious side effects were observed. The results show the clinical efficacy of clobetasone butyrate in the treatment of pollen-induced allergic conjunctivitis. PMID:8337991

  18. Treatment of nickel dermatitis with Antabuse; a double blind study.

    PubMed

    Kaaber, K; Menné, T; Veien, N; Hougaard, P

    1983-07-01

    A double blind, placebo-controlled treatment with Antabuse was carried out in 24 patients with hand eczema and nickel allergy. The amount of Antabuse given was gradually increased from 50 to 200 mg daily. The maximum dose was given for 6 weeks. During the treatment period, the dermatitis of 5 out of 11 patients in the group treated with Antabuse healed, compared with 2 out of 13 in the group receiving the placebo. A statistical analysis was made of changes observed during the study, through the parameters: scaling, frequency of flares, erythema, area involved and number of vesicles. Differences in results obtained with Antabuse and the placebo were statistically significant only for the parameters scaling and frequency of flares (p less than 0.05). The difference between the sums of parameters following the 2 forms of treatment was not statistically significant (p = 0.11). 2 patients treated with Antabuse showed signs of hepatic toxicity; 1 of them had toxic hepatitis. No other significant side effects were seen. PMID:6352169

  19. 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

  20. 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

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

    PubMed Central

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

    2015-01-01

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

  2. Efficacy of Olibra: A 12-Week Randomized Controlled Trial and a Review of Earlier Studies

    PubMed Central

    Rebello, Candida J; Martin, Corby K; Johnson, William D; O'Neil, Carol E; Greenway, Frank L

    2012-01-01

    Background Intervention strategies that harness the body's appetite and satiety regulating signals provide a means of countering excessive energy intake. Methods Eighty-two subjects were enrolled (18–60 years, body mass index: 25–40 kg/m2) in a randomized, placebo-controlled, double-blind, parallel trial. During a 12-week period, the effects of Olibra™ fat emulsion (2.1 g twice daily) on food intake, appetite, satiety, weight, and body composition were compared with those of a twice daily administered placebo (1.95 g milk fat). On days -7, 0, and 28, Olibra or the placebo added to 200 g of yogurt was served at breakfast and lunch. Food intake, appetite, and satiety were assessed after lunch and dinner. Body weight was measured on days -7, 0, 14, 28, 56, and 84. Body fat, waist circumference, and waist-hip ratio were determined on days 0 and 84. The Eating Inventory was administered at screening and on day 28. Data relating to 71 subjects were analyzed using analysis of covariance. Results At 12 weeks, body weight was reduced in the test group (2.17 ± 0.46 kg standard error of the mean, p < .0001) and the control group (1.68 ± 0.42 kg, p < .0001). Waist circumference decreased by 2.93 ± 0.85 cm in the test group (p = .001) and by 1.78 ± 0.74 cm in the control group (p = .02). Differential weight and waist circumference reductions were not significant. Hunger scores (Eating Inventory) decreased more in the test group (p = .0082). Differential group effects were not significant for body fat, waist-hip ratio, food intake, appetite, and satiety. Conclusions At this dose, Olibra did not exert a consistent effect on food intake, appetite regulation, body weight, or body composition. PMID:22768902

  3. Aspartame Sensitivity? A Double Blind Randomised Crossover Study

    PubMed Central

    Sathyapalan, Thozhukat; Thatcher, Natalie J.; Hammersley, Richard; Rigby, Alan S.; Pechlivanis, Alexandros; Gooderham, Nigel J.; Holmes, Elaine; le Roux, Carel W.; Atkin, Stephen L.; Courts, Fraser

    2015-01-01

    Background Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. Methods This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Results Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Conclusion Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies

  4. Chinese herbal medicine for obesity: a randomized, double-blinded, multicenter, prospective trial.

    PubMed

    Zhou, Qiang; Chang, Bai; Chen, Xin-Yan; Zhou, Shui-Ping; Zhen, Zhong; Zhang, Lan-Lan; Sun, Xin; Zhou, Yuan; Xie, Wan-Qing; Liu, Hong-Fang; Xu, Yuan; Kong, Yi; Zhou, Li-Bo; Lian, Feng-Mei; Tong, Xiao-Lin

    2014-01-01

    Obesity is a serious medical problem worldwide. As a holistic therapy, traditional Chinese medicine (TCM) may have a potential in obesity management. In this controlled trial, we evaluated the safety and effectiveness of xin-ju-xiao-gao-fang (XJXGF), a TCM herbal formulation, in 140 obese subjects over a 24-week period. The XJXGF formula mainly consists of rhubarb, coptis, semen cassia, and citrus aurantium. Subjects with body mass index (BMI) 28-40 kg/m(2) were recruited at 5 centers in China. We assessed the changes in subjects' body weight, its related parameters, and the reduction of insulin resistance (IR) after administration of XJXGF formula or low-dose XJXGF (10% of the XJXGF formula, as control). After 24-week treatment, among participants in the XJXGF formula group and low-dose XJXGF group, the mean ± SE changes in the body weight were -3.58 ± 0.48 and -1.91 ± 0.38 kg, respectively (p < 0.01). The changes in the IR-index of two groups were -2.65 ± 1.04 and -1.58 ± 1.3, respectively (p < 0 .05). There were no serious adverse events reported during the 24-week trial. Participants reported 7 minor adverse events, 4 in the XJXGF formula group and 3 in the low-dose XJXGF group (p = 0.578). Future studies are needed to investigate the clinical utility of this TCM formulation in the treatment of obese subjects. PMID:25406653

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

    PubMed Central

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

    2012-01-01

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

  6. Chocolate flavanols and skin photoprotection: a parallel, double-blind, randomized clinical trial

    PubMed Central

    2014-01-01

    Background Solar ultraviolet (UV) radiation has deleterious effects on the skin, including sunburn, photoaging and cancer. Chocolate flavanols are naturally-occurring antioxidant and anti-inflammatory molecules that could play a role in preventing cutaneous UV damage. We investigated the influence of 12-week high-flavanol chocolate (HFC) consumption on skin sensitivity to UV radiation, measured by minimal erythema dose (MED). We also evaluated skin elasticity and hydration. Methods In this 2-group, parallel, double-blind, randomized controlled trial, 74 women aged 20–65 years and Fitzpatrick skin phototypes I or II were recruited from the general community in Quebec City, for randomization to either HFC (n = 33) or low-flavanol chocolate (LFC) (n = 41). A blocked randomisation (4), considering date of entry, skin type and age as factors, generated a sequentially-numbered allocation list. Study participants and research assistants were blinded. Totally, 30 g of chocolate were consumed daily for 12 weeks, followed by a 3-week washout period. MED was assessed at baseline and at 6, 9, 12 and 15 weeks. Main outcome was changes in MED at week 12. Results 33 participants in the HFC group and 41 in the LFC group were analyzed with 15 weeks of follow-up. Both groups showed similarly-increased MED at 12 weeks (HFC: 0.0252 ± 0.1099 J/cm2 [mean ± standard deviation (SD)]; LFC: 0.0151 ± 0.1118; mean difference (MD): 0.0100 J/cm2; 95% confidence interval (CI): -0.0417 to 0.0618). However, after 3-week washout, the HFC group presented decreased MED (-0.0248 ± 0.1145) whereas no effect was seen in the LFC group (0.0168 ± 0.1698) (MD: -0.0417; 95% CI: -0.1106 to 0.0272). Net temple elasticity increased slightly but significantly by 0.09 ± 0.12 mm in the HFC group at 12 weeks compared to 0.02 ± 0.12 mm in the LFC group (MD: 0.06; 95% CI: 0.01 to 0.12 ). No significant adverse events were reported. Conclusion Our study failed to

  7. Cardiac effects of sertindole and quetiapine: analysis of ECGs from a randomized double-blind study in patients with schizophrenia.

    PubMed

    Nielsen, Jimmi; Matz, Jørgen; Mittoux, Aurelia; Polcwiartek, Christoffer; Struijk, Johannes J; Toft, Egon; Kanters, Jørgen K; Graff, Claus

    2015-03-01

    The QT interval is the most widely used surrogate marker for predicting TdP; however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a quantitative T-wave morphology combination score (MCS) have emerged. This study investigated the cardiac effects of sertindole and quetiapine using the QTc interval and newer surrogate markers. Data were derived from a 12 week randomized double-blind study comparing flexible dosage of sertindole 12-20mg and quetiapine 400-600mg in patients with schizophrenia. ECGs were recorded digitally at baseline and after 3, 6 and 12 weeks. Between group effects were compared by using a mixed effect model, whereas assessment within group was compared by using a paired t-test. Treatment with sertindole was associated with QTcF and QTcB interval prolongation and an increase in MCS, T-wave asymmetry, T-wave flatness and TpTe. The mean increase in QTcF from baseline to last observation was 12.1ms for sertindole (p<0.001) and -0.5ms for quetiapine (p=0.8). Quetiapine caused no increase in MCS, T-wave asymmetry, T-wave flatness or TpTe compared to baseline. In the categorical analysis, there were 11 patients (9.6%) receiving quetiapine who experienced more than 20ms QTcF prolongation compared with 36 patients (33.3%) in the sertindole group. Sertindole (12-20mg) was associated with moderate QTc prolongation and worsening of T-wave morphology in a study population of patients with schizophrenia. Although, quetiapine (400-600mg) did not show worsening of repolarization measures some individual patients did experience significant worsening of repolarization. Clinical Trials NCT00654706. PMID:25583364

  8. Progesterone Reduces Cocaine Use in Postpartum Women with a Cocaine Use Disorder: A Randomized,Double-Blind Study

    PubMed Central

    Yonkers, Kimberly Ann; Forray, Ariadna; Nich, Charla; Carroll, Kathleen M.; Hine, Cristine; Merry, Brian C.; Shaw, Howard; Shaw, Julia; Sofuoglu, Mehmet

    2014-01-01

    Background Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). Methods A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. Findings Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. Interpretation These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. Funding US National Institute on Drug Abuse; Veterans Administration PMID:25328863

  9. 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

  10. 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

  11. Albendazole treatment of HIV-1 and helminth co-infection: A randomized, double blind, placebo-controlled trial

    PubMed Central

    Walson, Judd L.; Otieno, Phelgona A.; Mbuchi, Margaret; Richardson, Barbra A.; Lohman-Payne, Barbara; Macharia, Steve Wanyee; Overbaugh, Julie; Berkley, James; Sanders, Eduard J.; Chung, Michael; John-Stewart, Grace C.

    2009-01-01

    OBJECTIVE Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1 infected adults impacted markers of HIV-1 disease progression. DESIGN To date there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. METHODS A randomized, double-blind, placebo-controlled trial of albendazole (400mg daily for three days) in antiretroviral-naïve HIV-1 infected adults (CD4 >200 cells/mm3) with soil-transmitted helminth infection was conducted at ten sites in Kenya (Clinical Trials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. RESULTS Of 1,551 HIV-1 infected individuals screened for helminth-infection, 299 were helminth-infected. 234 adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 count was 557 cells/mm3 and mean plasma viral load was 4.75 log10 copies/mL at enrolment. Albendazole therapy resulted in significantly higher CD4 counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow up (+109 cells/mm3; 95% CI +38.9 to +179.0, p=0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (p=0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. CONCLUSIONS Treatment of A. lumbricoides with albendazole in HIV-1 co-infected adults resulted in significantly increased CD4 counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression. PMID:18670219

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

    PubMed Central

    Harandi, A. A.; Abolfazli, R.; Hatemian, A.; Ghragozlee, K.; Ghaffar-Pour, M.; Karimi, M.; Shahbegi, S.; Pakdaman, H.; Tabasi, M.; Tabatabae, A. L.; Nourian, A.

    2011-01-01

    Objective. To investigate the safety and efficacy of MLC601 (NeuroAid) as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 3 month) ischemic stroke. All patients were given either MLC601 (100 patients) or placebo (50 patients), 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P > .05). Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P < .001). Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases. PMID:21776364

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

    PubMed

    Harandi, A A; Abolfazli, R; Hatemian, A; Ghragozlee, K; Ghaffar-Pour, M; Karimi, M; Shahbegi, S; Pakdaman, H; Tabasi, M; Tabatabae, A L; Nourian, A

    2011-01-01

    Objective. To investigate the safety and efficacy of MLC601 (NeuroAid) as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 3 month) ischemic stroke. All patients were given either MLC601 (100 patients) or placebo (50 patients), 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P > .05). Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P < .001). Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases. PMID:21776364

  14. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial

    PubMed Central

    Borges, Cynthia M.; Papadimitriou, Alexandros; Duarte, Diego A.; Lopes de Faria, Jacqueline M.; Lopes de Faria, José B.

    2016-01-01

    Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect. PMID:27320846

  15. Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group.

    PubMed Central

    Bräutigam, M.; Nolting, S.; Schopf, R. E.; Weidinger, G.

    1995-01-01

    OBJECTIVE--To compare the efficacy and tolerability of terbinafine and itraconazole in the treatment of toenail tinea unguium. DESIGN--Multicentre, double blind, parallel group study. SETTING--17 university hospitals, one army hospital, and five dermatology practices. PATIENTS--195 patients with clinically suspected toenail tinea and growth of dermatophytes in baseline culture; data on 86 patients in the terbinafine group and 84 patients in the itraconazole group were fully evaluated for efficacy. INTERVENTIONS--Daily dose of 250 mg terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40 weeks. MAIN OUTCOME MEASURES--Mycological cure (negative results on microscopy and culture) and clinical improvement (length and area of unaffected nail) at week 52 or at discontinuation of treatment. RESULTS--At the end of the study mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of 84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of 86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (2P < 0.05). CONCLUSION--Terbinafine is more effective than itraconazole in the treatment of toenail tinea infection. PMID:7580551

  16. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial.

    PubMed

    Borges, Cynthia M; Papadimitriou, Alexandros; Duarte, Diego A; Lopes de Faria, Jacqueline M; Lopes de Faria, José B

    2016-01-01

    Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect. PMID:27320846

  17. Effects of Semelil (ANGIPARS™) on diabetic peripheral neuropathy: A randomized, double-blind Placebo-controlled clinical trial

    PubMed Central

    Bakhshayeshi, S.; Madani, SP.; Hemmatabadi, M.; Heshmat, R.; Larijani, B.

    2011-01-01

    Background and the purpose of the study Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARS™), a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. Methods In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARS™ and placebo groups). All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. Results Michigan diabetic neuropathy score was decreased notably in ANGIPARS™ group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARS™ group. Conclusion The results showed limited evidence of efficacy of ANGIPARS™ in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required. PMID:22615641

  18. Role of silicone derivative plus onion extract gel in presternal hypertrophic scar protection: a prospective randomized, double blinded, controlled trial.

    PubMed

    Jenwitheesuk, Kamonwan; Surakunprapha, Palakorn; Jenwitheesuk, Kriangsak; Kuptarnond, Chusak; Prathanee, Sompop; Intanoo, Worawit

    2012-08-01

    Use of silicone derivative and onion extract had been reported in the prevention of hypertrophic scarring. Our experience showed the preventive use of silicone derivative plus onion extract gel on hypertrophic scars after median sternotomy. In a randomized, double blinded, placebo-controlled study, 60 patients after median sternotomy incisions were separated into two groups. All patients were treated either with silicone derivative plus onion extract gel (Cybele(®) scagel) or placebo gel twice daily for a total treatment period of 12 weeks. During each visit, pain and itching scores were graded by the patients and scar characteristics were observed by surgeons using the Vancouver scar scale. Pain and itch score values from patients' who applied silicone derivative plus onion extract gel was less than another group (P < 0·05). Pigmentation was significantly different between two groups (P < 0·05) and the reduction of scores on vascularity, pliability, height in treated group was not superior to the untreated group. No adverse events were reported by any of the patients. A silicone derivative plus onion extract gel is safe and effective for the preventing the hypertrophic scarring after median sternotomy. PMID:22168750

  19. Mentha longifolia syrup in secondary amenorrhea: a double-blind, placebo-controlled, randomized trials

    PubMed Central

    2012-01-01

    Background Amenorrhea is defined as the cessation of menses. Hormone therapy is the most common treatment. Due to the contraindications and side effects of it and the increasing demand for alternative medicine substitutes, Mentha longifolia L. was used in this study. Mentha longifolia L. is a known medication in Iranian traditional medicine to induce menstrual bleeding in women with secondary amenorrhea and oligomenorrhea. Methods A double-blind, randomized, placebo-controlled, multicenter study was conducted in 120 women with secondary amenorrhea and oligomenorrhea. Treatment consisted of sequential oral syrup, 45 ml (15 ml three times a day) for 2 weeks. If the patients did not have menstruation after 2 weeks of taking the medication, we would wait for two more weeks. If the patients had menstruation at each stage of using the drug, we started it one week after the end of menstruation. But if the patients had not menstruate after four weeks (two-week using of drug and waiting for two more weeks), the previous steps were repeated. The drug and placebo were repeated in three cycles of menstruation. Bleeding was documented by the patient on diary cards. The primary outcome variable was the occurrence (yes/no) of bleeding during the first treatment cycle. The secondary efficacy outcome was the regularity of bleeding pattern during the three cycles of the study. Results The number of women with bleeding during the first cycle were higher in the drug group as in the placebo group (68.3% vs. 13.6%; p < 0.001). The regularity of bleeding throughout the study was markedly better in the drug group compared with those given placebo (33.3% vs. 3.3%; p < 0.001). No notable complication or side effect was reported in relation to Mentha longifolia L. syrup. Conclusion In conclusion, Mentha longifolia L. syrup is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with secondary amenorrhea and oligomenorrhea. PMID

  20. 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

  1. 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

  2. A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis

    PubMed Central

    Kirwan, J; Hallgren, R; Mielants, H; Wollheim, F; Bjorck, E; Persson, T; Book, C; Bowman, S; Byron, M; Cox, N; Field, M; Kanerud, L; Leirisalo-Repo, M; Malaise, M; Mohammad, A; Palmer, R; Petersson, I; Ringertz, B; Sheldon, P; Simonsson, M; Snowden, N; Van den Bosch, F

    2004-01-01

    Objectives: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. Methods: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. Results: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. Conclusions: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment. PMID:15140776

  3. Effect of Hydroxychloroquine Treatment on Dry Eyes in Subjects with Primary Sjögren’s Syndrome: a Double-Blind Randomized Control Study

    PubMed Central

    2016-01-01

    The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028). PMID:27366013

  4. Effect of Hydroxychloroquine Treatment on Dry Eyes in Subjects with Primary Sjögren's Syndrome: a Double-Blind Randomized Control Study.

    PubMed

    Yoon, Chang Ho; Lee, Hyun Ju; Lee, Eun Young; Lee, Eun Bong; Lee, Won-Woo; Kim, Mee Kum; Wee, Won Ryang

    2016-07-01

    The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028). PMID:27366013

  5. Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial.

    PubMed

    Heinälä, P; Alho, H; Kiianmaa, K; Lönnqvist, J; Kuoppasalmi, K; Sinclair, J D

    2001-06-01

    Several studies have shown the opioid antagonist naltrexone to be effective when combined with psychosocial therapies for the treatment of patients who are dependent on alcohol with fixed medication and time (12 weeks). In this study, 121 nonabstinent outpatients with alcohol dependence (DSM-IV) were treated with sessions of cognitive coping skills (N = 67) or supportive therapy (N = 54) and either naltrexone 50 mg/day (N = 63) or placebo (N = 58) daily for the first 12 weeks and thereafter for 20 weeks only when craving alcohol (i.e., targeted medication) in a prospective one-center, dual, double-blind, randomized clinical trial. The dropout rate for all subjects was 16.5% during the first 12-week period and approximately twice that level by the end of the study. There were no significant group differences in study completion and therapy participation rates. After the continuous medication (12 weeks), the coping/naltrexone group had the best outcome, and coping/placebo had the worst. This difference remained during the targeted medication period (the following 20 weeks). Naltrexone was not better than placebo in the supportive groups, but it had a significant effect in the coping groups: 27% of the coping/naltrexone patients had no relapses to heavy drinking throughout the 32 weeks, compared with only 3% of the coping/placebo patients. The authors' data confirm the original finding of the efficacy of naltrexone in conjunction with coping skills therapy. In addition, their data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking. PMID:11386491

  6. Fixed combination of cinnarizine and dimenhydrinate versus betahistine dimesylate in the treatment of Ménière's disease: a randomized, double-blind, parallel group clinical study.

    PubMed

    Novotný, Miroslav; Kostrica, Rom

    2002-01-01

    In a randomized, double-blind clinical study, we evaluated the efficacy and tolerability of the fixed combination of cinnarizine, 20 mg, and dimenhydrinate, 40 mg (Arlevert [ARL]) in comparison to betahistine dimesylate (12 mg) in 82 patients suffering from Ménière's disease for at least 3 months and showing the characteristic triad of symptoms (paroxysmal vertigo attacks, cochlear hearing loss, and tinnitus). The treatment (one tablet three times daily) extended to 12 weeks, with control visits at 1, 3, 6, and 12 weeks after drug intake. The study demonstrated for both the fixed-combination ARL and for betahistine a highly efficient reduction of vertigo symptoms in the course of the 12 weeks of treatment; however, no statistically significant difference between the two treatment groups could be established. Similar results were found for tinnitus (approximately 60% reduction) and for the associated vegetative symptoms (almost complete disappearance). Vestibulospinal reactions, recorded by means of craniocorpography, also improved distinctly, with a statistically significant superiority of ARL versus betahistine (p < .042) for the parameter of lateral sway (Unterberger's test). The caloric tests (electronystagmography) showed only minor changes for both treatment groups in the course of the study. A statistically significant improvement of hearing function of the affected ear (p = .042) was found for the combination preparation after 12 weeks of treatment. The tolerability was judged by the vast majority of patients (97.5%) in both groups to be very good. Only one patient (betahistine group) reported a nonserious adverse event, and two betahistine patients did not complete the study. In conclusion, the combination preparation proved to be a highly efficient and safe treatment option for Ménière's disease and may be used both in the management of acute episodes and in long-term treatment. Efficacy and safety were found to be similar to the widely used standard

  7. Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration.

    PubMed

    Ke, Yuyong; Labrie, Fernand; Gonthier, Renaud; Simard, Jean-Nicolas; Bergeron, Danielle; Martel, Céline; Vaillancourt, Mario; Montesino, Marlene; Lavoie, Lyne; Archer, David F; Balser, John; Moyneur, Erick

    2015-11-01

    The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G) were measured by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17 pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1-S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values. The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause. PMID:26291918

  8. Intravaginal Misoprostol for Cervical Ripening and Labor Induction in Nulliparous Women: A Double-blinded, Prospective Randomized Controlled Study

    PubMed Central

    Zhang, Yu; Zhu, Hao-Ping; Fan, Jian-Xia; Yu, Hong; Sun, Li-Zhou; Chen, Lian; Chang, Qing; Zhao, Nai-Qing; Di, Wen

    2015-01-01

    Background: In China, no multicenter double-blinded prospective randomized controlled study on labor induction has been conducted till now. This study is to evaluate the efficacy and safety of intravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women. Methods: This was a double-blinded, prospective randomized controlled study including nulliparous women from 6 university hospitals across China. Subjects were randomized into misoprostol or placebo group with the sample size ratio set to 7:2. Intravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h (repeated up to 3 times) for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes. Results: A total of 173 women for misoprostol group and 49 women for placebo were analyzed. The incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h was higher in the misoprostol group than in the placebo (64.2% vs. 22.5%, relative risk [RR]: 2.9, 95% confidence interval [CI]: 1.4–6.0). The incidence of onset of labor within 24 h was significantly higher in the misoprostol group than in the placebo group (48.0% vs. 18.4%, RR: 2.6, 95% CI: 1.2–5.7); and the induction-onset of labor interval was significantly shorter in the misoprostol group (P = 0.0003). However, there were no significant differences in the median process time of vaginal labor (6.4 vs. 6.8 h; P = 0.695), incidence (39.3% vs. 49.0%, RR: 0.8, 95% CI: 0.4–1.5) and indications (P = 0.683) of cesarean section deliveries, and frequencies of maternal, fetal/neonatal adverse events between the groups. Conclusion: Intravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening. PMID:26481739

  9. Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Munasinghe, Sujeeva A.; Oliff, Carolyn; Finn, Judith; Wray, John A.

    2010-01-01

    To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating…

  10. Human norovirus inactivation in oysters by high hydrostatic pressure processing: A randomized double-blinded study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This randomized, double-blinded, clinical trial assessed the effect of high hydrostatic pressure processing (HPP) on genogroup I.1 human norovirus (HuNoV) inactivation in virus-seeded oysters when ingested by subjects. The safety and efficacy of HPP treatments were assessed in three study phases wi...

  11. Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

    ERIC Educational Resources Information Center

    Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

    2004-01-01

    Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

  12. [Double-blind-study on treatment with clobetasol-17-propionate and other topical corticoids (author's transl)].

    PubMed

    Beck, M; Berger, C; Filipp, N; Hundertmark, U; Loewel, R

    1981-08-15

    90 patients suffering from chronic skin diseases-mainly psoriasis vulgaris-were treated in a double-blind-study for two weeks with topical Clobetasol-17-propionate compared with other topical corticoids. In 81% was seen a better therapeutical effect on the Clobetasol-17-propionate treated skin area. PMID:7027655

  13. EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

    ERIC Educational Resources Information Center

    Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

    2013-01-01

    Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

  14. Diclofenac versus dipyrone in acute renal colic: a double-blind controlled trial.

    PubMed

    Miralles, R; Camí, J; Gutiérrez, J; Torné, J; Garcés, J M; Badenas, J M

    1987-01-01

    A randomized, double-blind clinical trial in 50 patients was done to compare the efficacy and tolerance of single doses of intramuscular diclofenac 75 mg and dipyrone 2 g in acute renal colic. Both drugs were equally effective, but diclofenac was better in terms of complete relief of pain. Vital signs were affected according to the stress and pain. PMID:3322848

  15. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial.

    PubMed

    Zenico, T; Cicero, A F G; Valmorri, L; Mercuriali, M; Bercovich, E

    2009-04-01

    Lepidium meyenii (Maca) is a cultivated root belonging to the brassica family used in the Andean region for its supposed aphrodisiac properties. We carried out a double-blind clinical trial on 50 Caucasian men affected by mild erectile dysfunction (ED), randomised to treatment with Maca dry extract, 2400 mg, or placebo. The treatment effect on ED and subjective well-being was tested administrating before and after 12 weeks the International Index of Erectile Function (IIEF-5) and the Satisfaction Profile (SAT-P). After 12 weeks of treatment, both Maca- and placebo-treated patients experienced a significant increase in IIEF-5 score (P < 0.05 for both). However, patients taking Maca experienced a more significant increase than those taking placebo (1.6 +/- 1.1 versus 0.5 +/- 0.6, P < 0.001). Both Maca- and placebo-treated subjects experienced a significant improvement in psychological performance-related SAT-P score, but the Maca group higher than that of placebo group (+9 +/- 6 versus +6 +/- 5, P < 0.05). However, only Maca-treated patients experienced a significant improvement in physical and social performance-related SAT-P score compared with the baseline (+7 +/- 6 and +7 +/- 6, both P < 0.05). In conclusion, our data support a small but significant effect of Maca supplementation on subjective perception of general and sexual well-being in adult patients with mild ED. PMID:19260845

  16. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial

    PubMed Central

    Takwale, A; Tan, E; Agarwal, S; Barclay, G; Ahmed, I; Hotchkiss, K; Thompson, J R; Chapman, T; Berth-Jones, J

    2003-01-01

    Objective To study the efficacy and tolerability of borage oil, which contains a high concentration of γ linolenic acid, in children and adults with atopic eczema. Design Single centre, randomised, double blind, placebo controlled, parallel group trial. Setting Acute district general hospital in Nuneaton, England. Participants 151 patients, of whom 11 failed to return for assessment, leaving an evaluable population of 140 (including 69 children). Intervention Adults received four capsules of borage oil twice daily (920 mg γ linolenic acid), and children received two capsules twice daily, for 12 weeks. Main outcome measures Change in total sign score at 12 weeks measured with the six area, six sign, atopic dermatitis (SASSAD) score (primary endpoint); symptom scores, assessed on visual analogue scales; topical corticosteroid requirement, assessed on a five point scale; global assessment of response by participants; adverse events and tolerability. Results The mean SASSAD score fell from 30 to 27 in the borage oil group and from 28 to 23 in the placebo group. The difference between the mean improvements in the two groups was 1.4 (95% confidence interval -2.2 to 5.0) points in favour of placebo (P = 0.45). No significant differences occurred between treatment groups in the other assessments. Subset analysis of adults and children did not indicate any difference in response. The treatments were well tolerated. Conclusion γ linolenic acid is not beneficial in atopic dermatitis. PMID:14670885

  17. Comparison of chloroxylenol 0.5% plus salicylic acid 2% cream and benzoyl peroxide 5% gel in the treatment of acne vulgaris: a randomized double-blind study.

    PubMed

    Boutli, F; Zioga, M; Koussidou, T; Ioannides, D; Mourellou, O

    2003-01-01

    A 12-week double-blind randomized study was performed to compare benzoyl peroxide 5% (BP) gel and chloroxylenol 0.5% plus salicylic acid 2% (PCMX + SA) cream (Nisal cream) for efficacy and adverse reactions. Thirty-seven volunteers participated in the study, 19 in the BP group and 18 in the PCMX + SA group. The patients applied the medication twice daily to the entire face. Clinical evaluation and lesion counts were obtained at 0, 3, 6, 9 and 12 weeks. At week 12 both groups showed a marked improvement in both inflammatory and noninflammatory lesions (60% and 54% for the BP group and 62% and 56% for and 56% for the PCMX + SA group, respectively). Although PCMX + SA showed a slightly stronger keratolytic effect throughout the study period, there was no statistically significant difference in the reduction of the papulopustules or comedones between the two groups. Adverse effects such as erythema and photosensitivity were significantly fewer in the PCMX + SA group at week 12 (p = 0.0002 and p = 0.05, respectively). These results suggest that PCMX + SA cream is as effective as BP gel in the treatment of papulopustular and comedonal acne and that it is better tolerated. PMID:14708455

  18. Amitriptyline 2% cream vs. capsaicin 0.75% cream in the treatment of painful diabetic neuropathy (Double blind, randomized clinical trial of efficacy and safety).

    PubMed

    Kiani, Javad; Ahmad Nasrollahi, Saman; Esna-Ashari, Farzaneh; Fallah, Puyan; Sajedi, Firuzeh

    2015-01-01

    Because of less systemic side effects of topical medications in pain relief of the painful form of diabetic peripheral neuropathy, this study aimed to compare the effect of amitriptyline and capsaicin cream in relieving pain in this condition. In this randomized, double-blind and non -inferiority trial, 102 patients received amitriptyline 2% and capsaicin 0.75% creams 3 times a day for 12 weeks on the feet. Pain relief was measured by the visual analog scale (0-10). Treatment responding was considered as cure rate greater than 50% from baseline. Evaluations of the pain severity, compliance and drugs adverse effects were performed at each of the 4-week follow -up visits. Both drugs significantly relieved pain in 12 weeks compared with baseline values (P < 0.001 for both). Treatment responders were similar in both groups (P = 0.545). Intention-To-Treat analysis showed no significant difference in the efficacy between the two treatments (P = 0.703). Adverse events were more common in capsaicin group (P = 0.001). Dermatologic complications were the most common: itching, blister formation and erythema in the capsaicin group and skin dryness and itching in the amitriptyline group. This study demonstrates the similar efficacy of amitriptyline cream with capsaicin cream in managing diabetic neuropathic pain with fewer side effects. PMID:26664395

  19. 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

  20. 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

  1. Reduction of left ventricular mass by short-term antihypertensive treatment with isradipine: a double-blind comparison with enalapril.

    PubMed

    Galderisi, M; Celentano, A; Garofalo, M; Tammaro, P; Oliviero, M; Petrocelli, A; de Divitiis, O

    1994-06-01

    The aim of the present study was to evaluate the effect of dihydropyridine calcium antagonist isradipine on left ventricular (LV) structure and function in patients with essential hypertension. Cuff blood pressure and Doppler echocardiographic variables were assessed in 26 patients with mild to moderate hypertension (diastolic blood pressure range 95-110 mmHg) before and after 12 weeks of therapy with either isradipine 5 mg daily or enalapril 20 mg daily. The study was of double-blind, parallel design, with a placebo run-in period of 15 days. Three subjects withdrew from isradipine treatment because of flushing and 2 from enalapril treatment due to cough before completing the study. Both drugs significantly reduced cuff systolic and diastolic blood pressure (p < 0.001) without affecting heart rate. By virtue of the decrease in both septal wall (p < 0.01) and posterior wall thicknesses (p < 0.05), isradipine treatment produced a significant reduction in LV mass adjusted for height (p < 0.001) in comparison with placebo; also LV end-systolic dimension showed a slight decrease (p < 0.05). Enalapril induced a similar reduction in LV end-systolic dimension (p < 0.05) but the changes of wall thickness and LV mass did not reach statistical significance. In conclusion, our results indicate that isradipine treatment improves LV systolic function and causes a significant reduction in LV mass. This reduction is observed early in the course of antihypertensive treatment and is effective in both patients with and without LV hypertrophy. PMID:7921533

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

    PubMed

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

    2016-07-01

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

  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. Effect of radial shock wave therapy for carpal tunnel syndrome: A prospective randomized, double-blind, placebo-controlled trial.

    PubMed

    Wu, Yung-Tsan; Ke, Ming-Jen; Chou, Yu-Ching; Chang, Chih-Ya; Lin, Ching-Yueh; Li, Tsung-Ying; Shih, Feng-Mei; Chen, Liang-Cheng

    2016-06-01

    Three recent studies demonstrated the positive effect of extracorporeal shock wave therapy (ESWT) for treating carpal tunnel syndrome (CTS). However, none have entirely proved the effects of ESWT on CTS because all studies had a small sample size and lacked a placebo-controlled design. Moreover, radial ESWT (rESWT) has not been used to treat CTS. We conducted a prospective randomized, controlled, double-blinded study to assess the effect of rESWT for treating CTS. Thirty-four enrolled patients (40 wrists) were randomized into intervention and control groups (20 wrists in each). Participants in the intervention group underwent three sessions of rESWT with nightly splinting, whereas those in the control group underwent sham rESWT with nightly splinting. The primary outcome was visual analog scale (VAS), whereas the secondary outcomes included the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), cross-sectional area (CSA) of the median nerve, sensory nerve conduction velocity of the median nerve, and finger pinch strength. Evaluations were performed before treatment and at 1, 4, 8, and 12 weeks after the third rESWT session. A significantly greater improvement in the VAS, BCTQ scores, and CSA of the median nerve was noted in the intervention group throughout the study as compared to the control group (except for BCTQ severity at week 12 and CSA at weeks 1 and 4) (p < 0.05). This is the first study to assess rESWT in a randomized placebo-controlled trial and demonstrate that rESWT is a safe and effective method for relieving pain and disability in patients with CTS. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:977-984, 2016. PMID:26610183

  5. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    PubMed

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids. PMID:25993547

  6. A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis.

    PubMed

    Naito, Yuji; Yamaguchi, Shinnichi; Mori, Yasuhiro; Nakajima, Kouji; Hashimoto, Sanshiro; Tomaru, Masakazu; Satoh, Yoshihiko; Hitomi, Yuji; Karita, Masakazu; Hiwatashi, Tomoaki; Kawahito, Yutaka; Yoshikawa, Toshikazu

    2013-07-01

    Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA. PMID:23874073

  7. Label-free, single molecule resonant cavity detection: a double-blind experimental study.

    PubMed

    Chistiakova, Maria V; Shi, Ce; Armani, Andrea M

    2015-01-01

    Optical resonant cavity sensors are gaining increasing interest as a potential diagnostic method for a range of applications, including medical prognostics and environmental monitoring. However, the majority of detection demonstrations to date have involved identifying a "known" analyte, and the more rigorous double-blind experiment, in which the experimenter must identify unknown solutions, has yet to be performed. This scenario is more representative of a real-world situation. Therefore, before these devices can truly transition, it is necessary to demonstrate this level of robustness. By combining a recently developed surface chemistry with integrated silica optical sensors, we have performed a double-blind experiment to identify four unknown solutions. The four unknown solutions represented a subset or complete set of four known solutions; as such, there were 256 possible combinations. Based on the single molecule detection signal, we correctly identified all solutions. In addition, as part of this work, we developed noise reduction algorithms. PMID:25785307

  8. Label-Free, Single Molecule Resonant Cavity Detection: A Double-Blind Experimental Study

    PubMed Central

    Chistiakova, Maria V.; Shi, Ce; Armani, Andrea M.

    2015-01-01

    Optical resonant cavity sensors are gaining increasing interest as a potential diagnostic method for a range of applications, including medical prognostics and environmental monitoring. However, the majority of detection demonstrations to date have involved identifying a “known” analyte, and the more rigorous double-blind experiment, in which the experimenter must identify unknown solutions, has yet to be performed. This scenario is more representative of a real-world situation. Therefore, before these devices can truly transition, it is necessary to demonstrate this level of robustness. By combining a recently developed surface chemistry with integrated silica optical sensors, we have performed a double-blind experiment to identify four unknown solutions. The four unknown solutions represented a subset or complete set of four known solutions; as such, there were 256 possible combinations. Based on the single molecule detection signal, we correctly identified all solutions. In addition, as part of this work, we developed noise reduction algorithms. PMID:25785307

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

    PubMed Central

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

    2010-01-01

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

  10. Echinacea/sage or chlorhexidine/lidocaine for treating acute sore throats: a randomized double-blind trial

    PubMed Central

    2009-01-01

    Background The aim of this trial was to assess the relative efficacy of a sage/echinacea spray and a chlorhexidine/lidocaine spray in the treatment of acute sore throats. Methods This was a multicenter, randomized, double-blind, double-dummy controlled trial carried out in eleven general practices in Switzerland. A total of 154 patients (133 analyzed in per protocol collective) at least 12 years old with acute sore throat present for not more than 72 hours prior to inclusion and with a throat score ≥6 participated in the study. They used either an echinacea/sage spray or a chlorhexidine/lidocaine spray with two puffs every 2 hours, in a double-dummy blinded manner, up to 10 times daily until they were symptom-free, for a maximum of 5 days. The main outcome measures was the comparison of response rates during the first three days. A response was defined as a decrease of at least 50% of the total symptoms compared to baseline. Results The echinacea/sage treatment exhibited similar efficacy to the chlorhexidine/lidocaine treatment in reducing sore throat symptoms during the first 3 days (P(x < Y) = .5083). Response rates after 3 days were 63.8% in the echinacea/sage group and 57.8% in the chlorhexidine/lidocaine group. For all secondary parameters, such as time to becoming symptom free, throat pain, and global assessments of efficacy by the physician and patient, no difference between the two treatments was seen. They were both very well tolerated. Conclusion An echinacea/sage preparation is as efficacious and well tolerated as a chlorhexidine/lidocaine spray in the treatment of acute sore throats. PMID:19748859

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

    PubMed Central

    McGraw, Thomas

    2016-01-01

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

  12. 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

  13. The Clinical Efficacy of Mometasone Furoate in Multi-Lamellar Emulsion for Eczema: A Double-blinded Crossover Study

    PubMed Central

    Kim, Duk Han; Lee, Hyun Jong; Park, Chun Wook; Kim, Kyu Han; Lee, Kwang Hoon; Ro, Byung In

    2013-01-01

    Background Topical application of corticosteroids also has an influence on skin barrier impairment. Physiological lipid mixtures, such as multi-lamellar emulsion (MLE) containing a natural lipid component leads to effective recovery of the barrier function. Objective The purpose of this study was to conduct an evaluation of the therapeutic efficacy and skin barrier protection of topical mometasone furoate in MLE. Methods A multi-center randomized, double-blind, controlled study was performed to assess the efficacy and safety of mometasone furoate cream in MLE for Korean patients with eczema. The study group included 175 patients with eczema, who applied either mometasone furoate in MLE cream or methylprednisolone aceponate cream for 2 weeks. Treatment efficacy was evaluated using the physician's global assessment of clinical response (PGA), trans-epidermal water loss (TEWL), and visual analogue scale (VAS) for pruritus. Patients were evaluated using these indices at days 4, 8, and 15. Results Comparison of PGA score, TEWL, and VAS score at baseline with those at days 4, 8, and 15 of treatment showed a significant improvement in both groups. Patients who applied mometasone furoate in MLE (74.8%) showed better results (p<0.05) than those who applied methylprednisolone aceponate (47.8%). The TEWL improvement ratio was higher in the mometasone furoate in MLE group than that in the methylprednisolone aceponate group, and VAS improvement was also better in the mometasone furoate in MLE group. Conclusion Mometasone furoate in MLE has a better therapeutic efficacy as well as less skin barrier impairment than methylprednisolone aceponate. PMID:23467551

  14. A Randomized, Double-blind, Vehicle-controlled Trial of Luliconazole Cream 1% in the Treatment of Interdigital Tinea Pedis

    PubMed Central

    Vlahovic, Tracey C.; Gold, Michael H.; Parish, Lawrence Charles; Korotzer, Andrew

    2014-01-01

    Objective: To evaluate the efficacy and safety of luliconazole cream 1% applied once daily for 14 days in patients with interdigital tinea pedis. Design: Multicenter, randomized, double-blind, parallel-group, vehicle-controlled study. Setting: Private dermatology clinics and clinical research centers in the United States and Central America. Participants: Three hundred twenty-two male and female patients ≥12 years of age diagnosed with interdigital tinea pedis. Measurements: Complete clearance (i.e., clinical and mycological cure), effective treatment, and fungal culture and susceptibility. Results: At study Day 42, complete clearance was obtained by a larger percentage (14.0% [15/107] vs. 2.8% [3/107]; p<0.001) of patients treated with luliconazole cream 1% compared with vehicle. Also at Day 42, more luliconazole-treated patients compared with vehicle-treated patients obtained effective treatment (32.7% vs. 15.0%), clinical cure (15.0% vs. 3.7%), and mycologic cure (56.1% vs. 27.1%). Erythema, scaling, and pruritus scores were lower for the luliconazole cream 1% group compared with vehicle on Day 14, Day 28, and Day 42. For all species and the same isolates, the MIC50/90 for luliconazole cream 1% was 6- to 12-fold lower than for other agents tested. No patients discontinued treatment because of a treatment-emergent adverse event. Conclusion: Luliconazole cream 1% was safe and well-tolerated and demonstrated significantly greater efficacy than vehicle cream in patients with interdigital tinea pedis. PMID:25371767

  15. A double-blind trial of chronic cerebellar stimulation in twelve patients with severe epilepsy.

    PubMed Central

    Wright, G D; McLellan, D L; Brice, J G

    1984-01-01

    Twelve patients with severe intractable epilepsy were treated by chronic cerebellar stimulation under double-blind conditions for six months. No reduction in seizure frequency occurred that could be attributed to stimulation, though eleven of the patients considered that the trial had helped them. One patient experienced fewer episodes of incontinence during stimulation. Cerebellar stimulation in its present form cannot be recommended for the treatment of severe intractable epilepsy. PMID:6381652

  16. A Double-Blind Randomized Pilot Study Comparing Quetiapine and Divalproex for Adolescent Mania

    ERIC Educational Resources Information Center

    Delbello, Melissa P.; Kowatch, Robert A.; Adler, Caleb M.; Stanford, Kevin E.; Welge, Jeffrey A.; Barzman, Drew H.; Nelson, Erik; Strakowski, Stephen M.

    2006-01-01

    Objective: To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania. Method: Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 [micro]g/mL) for 28 days for this double-blind study,…

  17. ["Sham Needle"--Design and Application of A Double-blind Placebo Needle Assembly].

    PubMed

    Yan, Liu; Ma, Li-hong

    2016-02-01

    The blind study design, particularly the double-blind study design is a very important method for diminishing placebo effect and reducing bias in clinical medical trial. Enlightened by Streitberger's and Park's sham needle design, the authors of the present paper introduce a newly designed sham needle device (Yan's sham-needle) for controlled double-blind trials of acupuncture. This sham needle device consists of needle, tube and base. The bottom of the tube is completely sealed and it can never arouse any invasive stimulation on the subject's skin when the sham needle is downward pressed on the body surface. Meanwhile, this sham device is filled with sponge which is able to simulate soft tissues of the acupoint area. By combining words suggestions or hints before trials and the same shape as verum device, this sham-needle device reduces the risk of blind-breaking and makes it possible to conduct controlled double-blind trials. Primary practice showed that this device may provide a new and practical tool for researching the placebo effect of acupuncture therapy. PMID:27141628

  18. Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo-controlled trial

    PubMed Central

    Gommoll, Carl; Chen, Dalei; Nunez, Rene; Khan, Arif

    2015-01-01

    Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder (MDD) treatment in adults. This was a 10-week, multicenter, double-blind, placebo-controlled and active-controlled, fixed-dose trial (NCT01473381). Adult patients with MDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision criteria) were randomized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day, citalopram 40 mg/day, or placebo. Primary efficacy: Montgomery–Åsberg Depression Rating Scale (MADRS); secondary efficacy: Clinical Global Impressions-Severity and sustained response (MADRS total score≤12 for at least the last two consecutive double-blind visits). The intent-to-treat population comprised 1133 patients, (placebo=281; vilazodone 20 mg/day=288; vilazodone 40 mg/day=284; citalopram=280). MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day, vilazodone 40 mg/day, and citalopram versus placebo. Sustained response rates were numerically higher, but not significantly different, in all active treatment groups versus placebo. The most common adverse events (≥5% of vilazodone patients, twice the rate of placebo) were diarrhea, nausea, vomiting (vilazodone 40 mg/day only), and insomnia. Improved sexual function (Changes in Sexual Functioning Questionnaire scores) was seen in all groups; between-group differences were not significant. Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD. PMID:25500685

  19. 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

  20. Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial.

    PubMed Central

    Barnes, Thomas Re; Leeson, Verity C; Paton, Carol; Costelloe, Céire; Simon, Judit; Kiss, Noemi; Osborn, David; Killaspy, Helen; Craig, Tom Kj; Lewis, Shôn; Keown, Patrick; Ismail, Shajahan; Crawford, Mike; Baldwin, David; Lewis, Glyn; Geddes, John; Kumar, Manoj; Pathak, Rudresh; Taylor, Simon

    2016-01-01

    BACKGROUND Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. OBJECTIVE To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. DESIGN A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. SETTING Adult psychiatric services, treating people with schizophrenia. PARTICIPANTS Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. INTERVENTIONS Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. MAIN OUTCOME MEASURES The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. RESULTS No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There

  1. Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy Trials for Major Depressive Disorder

    PubMed Central

    Berger, Douglas

    2016-01-01

    While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive-behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, “partially-controlled clinical data” because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials. PMID:26870318

  2. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment)

    PubMed Central

    Nakamura, Tadakatsu; Kubota, Tomoko; Iwakaji, Atsushi; Imada, Masayoshi; Kapás, Margit; Morio, Yasunori

    2016-01-01

    Purpose Cariprazine is a potent dopamine D3-preferring D3/D2 receptor partial agonist in development for the treatment of schizophrenia, bipolar mania, and depression. Pharmacokinetics of cariprazine and the two clinically relevant metabolites (desmethyl- and didesmethyl-cariprazine) was evaluated in a clinical pharmacology study. Methods This was a multicenter, randomized, open-label, parallel-group, fixed-dose (3, 6, or 9 mg/day) study of 28-week duration (≤4-week observation, 12-week open-label treatment, and 12-week follow-up). Once-daily cariprazine was administered to 38 adult patients with schizophrenia. The pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites) was evaluated; efficacy and safety were also assessed. Results Steady state was reached within 1–2 weeks for cariprazine and desmethyl-cariprazine, 4 weeks for didesmethyl-cariprazine, and 3 weeks for total active moieties. Cariprazine and desmethyl-cariprazine levels decreased >90% within 1 week after the last dose, didesmethyl-cariprazine decreased ~50% at 1 week, and total active moieties decreased ~90% within 4 weeks. Terminal half-lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. Effective half-life (calculated from time to steady state) of total active moieties was ~1 week. Incidence of treatment-emergent adverse events was 97.4%; 15.8% of patients discontinued due to adverse events. No abnormal laboratory values or major differences from baseline in extrapyramidal symptoms were observed. Conclusion Cariprazine and its active metabolites reached steady state within 4 weeks, and exposure was dose proportional over the range of 3–9 mg/day. Once-daily cariprazine was generally well tolerated in adult patients with schizophrenia. PMID:26834462

  3. Sono-Electro-Magnetic Therapy for Treating Chronic Pelvic Pain Syndrome in Men: A Randomized, Placebo-Controlled, Double-Blind Trial

    PubMed Central

    Kessler, Thomas M.; Mordasini, Livio; Weisstanner, Christian; Jüni, Peter; da Costa, Bruno R.; Wiest, Roland; Thalmann, George N.

    2014-01-01

    Objective To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. Patients and Methods In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. Results The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was −3.1 points (95% CI −6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks −1.6, 95% CI −2.8 to −0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score −8.3, 95% CI −14.5 to 2.6) than in patients with a longer symptom duration (−0.8, 95% CI −4.6 to 3.1; p for interaction = 0.023). Conclusions Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. Trial Registration ClinicalTrials.gov NCT00688506 PMID:25546177

  4. Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial

    PubMed Central

    Levkovitz, Yechiel; Isserles, Moshe; Padberg, Frank; Lisanby, Sarah H; Bystritsky, Alexander; Xia, Guohua; Tendler, Aron; Daskalakis, Zafiris J; Winston, Jaron L; Dannon, Pinhas; Hafez, Hisham M; Reti, Irving M; Morales, Oscar G; Schlaepfer, Thomas E; Hollander, Eric; Berman, Joshua A; Husain, Mustafa M; Sofer, Uzi; Stein, Ahava; Adler, Shmulik; Deutsch, Lisa; Deutsch, Frederic; Roth, Yiftach; George, Mark S; Zangen, Abraham

    2015-01-01

    Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p+0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p+0.013; remission: 32.6 vs. 14.6%, p+0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment. PMID:25655160

  5. Intranasal adminsitration of oxytocin in postnatal depression: implications for psychodynamic psychotherapy from a randomized double-blind pilot study

    PubMed Central

    Clarici, Andrea; Pellizzoni, Sandra; Guaschino, Secondo; Alberico, Salvatore; Bembich, Stefano; Giuliani, Rosella; Short, Antonia; Guarino, Giuseppina; Panksepp, Jaak

    2015-01-01

    Oxytocin is a neuropeptide that is active in the central nervous system and is generally considered to be involved in prosocial behaviors and feelings. In light of its documented positive effect on maternal behavior, we designed a study to ascertain whether oxytocin exerts any therapeutic effects on depressive symptoms in women affected by maternal postnatal depression. A group of 16 mothers were recruited in a randomized double-blind study: the women agreed to take part in a brief course of psychoanalytic psychotherapy (12 sessions, once a week) while also being administered, during the 12-weeks period, a daily dose of intranasal oxytocin (or a placebo). The pre-treatment evaluation also included a personality assessment of the major primary-process emotional command systems described by Panksepp () and a semi-quantitative assessment by the therapist of the mother’s depressive symptoms and of her personality. No significant effect on depressive symptomatology was found following the administration of oxytocin (as compared to a placebo) during the period of psychotherapy. Nevertheless, a personality trait evaluation of the mothers, conducted in our overall sample group, showed a decrease in the narcissistic trait only within the group who took oxytocin. The depressive (dysphoric) trait was in fact significantly affected by psychotherapy (this effect was only present in the placebo group so it may reflect a positive placebo effect enhancing the favorable influence of psychotherapy on depressive symptoms) but not in the presence of oxytocin. Therefore, the neuropeptide would appear to play some role in the modulation of cerebral functions involved in the self-centered (narcissistic) dimension of the suffering that can occur with postnatal depression. Based on these results, there was support for our hypothesis that what is generally defined as postnatal depression may include disturbances of narcissistic affective balance, and oxytocin supplementation can

  6. Double-blind study of the actively transported levodopa prodrug XP21279 in Parkinson's disease.

    PubMed

    LeWitt, Peter A; Huff, F Jacob; Hauser, Robert A; Chen, Dan; Lissin, Dmitri; Zomorodi, Katie; Cundy, Kenneth C

    2014-01-01

    The objective of this study was to assess the efficacy, safety, and pharmacokinetics of XP21279-carbidopa in patients with Parkinson's disease who experience motor fluctuations compared with immediate-release carbidopa-levodopa tablets. XP21279 is a levodopa prodrug that is actively absorbed by high-capacity nutrient transporters expressed throughout the gastrointestinal tract and then rapidly converted to levodopa by carboxylesterases. XP21279-carbidopa sustained-release bilayer tablets were developed to overcome pharmacokinetic limitations of levodopa by providing more continuous exposure. Patients with motor fluctuations who required carbidopa-levodopa four or five times daily were optimized for 2 weeks each on carbidopa-levodopa four or five times daily and XP21279-carbidopa three times daily in a randomized sequence. Next, they received each optimized treatment for 2 weeks in a double-blind/double-dummy, randomized sequence. The primary outcome measure was change from baseline in daily off time at the end of each double-blind treatment period. All patients at 2 sites underwent pharmacokinetic analyses. Twenty-eight of 35 enrolled patients completed both double-blind treatments. The mean total daily off time was reduced from baseline by a mean (± standard error) of 2.7 hours (± 0.48 hours) for immediate-release carbidopa-levodopa and 3.0 hours (± 0.57 hours) for XP21279-carbidopa (P = 0.49). Among 11 patients who completed pharmacokinetic sampling on each optimized treatment, the percentage deviation from the mean levodopa concentration was lower (P < 0.05) for XP21279-carbidopa than carbidopa-levodopa. Both treatments had a similar incidence of new or worsening dyskinesias. XP21279-carbidopa administered three times daily produced a reduction in off time similar to that of carbidopa-levodopa administered four or five times daily, and the difference was not statistically significant. XP21279-carbidopa significantly reduced variability in levodopa

  7. 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

  8. Adjunctive Treatment with Rhodiola Crenulata in Patients with Chronic Obstructive Pulmonary Disease – A Randomized Placebo Controlled Double Blind Clinical Trial

    PubMed Central

    Chuang, Ming-Lung; Wu, Tzu-Chin; Wang, Yau-Tung; Wang, Yau-Chen; Tsao, Thomas C.-Y.; Wei, James Cheng-Chung; Chen, Chia-Yin; Lin, I-Feng

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a low grade systemic inflammatory disease characterized by dyspnea and exercise intolerance even under standard therapy. Rhodiola crenulata (RC) has been shown to exert anti-inflammatory effects and to enhance exercise endurance, thereby having the potential to treat COPD. In this 12-week, randomized, double-blind, placebo-controlled clinical trial, 57 patients with stable moderate-to-severe COPD aged 70±8.8 years were given RC (250 mg twice/day) (n=38) or a placebo (250 mg twice/day) (n=19) in addition to their standard regimen. There were no significant differences in anthropometrics, quality of life, lung function, six-minute walk and incremental exercise tests between the two groups at enrollment. Over the 12 weeks, RC was well tolerated, significantly reduced triceps skin thickness (Δ=-1 mm, p=.04), change of FEV1 (4.5%, p=.03), and improved workload (Δ=10%, p=.01); although there were no significant differences in these factors between the two groups. However, there were significant between-group differences in tidal volume and ventilation-CO2-output ratio at peak exercise (both p=.05), which were significantly related to peak work rate (both p<.0001). RC tended to protect against acute exacerbation of COPD (p=.1) but not other measurements. RC did not improve the six-minute walk test distance but significantly improved tidal breathing and ventilation efficiency, most likely through improvements in work rate. Further studies with a larger patient population are needed in order to confirm these findings. Trial Registration ClinicalTrials.gov number NCT02242461 PMID:26098419

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

    PubMed Central

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

    2015-01-01

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

  10. 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

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

    PubMed

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

    2015-05-01

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

  12. A CONSORT-Compliant, Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Purified Anthocyanin in Patients With Nonalcoholic Fatty Liver Disease

    PubMed Central

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

    2015-01-01

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

  13. Improvement of erectile function with Prelox: a randomized, double-blind, placebo-controlled, crossover trial.

    PubMed

    Stanislavov, R; Nikolova, V; Rohdewald, P

    2008-01-01

    In a randomly allocated, double-blind, placebo-controlled, crossover design, 50 patients with mild to moderate erectile dysfunction (ED) were treated for 1 month with placebo or a combination of L-arginine aspartate and Pycnogenol (Prelox). Patients reported sexual function from diaries. Testosterone levels and endothelial NO synthase (e-NOS) were monitored along with routine clinical chemistry. Intake of Pycnogenol for 1 month restored erectile function to normal. Intercourse frequency doubled. e-NOS in spermatozoa and testosterone levels in blood increased significantly. Cholesterol levels and blood pressure were lowered. No unwanted effects were reported. Prelox is a promising alternative to treat mild to moderate ED. PMID:17703218

  14. A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

    PubMed Central

    Vischer, T L

    1988-01-01

    The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

  15. [Parallel double-blind comparison of bazalin and desoximetasone 0.25 in neurodermatitis].

    PubMed

    Gratacos, R

    1981-01-01

    In a double-blind study on 22 patients affected by neurodermitis the action of two ointmes was studied. Both possess an activity in controlling the clinical and histological manifestations of the disease. Desoximethasone (red labelled tubes) is very usefull in controlling pruritus and, histologically, the epidermal component of the lesions. Bazalin (yellow labeled tubes containing fluocinolone acetonide 0.025%, leucobitupal 5% an salicylic acid 3%), has a higher antiscaling action a more intense activity on the dermal component of the lesions. PMID:7038354

  16. A double blind trial of a new topical steroid formulation containing desoximetasone against fluocinolonacetonid cream.

    PubMed

    Lundell, E

    1975-01-01

    A randomized double-blind left-right comparative trial was carried out between a new steroid Desoximetason 0,25% (Ibaril) and fluocinolone acetonide 0,025% cream. Evaluation of symptoms on 50 patients suffering from endogenous eczema was recorded after 1, 2, 3 and 4 weeks. There was a significantly better effect of Ibaril compared to Fluocinolone-acetonide as judged by the observer during the 1st, 3rd and 4th week of treatment. After the 2nd week treatment Ibaril showed a better effect, however, a significancy could not be established. PMID:132779

  17. Regular consumption of Fiit-ns, a polyphenol extract from fruit and vegetables frequently consumed within the Mediterranean diet, improves metabolic ageing of obese volunteers: a randomized, double-blind, parallel trial.

    PubMed

    Cases, Julien; Romain, Cindy; Dallas, Constantin; Gerbi, Alain; Cloarec, Maurice

    2015-02-01

    Epidemiological studies suggest that metabolic ageing process of overweight and obese populations is associated with an increased risk of developing non-communicable diseases (NCDs). Inflammation, hyper-glycaemia, dyslipidemia and oxidative stress have been associated with early stages of NCDs development whereas cohort surveys have demonstrated health benefits of dietary polyphenols from various dietary sources to reverse such progress. Obese volunteers were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a polyphenol-rich treatment extracted from fruit and vegetables frequently consumed within the Mediterranean diet. Anthropometric and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and general satisfaction considerably ameliorated. These data suggest that over a 12-week period, the synergistic action of bioactives within the treatment improves metabolic ageing process and quality of life in obese volunteers. PMID:25358490

  18. Efficacy and safety of a dieckol-rich extract (AG-dieckol) of brown algae, Ecklonia cava, in pre-diabetic individuals: a double-blind, randomized, placebo-controlled clinical trial.

    PubMed

    Lee, Seung-Hong; Jeon, You-Jin

    2015-03-01

    The effects of 12 weeks of supplementation with a dieckol-rich extract (AG-dieckol) from brown algae, Ecklonia cava, on glycemic parameters, serum biochemistry, and hematology were investigated in this study. Eighty pre-diabetic male and female adults were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Subjects were randomly allocated into two groups designated as placebo and AG-dieckol (1500 mg per day). Compared with the placebo group, the AG-dieckol group showed a significant decrease in postprandial glucose levels after 12 weeks. The AG-dieckol group also showed a significant decrease in insulin and C-peptide levels after 12 weeks, but there was no significant difference between the AG-dieckol and placebo groups. There were no significant adverse events related to the consumption of AG-dieckol, and biochemical and hematological parameters were maintained within the normal range during the intervention period. In conclusion, these results demonstrate that AG-dieckol supplementation significantly contributes to lowering postprandial hyperglycemia and in reducing insulin resistance. Furthermore, we believe that based on these results the consumption of phlorotannin-rich foods such as marine algae may be useful for the treatment of diabetes. PMID:25608849

  19. Impact of anti-Giardia and anthelminthic treatment on infant growth and intestinal permeability in rural Bangladesh: a randomised double-blind controlled study.

    PubMed

    Goto, Rie; Mascie-Taylor, C G Nicholas; Lunn, Peter G

    2009-05-01

    In order to test the impact of Giardia and geohelminthic infection on infant growth faltering in Bangladesh, a randomised double-blind placebo controlled intervention of 36 weeks' duration was conducted in a rural community located 40 km northwest of Dhaka. Infants aged between 3 and 15 months were randomly assigned to either anti-Giardia and anthelminthic treatment, anti-Giardia treatment only, or a control. Weight and supine length were recorded every 4 weeks. Every 12 weeks intestinal permeability (lactulose/mannitol ratio), haemoglobin, plasma albumin, alpha-1-acid glycoprotein, IgG and Giardia-specific IgM (GSIgM) and eggs of the three common geohelminths and G. intestinalis cysts were determined. Data on 222 fully compliant infants were analysed. No significant differences in intestinal permeability, biochemical or anthropometric variables were found between the intervention groups, although there were associations between improvement in small intestinal mucosal function and better weight-for-age and weight-for-height (length) Z-scores. GSIgM titres indicated high endemicity with rapid re-infection of Giardia among infants; over 95% of infants were positive throughout the study, whereas the stool examination showed very few infants with either geohelminth eggs or Giardia cysts. PMID:18789466

  20. Armodafinil versus Modafinil in Patients of Excessive Sleepiness Associated with Shift Work Sleep Disorder: A Randomized Double Blind Multicentric Clinical Trial

    PubMed Central

    Tembe, D. V.; Dhavale, A.; Desai, H.; Mane, D. N.; Raut, S. K.; Dhingra, G.; Sardesai, U.; Saoji, S.; Rohra, M.; Shinde, V. G.; Padsalge, M.; Paliwal, A.; Abbasi, K.; Devnani, P.; Papinwar, S.; Phadke, S.; Mehta, H.; Bhailume, V.

    2011-01-01

    Aim. To compare the efficacy and safety of armodafinil, the R-enantiomer of modafinil, with modafinil in patients of shift work sleep disorder (SWSD). Material and Methods. This was a 12-week, randomized, comparative, double-blind, multicentric, parallel-group study in 211 patients of SWSD, receiving armodafinil (150 mg) or modafinil (200 mg) one hour prior to the night shift. Outcome Measures. Efficacy was assessed by change in stanford sleepiness score (SSS) by at least 2 grades (responder) and global assessment for efficacy. Safety was assessed by incidence of adverse events, change in laboratory parameters, ECG, and global assessment of tolerability. Results. Both modafinil and armodafinil significantly improved sleepiness mean grades as compared to baseline (P < .0001). Responder rates with armodafinil (72.12%) and modafinil (74.29%) were comparable (P = .76). Adverse event incidences were comparable. Conclusion. Armodafinil was found to be safe and effective in the treatment of SWSD in Indian patients. The study did not demonstrate any difference in efficacy and safety of armodafinil 150 mg and modafinil 200 mg. PMID:21766023

  1. A randomised, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia in Brazil

    PubMed Central

    POMPEO, A C L; ROSENBLATT, C; BERTERO, E; DA ROS, C T; CAIROLI, C E D; DAMIÃO, R; WROCLAWSKI, E R; KOFF, W J; MESQUITA, F; PINHEIRO, G E

    2006-01-01

    Brazilian patients with benign prostatic hyperplasia were randomised in a 12-week, double-blind, double-dummy study to receive doxazosin gastrointestinal therapeutic system (GITS) 4 mg q.i.d. (n = 82) or tamsulosin 0.4 q.i.d. (n = 83). Primary endpoints were the absolute and percentage change from baseline in symptoms measured by International Prostate Symptom Score (IPSS). Secondary endpoints included IPSS, quality-of-life (QOL) question from the IPSS, and questions 6 and 7 of the Sexual Function Abbreviated Questionnaire (SFAQ) at weeks 4 and 12. Doxazosin GITS and tamsulosin improved IPSS with no significant differences between groups at week 12. During weeks 4–8, tamsulosin-treated patients demonstrated a slower improvement (p < 0.001) in IPSS than doxazosin GITS-treated patients. The proportion of satisfied patients was observed earlier with doxazosin GITS (p = 0.006) vs. tamsulosin. At week 12, the proportion of patients with little or no difficulty at ejaculation (Q6 of SFAQ) was higher in the doxazosin GITS group (p = 0.019). Both treatments were well tolerated. PMID:16942589

  2. A randomised, double-blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia.

    PubMed

    Karlsson, I; Godderis, J; Augusto De Mendonça Lima, C; Nygaard, H; Simányi, M; Taal, M; Eglin, M

    2000-04-01

    Depression is the most common psychiatric disorder among the elderly and in old age may interact with emotional and cognitive functioning. Depression in old age has been shown to be associated with degenerative changes in the brain. It is, therefore, important that in this patient population antidepressants with a favourable tolerability profile, such as the selective serotonin reuptake inhibitors (SSRIs), are examined for both antidepressant efficacy and effect on cognitive function and emotional impairment. This randomised, double-blind study compared the efficacy and tolerability of citalopram and mianserin in 336 elderly, depressed patients with or without dementia. Patients received either citalopram 20-40 mg/day or mianserin 30-60 mg/day for 12 weeks. The treatments were equivalent with respect to change in Montgomery-Asberg Depression Rating Scale (MADRS) total score; patients in both treatment groups responded well. Patients with dementia showed a smaller decrease in total MADRS score than patients without dementia. Both treatments were well tolerated with a relatively low incidence of adverse events. Fatigue and somnolence were more frequent with mianserin, while insomnia was more frequent with citalopram. Overall, this study showed that the two treatments were equivalent in efficacy, and that citalopram is an effective, well-tolerated and non-sedative treatment for elderly depressed patients with or without dementia. PMID:10767728

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

    PubMed

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

    2016-06-01

    The objective of this substudy was to examine the effect of desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for desvenlafaxine (-226.6 msec (-316.7, -136.4); P<0.0001) and for placebo (-133.3 msec (-257.2, -9.4); P=0.0354); however, the treatment effect was not significant. No significant differences between groups were observed on composite measures for attention. Treatment of depression with desvenlafaxine 50 mg/day may improve aspects of cognitive functioning, including working memory.Clinical Trial Registry No.: Clinicaltrials.gov identifier: NCT00824291. PMID:27009044

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  7. Dietary Supplementation with a Superoxide Dismutase-Melon Concentrate Reduces Stress, Physical and Mental Fatigue in Healthy People: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Carillon, Julie; Notin, Claire; Schmitt, Karine; Simoneau, Guy; Lacan, Dominique

    2014-01-01

    Background: We aimed to investigate effects of superoxide dismutase (SOD)-melon concentrate supplementation on psychological stress, physical and mental fatigue in healthy people. Methods: A randomized, double-blind, placebo-controlled trial was performed on 61 people divided in two groups: active supplement (n = 32) and placebo (n = 29) for 12 weeks. Volunteers were given one small hard capsule per day. One capsule contained 10 mg of SOD-melon concentrate (140 U of SOD) and starch for the active supplement and starch only for the placebo. Stress and fatigue were evaluated using four psychometric scales: PSS-14; SF-36; Stroop tests and Prevost scale. Results: The supplementation with SOD-melon concentrate significantly decreased perceived stress, compared to placebo. Moreover, quality of life was improved and physical and mental fatigue were reduced with SOD-melon concentrate supplementation. Conclusion: SOD-melon concentrate supplementation appears to be an effective and natural way to reduce stress and fatigue. Trial registration: trial approved by the ethical committee of Poitiers (France), and the ClinicalTrials.gov Identifier is NCT01767922. PMID:24949549

  8. Supplementation of xylitol-containing chewing gum with probiotics: a double blind, randomised pilot study focusing on saliva flow and saliva properties.

    PubMed

    Gueimonde, Laura; Vesterlund, Satu; García-Pola, María J; Gueimonde, Miguel; Söderling, Eva; Salminen, Seppo

    2016-03-01

    The aim of this study was to investigate the impact of daily chewing, for 12 weeks, of 2 different probiotic gums compared with placebo on saliva flow rate, saliva IgA levels and saliva pH. The intervention study included 54 adult volunteers with hyposalivation in a double-blind, randomised and placebo-controlled design with three parallel groups. Volunteers were randomly assigned to 3 different groups: subjects in group A (n = 19) were given placebo chewing gum, group B (n = 17) received Bifidobacterium animalis ssp. lactis Bb12 (ATCC 27536) and group C (n = 18) received Lactobacillus rhamnosus LGG (ATCC 53103), Bifidobacterium longum 46 (DSM 14583) and Bifidobacterium longum 2C (DSM 14579) gums, during 3 months. Two volunteers from group B left the study for personal reasons leaving 19, 15 and 18 volunteers, respectively, for analyses. Clinical examinations, personal interviews, sialometries and saliva sampling were conducted at baseline and after 1, 2, 3 and 4 months. No statistically significant differences were found between probiotic and placebo groups for any of the parameters analysed. No side effects of probiotic or placebo chewing gums were observed. Chewing gum, with and without probiotics, had a positive impact on salivary flow rate and saliva pH and IgA levels. PMID:26913493

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  11. A Double-Blind Placebo-Controlled Trial of Maca Root as Treatment for Antidepressant-Induced Sexual Dysfunction in Women

    PubMed Central

    Dording, Christina M.; Schettler, Pamela J.; Dalton, Elizabeth D.; Parkin, Susannah R.; Walker, Rosemary S. W.; Fehling, Kara B.; Fava, Maurizio

    2015-01-01

    Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126. PMID:25954318

  12. A double-blind placebo-controlled trial of maca root as treatment for antidepressant-induced sexual dysfunction in women.

    PubMed

    Dording, Christina M; Schettler, Pamela J; Dalton, Elizabeth D; Parkin, Susannah R; Walker, Rosemary S W; Fehling, Kara B; Fava, Maurizio; Mischoulon, David

    2015-01-01

    Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depression remitted. Endpoints were improvement in sexual functioning as per the Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ). Results. 45 of 57 consented females were randomized, and 42 (30 premenopausal and 12 postmenopausal women) were eligible for a modified intent-to-treat analysis based on having had at least one postmedication visit. Remission rates by the end of treatment were higher for the maca than the placebo group, based on attainment of an ASEX total score ≤ 10 (9.5% for maca versus 4.8% for placebo), attaining an MGH-SFQ score ≤ 12 (30.0% for maca versus 20.0% for placebo) and reaching an MGH-SFQ score ≤ 8 (9.5% for maca versus 5.0% for placebo). Higher remission rates for the maca versus placebo group were associated with postmenopausal status. Maca was well tolerated. Conclusion. Maca root may alleviate SSRI-induced sexual dysfunction in postmenopausal women. This trial is registered with NCT00568126. PMID:25954318

  13. The Effect of Omega-3 Fatty Acids in Patients With Active Rheumatoid Arthritis Receiving DMARDs Therapy: Double-Blind Randomized Controlled Trial

    PubMed Central

    Rajaei, Elham; Mowla, Karim; Ghorbani, Ali; Bahadoram, Sara; Bahadoram, Mohammad; Dargahi-Malamir, Mehrdad

    2016-01-01

    Background: Rheumatoid arthritis is a symmetric peripheral polyarthritis of unknown etiology that, untreated or if unresponsive the therapy, typically leads to deformity and destruction of joints due to erosion of cartilage and bone. Omega-3 fatty acids have been shown to reduce morning stiffness, the number of tender joints and swollen joints in patients with rheumatoid arthritis. This study is designed for evaluation of omega-3 effects on disease activity and remission of rheumatoid arthritis in DMARDs treated patients and on weight changes and reduction of analgesic drugs consumption versus placebo. Methods: Sixty patients with active rheumatoid arthritis (49 female and 11 male) underwent rheumatologist examination and disease activity score were calculated. Then patients were enrolled in this 12 week, double blind, randomized, placebo- controlled study. The patients in both groups continued their pre study standard treatment. The patients were visited every 4 weeks, 4 times and data were recorded. Results: Significant improvement in the patient’s global evaluation and in the physician’s assessment of disease was observed in those taking omega-3. The proportions of patients who improved and of those who were able to reduce their concomitant analgesic medication were significantly greater with omega-3 consumption. There were no weight changes. Conclusion: Daily supplementation with omega-3 results has significant clinical benefit and may reduce the need for concomitant analgesic consumption without weight changes. PMID:26925896

  14. Hydroxyurea: a radiation potentiator in carcinoma of the uterine cervix. A randomized double-blind study

    SciTech Connect

    Piver, M.S.; Barlow, J.J.; Vongtama, V.; Blumenson, L.

    1983-12-01

    From June, 1972, to December, 1976, 40 patients with FIGO (International Federation of Gynaecology and Obstetrics) Stage IIB carcinoma of the uterine cervix were entered into a prospective, double-blind, randomized study to evaluate the possible radiation-potentiating properties (i.e., improved survival) of the S-phase cell cycle-specific inhibitor of DNA synthesis, hydroxyurea. All patients were documented to be without aortic lymph node metastasis by pretherapy staging para-aortic lymphadenectomy. All 40 patients were followed up for longer than 5 years (5.2 to 9.2 years) or until death. The double-blind code was not broken until all patients had been followed up for a minimum of 2 to 5 years. Leukopenia (white blood cell count less than 2,500 mm3) was significantly increased in the patients given hydroxyurea as compared to those given placebo (P less than 0.0001). There was no statistically significant difference relative to anemia, thrombocytopenia, radiation-induced skin reaction, and radiation-induced intestinal reaction between the patients given placebo or those given hydroxyurea. Life-table survival for the patients given hydroxyurea was 94% as compared to 53% for the patients given placebo (P . 0.006). Only one (5%) patient given hydroxyurea died of cervical cancer. Of the other patients who died in the group given hydroxyurea, all were confirmed by postmortem examination to have been without recurrent cervical cancer. In contrast, 45% (nine) of the patients given placebo died of cervical cancer.

  15. Monosodium L-glutamate: a double-blind study and review.

    PubMed

    Tarasoff, L; Kelly, M F

    1993-12-01

    71 healthy subjects were treated with placebos and monosodium L-glutamate (MSG) doses of 1.5, 3.0 and 3.15 g/person, which represented a body mass-adjusted dose range of 0.015-0.07 g/kg body weight before a standardized breakfast over 5 days. The study used a rigorous randomized double-blind crossover design that controlled for subjects who had MSG after-tastes. Capsules and specially formulated drinks were used as vehicles for placebo and MSG treatments. Subjects mostly had no responses to placebo (86%) and MSG (85%) treatments. Sensations, previously attributed to MSG, did not occur at a significantly higher rate than did those elicited by placebo treatment. A significant (P < 0.05) negative correlation between MSG dose and after-effects was found. The profound effect of food in negating the effects of large MSG doses was demonstrated. The common practice of extrapolating food-free experimental results to 'in use' situations was called into question. An exhaustive review of previous methodologies identified the strong taste of MSG as the factor invalidating most 'blind' and 'double-blind' claims by previous researchers. The present study led to the conclusion that 'Chinese Restaurant Syndrome' is an anecdote applied to a variety of postprandial illnesses; rigorous and realistic scientific evidence linking the syndrome to MSG could not be found. PMID:8282275

  16. Postoperative Neurocognitive Dysfunction in Patients Undergoing Cardiac Surgery after Remote Ischemic Preconditioning: A Double-Blind Randomized Controlled Pilot Study

    PubMed Central

    Meybohm, Patrick; Renner, Jochen; Broch, Ole; Caliebe, Dorothee; Albrecht, Martin; Cremer, Jochen; Haake, Nils; Scholz, Jens; Zacharowski, Kai; Bein, Berthold

    2013-01-01

    Background Remote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery. Methods We conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion). Results According to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5–7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19–1.94) µg/L vs. 0.48 (0.07–1.84) µg/L] and 24 hours after surgery [0.36 (0.14–1.89) µg/L vs. 0.26 (0.07–0.90) µg/L]. Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed. Trial Registration ClinicalTrials.gov NCT00877305 PMID:23741380

  17. Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

    PubMed Central

    Ställberg, Björn; Selroos, Olof; Vogelmeier, Claus; Andersson, Eva; Ekström, Tommy; Larsson, Kjell

    2009-01-01

    Background Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation. Methods This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV1 30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home. A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV1 45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV1 was the primary efficacy variable. Non-inferiority was predefined. Results Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV1-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified. Conclusion High dose budesonide/formoterol was as

  18. Effects of Pitavastatin on Lipid Profiles in HIV-Infected Patients with Dyslipidemia and Receiving Atazanavir/Ritonavir: A Randomized, Double-Blind, Crossover Study

    PubMed Central

    Wongprikorn, Asita; Sukasem, Chonlaphat; Puangpetch, Apichaya; Numthavej, Pawin; Thakkinstian, Ammarin; Kiertiburanakul, Sasisopin

    2016-01-01

    Background Dyslipidemia as a risk factor of cardiovascular disease is common especially in HIV-infected patients who are using protease inhibitors (PIs) including atazanavir. Pitavastatin has less drug-drug interactions and demonstrable efficacy in decreasing lipid levels in non HIV-infected individuals. Materials and Methods This study was a randomized, double-blind, crossover study comparing the safety and efficacy of pitavastatin vs placebo in HIV-infected patients with dyslipidemia and receiving atazanavir/ritonavir (ATV/r). Patients were randomized to receive either placebo or pitavastatin for 12 weeks. The follow-up visits were every 4 weeks until the end of the study. Results A total of 12 HIV-infected patients were enrolled to each study group. Of all, 14 (58%) patients were men and mean (standard deviation, SD) age was 48.1 (1.8) years. At 12 weeks of treatment with pitavastatin compared to placebo; mean [95% confidence interval (CI)] total cholesterol (TC) was 207 (187.3, 226.8) mg/dL vs 246.3 (226.5, 266) mg/dL (p <0.001); mean (95% CI) triglyceride (TG) was 351.3 (193.2, 509.4) mg/dL vs 279.1 (121, 437.2) mg/dL (p = 0.269); mean (95% CI) high density lipoprotein (HDL) was 45.3 (40.4, 50.2) mg/dL vs 44.2 (39.3, 49.1) mg/dL (p = 0.354); and mean (95% CI) low density lipoprotein (LDL) was 113.2 (100.4, 126) mg/dL vs 145.6 (132.8, 158.4) mg/dL (p <0.001). Mean liver enzyme and median creatine phosphokinase levels were not statistically significant between patients receiving placebo and pitavastatin. Conclusions Pitavastatin decreases TC and LDL level at 12 weeks significantly and shows indifferent in hepatotoxicity and creatine phosphokinase levels compared to those of placebo. Thus, pitavastatin can be a good option of lipid-lowering agent in HIV-infected patients who are receiving ATV/r. Trial Registration ClinicalTrials.gov NCT02442700 PMID:27304841

  19. A multicenter, randomized, double-blind trial of a new porcine surfactant in premature infants with respiratory distress syndrome

    PubMed Central

    Rebello, Celso Moura; Precioso, Alexander Roberto; Mascaretti, Renata Suman

    2014-01-01

    Objective To compare the efficacy and safety of a new porcine-derived pulmonary surfactant developed by Instituto Butantan with those of animal-derived surfactants commercially available in Brazil, regarding neonatal mortality and the major complications of prematurity in preterm newborns with birth weight up to 1500g and diagnosed with respiratory distress syndrome. Methods Neonates diagnosed with respiratory distress syndrome were randomized to receive either Butantan surfactant (Butantan group) or one of the following surfactants: Survanta® or Curosurf®. Newborns receiving Survanta® or Curosurf® comprised the control group. The main outcome measures were mortality rates at 72 hours and at 28 days of life; the typical complications of prematurity as evaluated on the 28th day of life were defined as secundary outcomes. Results No differences were observed between the Butantan (n=154) and control (n=173) groups in relation to birth weight, gestational age, sex, and prenatal use of corticosteroids, or in mortality rates both at 72 hours (14.19% versus 14.12%; p=0.98) and at 28 days (39.86% versus 33.33%; p=0.24) of life. Higher 1- and 5-minute Apgar scores were observed among control group newborns. No differences were observed as regards the secondary outcomes, except for greater need for supplemental oxygen and a higher incidence of interstitial pulmonary emphysema in the Butantan group. Conclusion The mortality rates at 72 hours and 28 days of life and the incidence of major complications of prematurity were comparable to those found with the animal-derived surfactants commercially available in Brazil, showing the efficacy and safety of the new surfactant in the treatment of respiratory distress syndrome in newborns. PMID:25628188

  20. Paroxetine Treatment in Children and Adolescents with Major Depressive Disorder: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Wagner, Karen Dineen; Kutcher, Stan; Krulewicz, Stan; Fong, Regan; Carpenter, David J.; Lipschitz, Alan; Machin, Andrea; Wilkinson, Christel

    2006-01-01

    Objective: To assess the efficacy and tolerability of paroxetine in pediatric major depressive disorder. Method: Subjects 7 to 17 years old with major depressive disorder received paroxetine (10-50 mg/day) or placebo for 8 weeks from 2000 to 2001. The primary efficacy measure was change from baseline in the Children's Depression Rating…

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

    PubMed Central

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

    2016-01-01

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

  2. Ionization with diclofenac sodium in rheumatic disorders: a double-blind placebo-controlled trial.

    PubMed

    Vecchini, L; Grossi, E

    1984-01-01

    A double-blind randomized study was performed to compare ionization with diclofenac sodium (150 mg) and ionization with saline solution in two groups of patients with scapulo-humeral periarthritis or elbow epicondylitis. The subjects of both groups were treated with 20 ionization sessions each lasting 30 minutes during a 1-month period. There was a significantly greater improvement in pain at rest, pain on pressure, pain on movement and joint swelling in the eleven patients treated with diclofenac compared with the thirteen placebo-treated patients, but no significant differences between the two treatments as regards functional impairment. However, placebo treatment produced a slight but significant improvement in pain on pressure, pain on movement and functional impairment. Further studies are needed to assess the relative role of the current and of autosuggestion in saline ionization response since both have well-known therapeutic effects on chronic rheumatic pain. PMID:6394405

  3. Anabolic steroids in athelics: crossover double-blind trial on weightlifters.

    PubMed Central

    Freed, D L; Banks, A J; Longson, D; Burley, D M

    1975-01-01

    Thirteen experienced male weightlifters taking high-protein diets and regular exercise took part in a double-blind crossover trial of methandienone 10 or 25 mg/day to seeif the drug improved athletic performance. Their improvemments were significantly greater on methandienone than on placebo; their body weights rose (though this seemed to be associated with water retention); and systolic blood pressure rose significantly. Methandienone caused many side effects, and three men had to withdraw because of them. All side effects disappeared after the drug was stopped. Anabolic steroids are effective only when given combination with exercise and high-protein diet.We deprecate their use in athletics but can suggest no way of stopping it. PMID:125133

  4. A randomized, double-blind, placebo-controlled trial of pseudoephedrine in coryza.

    PubMed

    Latte, Jenny; Taverner, David; Slobodian, Peter; Shakib, Sepehr

    2004-07-01

    1. The aim of the present study was to assess the efficacy of pseudoephedrine in coryza. 2. In a double-blind, randomized, placebo-controlled design, 48 adults with acute coryza received a single oral dose of 60 mg pseudoephedrine (Sudafed; Pfizer Consumer HealthCare Group, Caringbah, NSW, Australia) or matching placebo. Before and after dosing, nasal airway resistance (NAR), nasal volume, the minimum intranasal cross-sectional area (MCA) and the symptom of nasal congestion were measured. 3. Pseudoephedrine produced a significant decrease in NAR (P = 0.005; 95% confidence interval (CI) 0.073, 0.383). Nasal volume increased, but this did not reach significance (P = 0.07; 95% CI -0.842, 0.034). There was no change in MCA and symptoms. 4. In conclusion, pseudoephedrine has a moderate effect in decreasing objective measures of nasal congestion in coryza. PMID:15236629

  5. Treatment of chronic idiopathic urticaria with levamisole: a multicentre, randomized, double-blind, controlled trial.

    PubMed

    Zhang, H; Shan, C; Hua, Z; Zhao, P; Zhang, H

    2009-01-01

    The objective of this study was to evaluate the efficacy of treating chronic idiopathic urticaria (CIU) with levamisole in combination with levocetirizine. This was a multicentre, randomized, double-blind, controlled trial that included 132 patients with active CIU who were treated for 6 weeks with either levocetirizine alone (control group; n = 65) or levamisole plus levocetirizine (treatment group; n = 67). Response to therapy was evaluated by measuring the efficacy rate. After 2 weeks of treatment, there was no significant difference in the efficacy rate between the treatment and control groups (54.84% and 42.37%, respectively). After 6 weeks of treatment, a statistically significant difference in the efficacy rate was observed between the groups (76.27% and 54.39% for the treatment and control groups, respectively). This study demonstrated that a combination of levamisole plus levocetirizine is more effective than levocetirizine alone and potentially provides a new, promising approach to the treatment of CIU. PMID:19761700

  6. Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study.

    PubMed

    Asgary, S; Naderi, G H; Sadeghi, M; Kelishadi, R; Amiri, M

    2004-01-01

    The aim of the present study was to investigate the potential antihypertensive effects of extracts of the flavonoid-rich Iranian flower, Crataegus curvisepala Lind., a member of the Rosaceae family. The hydroalcoholic extract of the leaves and flowers were studied in a double-blind, placebo-controlled clinical trial to determine its effects. A total of 92 men and women with primary mild hypertension, aged 40-60 years, were selected and divided randomly into two groups, receiving either hydroalcoholic extract of C. curvisepala Lind. or placebo three times daily for more than 4 months. Blood pressure (BP) was measured each month. Statistical analysis was carried out using Student's t-test. The results obtained showed a significant decrease in both systolic and diastolic BP after 3 months (p < 0.05). C. curvisepala has a time-dependent antihypertensive effect. PMID:15700749

  7. Randomised, double blind, crossover challenge study of allergenicity of peanut oils in subjects allergic to peanuts.

    PubMed Central

    Hourihane, J. O.; Bedwani, S. J.; Dean, T. P.; Warner, J. O.

    1997-01-01

    OBJECTIVE: To determine the in vivo allergenicity of two grades of peanut oil for a large group of subjects with proved allergy to peanuts. DESIGN: Double blind, crossover food challenge with crude peanut oil and refined peanut oil. SETTING: Dedicated clinical investigation unit in a university hospital. SUBJECTS: 60 subjects allergic to peanuts; allergy was confirmed by challenge tests. OUTCOME MEASURES: Allergic reaction to the tested peanut oils. RESULTS: None of the 60 subjects reacted to the refined oil; six (10%) reacted to the crude oil. Supervised peanut challenge caused considerably less severe reactions than subjects had reported previously. CONCLUSIONS: Crude peanut oil caused allergic reactions in 10% of allergic subjects studied and should continue to be avoided. Refined peanut oil did not pose a risk to any of the subjects. It would be reasonable to recommend a change in labelling to distinguish refined from crude peanut oil. PMID:9133891

  8. Terbutaline depot tablets in childhood asthma. A double-blind controlled study.

    PubMed

    Foged, N; Høst, A; Ljungholm, K

    1985-10-01

    Thirty children 8-13 years old, with perennial asthma and with a reversibility of greater than or equal to 20% in lung function (FEV1) were given a sustained-release preparation of terbutaline sulphate 5 mg twice a day and ordinary tablets 2.5 mg three times a day; each treatment lasted 1 week. The design of the study was double-blind, cross-over, with a randomized allocation of the drugs. Both drugs improved the lung function significantly. The children had significantly less coughing during the night when they took depot tablets than when they took ordinary tablets. The side effects were few with both treatments. Most of the patients preferred the depot tablets. PMID:3907394

  9. Effects of Atorvastatin on Negative Sign in Chronic Schizophrenia: a Double Blind Clinical Trial

    PubMed Central

    Sayyah, Mehdi; Boostani, Hatam; Ashrafpoori, Mitra; Pakseresht, Siroos

    2015-01-01

    The aim of this study was to evaluate the effects of Atorvastatin on negative symptoms in patients with chronic schizophrenia. The study was a prospective, double-blind, 6-week trial. Forty patients participated in the study; 19 patients were assigned to the Atorvastatin group as well as 21 patients to the placebo group. For assessing negative signs, we used Scale for the Assessment of Negative Symptoms (SANS) in weeks 1st, 3nd, 4th, and 6th. Moreover, patients were randomly assigned to treatment groups with Risperidone (6 mg/day) plus 20 mg Atorvastatin or with Risperidone (6 mg/day) plus placebo. Mean scores of Scale for the Assessment of Negative Symptoms (SANS) decreased during the treatment but there was no significant difference between the mean scores of two groups. The result of this trial suggested that Atorvastatin can be effective in reducing negative sign in schizophrenia although further studies seem to be needed. PMID:26664396

  10. Hydroxychloroquine sulphate in the treatment of rheumatoid arthritis: a double blind comparison of two dose regimens.

    PubMed Central

    Pavelka, K; Sen, K P; Pelísková, Z; Vácha, J; Trnavský, K

    1989-01-01

    A controlled, double blind, parallel group, long term study of hydroxychloroquine sulphate in the treatment of rheumatoid arthritis, comparing daily doses of 200 mg and 400 mg, is described. The trial involved 54 patients with moderate disease activity who had not previously received antimalarial drugs. Forty three patients completed the one year treatment. The groups receiving different doses were homogeneous and did not differ in any of the 25 monitored indicators. Both dose regimens were effective, and a significant reduction of disease activity was observed after one year's treatment. Of the nine laboratory and 11 clinical indices of efficacy monitored, no statistically significant differences were reported, but in the group of patients treated with the 400 mg daily dose the number of side effects was three times greater. As there have been no reports of retinopathy with hydroxychloroquine at daily doses of 200 mg the effectiveness of this dose is of practical importance. PMID:2673079

  11. Double-blind comparison of survival analysis models using a bespoke web system.

    PubMed

    Taktak, A F G; Setzkorn, C; Damato, B E

    2006-01-01

    The aim of this study was to carry out a comparison of different linear and non-linear models from different centres on a common dataset in a double-blind manner to eliminate bias. The dataset was shared over the Internet using a secure bespoke environment called geoconda. Models evaluated included: (1) Cox model, (2) Log Normal model, (3) Partial Logistic Spline, (4) Partial Logistic Artificial Neural Network and (5) Radial Basis Function Networks. Graphical analysis of the various models with the Kaplan-Meier values were carried out in 3 survival groups in the test set classified according to the TNM staging system. The discrimination value for each model was determined using the area under the ROC curve. Results showed that the Cox model tended towards optimism whereas the partial logistic Neural Networks showed slight pessimism. PMID:17945716

  12. A double-blind placebo-controlled study of Org 3770 in depressed outpatients.

    PubMed

    Claghorn, J L; Lesem, M D

    1995-06-01

    90 patients between 18 and 65 years, with a DSM-III diagnosis of moderate or severe major depressive episode, were randomized to 6 weeks of treatment with Org 3770 or placebo in a double-blind trial. On main efficacy parameters, the 17-item HAMD, MADRS and CGI, Org 3770 was significantly superior to placebo (P < or = 0.05) in weeks 1-4 and at endpoint and recommended as continuation treatment to significantly more patients. The tolerability of Org 3770 was good: the only significant differences as compared with placebo were in the incidences of somnolence and increased appetite. The results show that Org 3770 is an effective and well-tolerated drug for the treatment of major depressive disorder. PMID:7560544

  13. Double-blind evaluation of two commercial hypoallergenic diets in cats with adverse food reactions.

    PubMed

    Leistra, M; Willemse, T

    2002-12-01

    The aim of this study was to evaluate two commercially available selected-protein-source diets as maintenance diets in cats with dermatological manifestations of adverse food reactions. Twenty cats with a confirmed adverse food reaction were tested in a double-blind manner. An adverse food reaction was diagnosed when, after recovery with a home-cooked elimination diet, the signs relapsed after a challenge with their previous dietary components, and re-disappeared on a second elimination diet period. Hereafter the cats were blind and randomly challenged with two commercial hypoallergenic diets. Relapse of the clinical signs was seen in eight cats (40%) on a lamb and rice diet and in 13 cats (65%) on a chicken and rice diet (P>0.05). Neither one of the commercial diets was as effective in controlling the skin problems as the home-cooked elimination diet. The study confirms that commercial hypoallergenic diets are adequate for maintenance. PMID:12468310

  14. Flunarizine-pizotifen single-dose double-blind cross-over trial in migraine prophylaxis.

    PubMed

    Cerbo, R; Casacchia, M; Formisano, R; Feliciani, M; Cusimano, G; Buzzi, M G; Agnoli, A

    1986-03-01

    The results of a double-blind cross-over clinical trial involving 27 patients with classical or common migraine are described to compare the prophylactic effect of the calcium entry blocker flunarizine with that of pizotifen. Duration of the treatment was two months, with an evening single-dose administration of both drugs. For most parameters, there was no definite difference between flunarizine and pizotifen in migraine prophylaxis. It has been demonstrated previously that pizotifen is an effective drug in migraine prophylaxis, and these results suggest that flunarizine is effective, too. Weight gain as a side effect was less frequent and less severe with flunarizine than with pizotifen; other side effects showed the same incidence with both drugs. PMID:3516406

  15. Etizolam versus placebo in the treatment of panic disorder with agoraphobia: a double-blind study.

    PubMed

    Savoldi, F; Somenzini, G; Ecari, U

    1990-01-01

    Thirty out-patients suffering from panic disorders associated with agoraphobia were enrolled in a double-blind, controlled trial to compare the effectiveness and tolerability of etizolam and placebo. After a 1-week washout period on placebo, patients were allocated at random to receive twice daily doses of either 0.5 mg etizolam or placebo over a period of 4 weeks. Assessments, made at baseline and after 2 and 4 weeks of treatment, used the Hamilton Rating Scales for Anxiety and for Depression, the Covi Anxiety Scale, and determination of the weekly panic crises frequency. The results showed that etizolam produced significant improvements in chronic anxiety, phobic ideas, associated depressive symptoms and episodic anxiety, and was significantly more effective than placebo. Etizolam treatment was generally well tolerated and was not significantly different from placebo in this respect. PMID:2272192

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

    PubMed

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

    2002-04-01

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

  17. The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study).

    PubMed

    Itil, T M; Michael, S T; Shapiro, D M; Itil, K Z

    1984-06-01

    Based on computer EEG (CEEG) profiles, in high doses, antidepressant properties of mesterolone, a synthetic androgen, were predicted. In a double-blind placebo controlled study, the clinical effects of 300-450 mg daily mesterolone were investigated in 52 relatively young (age range 26-53 years, mean 42.7 years) male depressed outpatients. During 6 weeks of mesterolone treatment, there was a significant improvement of depressive symptomatology. However, since an improvement was also established during the placebo treatment, no statistically appreciable difference in the therapeutic effects of mesterolone was established compared to placebo. Mesterolone treatment significantly decreased both plasma testosterone and protein bound testosterone levels. Patients with high testosterone levels prior to treatment seem to have had more benefit from mesterolone treatment than patients with low testosterone levels. The degree of improvement weakly correlated to the decrease of testosterone levels during mesterolone treatment. PMID:6431212

  18. Prospective randomized double-blind comparison of nephrotoxicity and auditory toxicity of tobramycin and netilmicin.

    PubMed Central

    Gatell, J M; SanMiguel, J G; Araujo, V; Zamora, L; Maña, J; Ferrer, M; Bonet, M; Bohe, M; Jimenez de Anta, M T

    1984-01-01

    Netilmicin or tobramycin was administered to 197 patients in a prospective randomized double-blind trial. Of these patients, 140 recipients of nine or more doses of netilmicin or tobramycin could be evaluated for nephrotoxicity. Fifty-five patients were able to cooperate in the administration of serial audiograms. Nephrotoxicity of similar severity developed in 7 of 73 (9.6%) recipients of tobramycin and in 7 of 67 (10.4%) recipients of netilmicin (P greater than 0.05). Mild or slight auditory toxicity developed in 5 of 28 (17.8%) recipients of tobramycin and in 2 of 27 (7.4%) recipients of netilmicin (P greater than 0.05). PMID:6393868

  19. Laser acupuncture for adolescent smokers--a randomized double-blind controlled trial.

    PubMed

    Yiming, C; Changxin, Z; Ung, W S; Lei, Z; Kean, L S

    2000-01-01

    A double blind, randomized, placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers. Three hundred and thirty adolescent smokers at the Smoking Cessation Clinic of Child Guidance Clinic, Institute of Health, Singapore, were randomly assigned in equal numbers to laser acupuncture treatment and sham acupuncture (control) groups. The proportions of patients with complete smoking cessation after completing treatment for four weeks were 21.9% in the treatment group and 21.4% in the control group. At three months post-treatment, the rates for complete cessation were 24.8% and 26.2%, respectively. Thus, there was no significant difference in the rates of smoking cessation in the treatment and control groups. PMID:11154059

  20. Double-blind clinical trial of topical steroids in anterior uveitis.

    PubMed Central

    Dunne, J A; Travers, J P

    1979-01-01

    We present the results of a double-blind trial comparing the efficacy of betamethasone phosphate 0.1%, clobetasone butyrate 0.1%, and placebo in the treatment of acute unilateral nongranulomatous uveitis. The 2 steroids were equally comparable in improvement of the patients' symptoms, though betamethasone phosphate was significantly more effective than clobetasone butyrate in improving the ocular signs of uveitis. However, clobetasone butyrate had significantly less effect on raising intraocular pressure in known steroid responders and ocular hypertensives than did dexamethasone. The use of a bolometer as an objective measure in uveitis was significant only in the more severe cases of uveitis. In comparing the placebo group of patients with those on topical steroids, the former group, though improving, appeared to lag behind by approximately one week. Four cases on placebo, however, had to be withdrawn because of worsening of the condition. Mild cases of anterior uveitis would probably resolve without using topical steroids. PMID:389282

  1. Statistical examination of laser therapy effects in controlled double-blind clinical trial

    NASA Astrophysics Data System (ADS)

    Boerner, Ewa; Podbielska, Halina

    2001-10-01

    For the evaluation of the therapy effects the double-blind clinical trial followed by statistical analysis was performed. After statistical calculations it was stated that laser therapy with IR radiation has a significant influence on the decrease of the level of pain in the examined group of patients suffering from various locomotive diseases. The level of pain of patients undergoing laser therapy was statistically lower than the level of pain of patients undergoing placebo therapy. It means that laser therapy had statistically significant influence on the decrease of the level of pain. The same tests were performed for evaluation of movement range. Although placebo therapy contributes to the increase of the range of movement, the statistically significant influence was stated in case of the therapeutic group treated by laser.

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

    PubMed

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

    2014-01-01

    The double blind placebo controlled food challenge (DBPCFC) is the gold standard for diagnosing cow's milk allergy (CMA). However, false-negative DBPCFC have been reported. We present 2 cases with a false negative DBPCFC in exclusively breastfed infants suspected of CMA. These cases highlight the occurrence of severe allergic reactions of infants who were exclusively breastfed. Several reported causes of a false negative DBPCFC will be discussed. However, there is currently no clear understanding of the cause of a false negative DBPCFC. This paper highlights that a negative outcome of a DBFCFC must be interpreted with caution, because a severe allergic reaction might occur upon re-introduction of cow's milk. Therefore, an additional open food challenge under medical supervision is recommended in exclusively breastfed infants with a negative DBPCFC. PMID:24702875

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

    PubMed Central

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

    2002-01-01

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

  4. Double-blind placebo-controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

    PubMed Central

    Ling, Walter; Shoptaw, Steven; Hillhouse, Maureen; Bholat, Michelle A.; Charuvastra, Charles; Heinzerling, Keith; Chim, David; Annon, Jeffrey; Dowling, Patrick T.; Doraimani, Geetha

    2014-01-01

    Aims To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence. Design A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Setting Three substance abuse treatment clinics: two in-patient, one out-patient. Participants Treatment-seeking, methamphetamine-dependent adults (n = 120). Measurements Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. Findings No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. Conclusions The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving. PMID:22082089

  5. Temporary sympathectomy in chronic refractory angina: a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Denby, Christine; Eleuteri, Antonio; Tsang, Hoo kee; Leach, Austin; Hammond, Clare; Bridson, John D; Fisher, Michael; Elt, Matthew; Laflin, Robert; Fisher, Anthony C

    2015-01-01

    Background: Temporary sympathectomy by injection of bupivacaine at the site of the left stellate ganglion is used in the management of refractory angina at several UK centres. Although patients frequently report significant reduction in symptoms, efficacy has not been established by double-blind, randomised placebo-controlled trial (RCT). Objective: To investigate the efficacy of the procedure for the first time by a double-blind RCT. Methods: Consecutive patients referred to the authors’ National Health Service (NHS) angina centre who were candidates for temporary sympathectomy were invited to participate in a trial. A total of 65 patients were randomised to receive either bupivacaine or saline injections. Identical syringes were prepared remotely, blinding patients and staff from randomisation. Cardiac autonomic function was measured 3 hours pre- and post-injection using new heart rate variability (HRV) analyses. Angina episodes were recorded contemporaneously by patients in study diaries in the 7-day periods pre- and post-injection. Results: In 51 patients suitable for analysis, no significant differences between the active and placebo groups were found in patient-recorded frequency or intensity of angina episodes pre- and post-injection. However, across both groups combined, a significant difference was found in the frequency of angina episodes pre- and post-injection. Conclusion: The reduction in frequency of angina episodes produced by this procedure may not be due to drug pharmacology. It may be a placebo response or due to the mechanical effects of the injection of fluid. There is a need for further work using a larger patient cohort considering both mechanical and psychological factors. PMID:26516570

  6. Safety and efficacy of rivastigmine in children with Down syndrome: A double blind placebo controlled trial.

    PubMed

    Spiridigliozzi, Gail A; Hart, Sarah J; Heller, James H; Schneider, Heather E; Baker, Jane Ann; Weadon, Cathleen; Capone, George T; Kishnani, Priya S

    2016-06-01

    Individuals with Down syndrome (DS) have decreased cholinergic function and an uneven profile of cognitive abilities, with more pronounced deficits in learning, memory, and expressive language. Cholinesterase inhibitors may improve cognitive function in adults and adolescents with DS, but studies in children with DS have been limited. This study aimed to: (i) investigate the safety and efficacy of rivastigmine treatment; (ii) build upon our open-label studies in children with DS in a double-blind, placebo-controlled clinical trial; and (iii) investigate specific cognitive domains that may respond to rivastigmine treatment. We conducted a 20-week double-blind, placebo-controlled trial to investigate the safety and efficacy of rivastigmine in 22 children and adolescents with DS aged 10-17 years. Safety measures included reports of adverse events, laboratory parameters, and electrocardiograms. Efficacy measures included parental assessments of adaptive behavior and executive function, and direct measures of language and memory. No group differences were found on safety measures and 22 of 24 participants that passed study screening completed the study. The results did not demonstrate evidence for significant improvement in aspects of cognition, language, or overall function in the children receiving rivastigmine. Our results suggest that rivastigmine is safe and well-tolerated for children and adolescents with DS, but may not be effective for improving performance on the selected measures in this study. However, larger samples and/or alternate measures could possibly reveal improvements in cognitive function with rivastigmine treatment. Further research is needed to define a battery of cognitive measures that is sensitive to treatment effects in DS. © 2016 Wiley Periodicals, Inc. PMID:27061338

  7. Rizatriptan in migraineurs with unilateral cranial autonomic symptoms: a double-blind trial.

    PubMed

    Barbanti, Piero; Fofi, Luisa; Dall'Armi, Valentina; Aurilia, Cinzia; Egeo, Gabriella; Vanacore, Nicola; Bonassi, Stefano

    2012-07-01

    The objective and background is to confirm in a double-blind, placebo-controlled study the high triptan response rates we had previously reported in an open study in migraine patients with unilateral cranial autonomic symptoms. In this randomized, double-blind, placebo-controlled study 80 migraineurs with unilateral cranial autonomic symptoms were assigned to receive rizatriptan 10 mg wafer or placebo (ratio 1:1) and treated for a single moderate or severe migraine attack. The primary endpoints were pain freedom at 2 h and total migraine freedom at 2 h. Secondary endpoints included pain relief, no associated symptoms and sustained pain freedom or relief. Significantly more patients reported pain freedom at 2 h after taking rizatriptan (54 %) than after placebo (8 %) (therapeutic gain 46 % [28 %; 64 %]; P < 0.001). Similarly, significantly more patients reported total migraine freedom at 2 h after rizatriptan (51 %) than after placebo (8 %) (therapeutic gain 43 % [26 %; 61 %]; P < 0.001). Rizatriptan was also more effective than placebo on most secondary endpoints. We confirm in a placebo-controlled study our previous data suggesting that the presence of unilateral cranial autonomic symptoms in migraineurs predicts a positive response to triptans, probably owing to intense trigeminal peripheral afferent activation which strongly recruits peripheral neurovascular 5-HT1B/1D receptors. Acute and preventive pharmacological trials in migraine should focus also on this subset of migraine patients. PMID:22460943

  8. 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.

  9. From Gaia to NEAT (Theia): synergies and results of the NEAT double-blind experiment

    NASA Astrophysics Data System (ADS)

    Antiche, E.; Voss, H.; Luri, X.; Anglada Escudé, G.; Jordi, C.

    2015-05-01

    The Near-Earth Astrometric Telescope (NEAT, recently renamed into Theia) is a new mission concept to achieve sub-microarcsecond precision astrometry using pointed observations. This mission will be proposed as a candidate for the M4 call of ESA later this year. It will be a natural continuation of ESA's leadership in space astrometry by continuing and extending the work of the very successful HIPPARCOS and the recently launched Gaia missions. The science top-level requirements for NEAT are set by the ability to detect potentially habitable Earth-mass planets around all G and K dwarfs within 10 pc. Given the versatility of the concept, many other science cases can be addressed by obtaining ultra-precise pointed astrometric observations of exotic objects detected by Gaia and other on-going projects. Although Gaia is a mission that is not designed to search for exoplanets per se, it will make a major contribution to the field and to the NEAT mission in several aspects. The Gaia mission will produce an enormous wealth of data to mine and explore, so experience must be acquired to identify the simple traps of the analysis methods, design validation strategies and prepare scientists across the ESA community and beyond to exploit such wealth of data. In fact, the experience in astrometry precision and simulations acquired for Gaia, laid the foundation for the creation of the NEAT simulator. This simulator has been created in order to build a double-blind test program for astrometric planet detection, with the goal to demonstrate the exo-Earth planet finding capabilities of a pointed astrometric mission. Results are presented from our participation in this double-blind test showing our capabilities in the detection of Earth-like planets orbiting nearby Sun-like stars based on the MLE method.

  10. 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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  12. Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

    PubMed Central

    Bonnevie, O; Svendsen, L B; Holst-Christensen, J; Johansen, T S; Søltoft, J; Christiansen, P M

    1979-01-01

    In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer. PMID:385457

  13. Effects of Naloxone and Naltrexone on Self-Injury: A Double-Blind, Placebo-Controlled Analysis.

    ERIC Educational Resources Information Center

    Barrett, Rowland P.; And Others

    1989-01-01

    Double blind study compared effects of two drug treatments, naloxone hydrochloride and naltrexone hydrochloride, on self-injurious behavior of a 12-year-old mentally retarded and autistic girl. Self-injury increased with naloxone treatment but decreased to near zero with naltrexone, a change which persisted at follow-up 22 months after treatment.…

  14. Syrup formulations for post-tonsillectomy analgesia: a double-blind study comparing ibuprofen, aspirin and placebo.

    PubMed

    Parker, D A; Gibbin, K P; Noyelle, R M

    1986-09-01

    Post-tonsillectomy analgesia from ibuprofen, aspirin and placebo is compared in a double-blind study. The results are reported showing ibuprofen to have greater therapeutic benefit than placebo whereas aspirin did not. Methods of providing pain relief after tonsillectomy and the relative clinical merits of ibuprofen and aspirin are discussed. PMID:3531373

  15. The Gluten-Free, Casein-Free Diet in Autism: Results of a Preliminary Double Blind Clinical Trial

    ERIC Educational Resources Information Center

    Elder, Jennifer Harrison; Shankar, Meena; Shuster, Jonathan; Theriaque, Douglas; Burns, Sylvia; Sherrill, Lindsay

    2006-01-01

    This study tested the efficacy of a gluten-free and casein-free (GFCF) diet in treating autism using a randomized, double blind repeated measures crossover design. The sample included 15 children aged 2-16 years with autism spectrum disorder. Data on autistic symptoms and urinary peptide levels were collected in the subjects' homes over the 12…

  16. A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

    ERIC Educational Resources Information Center

    Handen, Benjamin L.; Melmed, Raun D.; Hansen, Robin L.; Aman, Michael G.; Burnham, David L.; Bruss, Jon B.; McDougle, Christopher J.

    2009-01-01

    Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI…

  17. Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

    ERIC Educational Resources Information Center

    Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

    2010-01-01

    Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  19. 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…

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  1. Daylight photodynamic therapy with 1.5% 3-butenyl 5-aminolevulinate gel as a convenient, effective and safe therapy in acne treatment: A double-blind randomized controlled trial.

    PubMed

    Kwon, Hyuck Hoon; Moon, Ki Rang; Park, Seon Yong; Yoon, Ji Young; Suh, Dae Hun; Lee, Jee Bum

    2016-05-01

    While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester, 1.5% 3-butenyl ALA-bu gel, using daylight only as the potential visible light source. Forty-six acne patients were randomly assigned to either ALA-bu or vehicle application group in a double-blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA-bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8, interleukin-1β, matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy. PMID:26660491

  2. Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial

    PubMed Central

    Sohrab, Golbon; Angoorani, Pooneh; Tohidi, Maryam; Tabibi, Hadi; Kimiagar, Masoud; Nasrollahzadeh, Javad

    2015-01-01

    Introduction Diabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D). Materials and methods In a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56±6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12-week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed. Results At baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups. Conclusions The study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress. PMID:26355954

  3. 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

  4. A randomised double-blind placebo-controlled trial investigating the behavioural effects of vitamin, mineral and n-3 fatty acid supplementation in typically developing adolescent schoolchildren.

    PubMed

    Tammam, Jonathan D; Steinsaltz, David; Bester, D W; Semb-Andenaes, Turid; Stein, John F

    2016-01-28

    Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren; hence, correcting them may improve sociability. We therefore tested the effects of vitamin, mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13-16 years (n 196). Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes, using Conners' teacher ratings and school disciplinary records. At baseline, the children's PUFA (n-3 and n-6), vitamin and mineral levels were low, but they improved significantly in the group treated with n-3, vitamins and minerals (P=0·0005). On the Conners disruptive behaviour scale, the group given the active supplements improved, whereas the placebo group worsened (F=5·555, d=0·35; P=0·02). The general level of disciplinary infringements was low, thus making it difficult to obtain improvements. However, throughout the school term school disciplinary infringements increased significantly (by 25 %; Bayes factor=115) in both the treated and untreated groups. However, when the subjects were split into high and low baseline infringements, the low subset increased their offences, whereas the high-misbehaviour subset appeared to improve after treatment. But it was not possible to determine whether this was merely a statistical artifact. Thus, when assessed using the validated and standardised Conners teacher tests (but less clearly when using school discipline records in a school where misbehaviour was infrequent), supplementary nutrition might have a protective effect against worsening behaviour. PMID:26573368

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

    PubMed Central

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

    2013-01-01

    Objective To examine the efficacy of N-acetylcysteine (NAC) for the treatment of pediatric trichotillomania (TTM) in a double-blind, placebo-controlled, add-on study. Method A total of 39 children and adolescents aged 8 to 17 years with pediatric trichotillomania were randomly assigned to receive NAC or matching placebo for 12 weeks. Our primary outcome was change in severity of hairpulling as measured by the Massachusetts General Hospital–Hairpulling Scale (MGH-HPS). Secondary measures assessed hairpulling severity, automatic versus focused pulling, clinician-rated improvement, and comorbid anxiety and depression. Outcomes were examined using linear mixed models to test the treatment × time interaction in an intention-to-treat population. Results No significant difference between N-acetylcysteine and placebo was found on any of the primary or secondary outcome measures. On several measures of hairpulling, subjects significantly improved with time regardless of treatment assignment. In the NAC group, 25% of subjects were judged as treatment responders, compared to 21% in the placebo group. Conclusions We observed no benefit of NAC for the treatment of children with trichotillomania. Our findings stand in contrast to a previous, similarly designed trial in adults with TTM, which demonstrated a very large, statistically significant benefit of NAC. Based on the differing results of NAC in pediatric and adult TTM populations, the assumption that pharmacological interventions demonstrated to be effective in adults with TTM will be as effective in children, may be inaccurate. This trial highlights the importance of referring children with TTM to appropriate behavioral therapy before initiating pharmacological interventions, as behavioral therapy has demonstrated efficacy in both children and adults with trichotillomania. PMID:23452680

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

    PubMed Central

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

    2015-01-01

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

  7. Resistant starch type 4-enriched diet lowered blood cholesterols and improved body composition in a double-blind controlled crossover intervention

    PubMed Central

    Nichenametla, Sailendra N.; Weidauer, Lee A.; Wey, Howard E.; Beare, Tianna M.; Specker, Bonny L.; Dey, Moul

    2014-01-01

    A metabolic health crisis is evident as cardiovascular diseases (CVD) remain the leading cause of mortality in the US. Effects of resistant starch type 4 (RS4), a prebiotic fiber, in comprehensive management of metabolic syndrome (MetS) remain unknown. This study examined the effects of a blinded exchange of resistant starch type-4 (RS4)-enriched flour (30% v/v) with regular/control flour (CF) diet on multiple MetS comorbidities. In a double-blind (participants-investigators), placebo-controlled, cluster crossover intervention (n=86, age ≥18, 2–12week interventions, 2week washout) in the US, individuals were classified as having MetS (With-MetS) or not (No-MetS) following International Diabetes Federation (IDF)-criteria. RS4 consumption compared with CF resulted in 7.2% (p=0.002) lower mean total cholesterol (TC), 5.5% (p=0.04) lower non-HDL, and a 12.8% (p<0.001) lower HDL cholesterol in the With-MetS group. No-MetS individuals had a 2.6% (p=0.02) smaller waist circumference and 1.5% (p=0.03) lower percent body fat following RS4 intervention compared to CF. A small but significant 1% increase in fat-free mass was observed in all participants combined (p=0.02). No significant effect of RS4 was observed for glycemic variables and blood pressures. RS4 consumption improved dyslipidemia and body composition. Incorporation of RS4 in routine diets could offer an effective strategy for public metabolic-CVD health promotion. The clinicaltrials.gov-reference NCT01887964. PMID:24478107

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

    PubMed Central

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

    2015-01-01

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

  9. Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

    PubMed

    Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

    2016-06-01

    The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. PMID:27160199

  10. Protocol and Rationale-The Efficacy of Minocycline as an Adjunctive Treatment for Major Depressive Disorder: A Double Blind, Randomised, Placebo Controlled Trial

    PubMed Central

    Maes, Michael; Ashton, Melanie; Berk, Lesley; Kanchanatawan, Buranee; Sughondhabirom, Atapol; Tangwongchai, Sookjareon; Ng, Chee; Dowling, Nathan; Malhi, Gin S.; Berk, MIchael

    2014-01-01

    While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression. PMID:25598820

  11. A Randomized Double-blind, Placebo Controlled Trial of Venlafaxine-Extended Release for Co-occurring Cannabis Dependence and Depressive Disorders

    PubMed Central

    Levin, Frances R.; Mariani, John; Brooks, Daniel J.; Pavlicova, Martina; Nunes, Edward V.; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A.; Carpenter, Kenneth M.

    2013-01-01

    Aim To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. Design This was a randomized, 12 week, double-blind, placebo-controlled trial of outpatients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. Settings The trial was conducted at two university research centers in the United States. Participants One hundred and three cannabis dependent adults participated in the trial. Measurements The primary outcome measures were 1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and 2) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. Findings The proportion of patients achieving a clinically significant mood improvement [50% decrease in Hamilton Depression score from baseline] was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (X12=0.48, p-value= 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (X12=7.46, p-value<0.01; OR = 4.51, 95% CI: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F1,179=30.49, p-value<0.01), but not the VEN-XR group (F1,186=0.02, p-value=0.89). Conclusions For depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. PMID:23297841

  12. 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

  13. 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

  14. A double-blind, randomized, and active-controlled phase III study of Herbiron drink in the treatment of iron-deficiency anemia in premenopausal females in Taiwan

    PubMed Central

    Lee, Ching-Tzu; Jeng, Cherng-Jye; Yeh, Lian-Shung; Yen, Ming-Shyen; Chen, Shih-Ming; Lee, Chyi-Long; Lin, Willie; Hsu, Chun-Sen

    2016-01-01

    Background About 468 million non-pregnant women are estimated to suffer from iron-deficiency anemia (IDA) worldwide. The highest prevalence of IDA occurs in the Taiwanese population. Objective To evaluate the effectiveness of Herbiron to increase iron absorption in women with IDA. Design Phase III double-blind, randomized, active-controlled, and parallel comparative study enrolled 124 patients with IDA and consisted of a 2-week run-in period, randomization, 12 weeks of supplementation, and 4 weeks of follow-up. The treatment group received Herbiron drink 50 mL p.o., b.i.d., before meals (daily iron intake: 21 mg/day) plus placebo tablets. The control group received a ferrous sulfate tablet, t.i.d., plus placebo 50-mL drink before meals (daily iron intake: 195 mg/day). Results Both treatments significantly improved hemoglobin and all secondary efficacy endpoints. Most IDA patients treated with Herbiron or ferrous sulfate finished the study in the normal range. Ferrous sulfate treatment induced a rapid rate of hemoglobin synthesis, which plateaued by week 8, whereas Herbiron treatment increased the rate of hemoglobin synthesis more slowly, likely due to its nine-fold lower iron content. Gastrointestinal adverse events (diarrhea, abdominal pain, dyspepsia, and nausea) but not infectious adverse events were significantly more common in the ferrous sulfate group (n=11, 18.3%) than those in the Herbiron group (n=1, 1.6%) (p=0.004). Conclusion Twelve weeks of Herbiron treatment delivering 21mg of iron or ferrous sulfate treatment delivering 195 mg of iron induced normal hemoglobin levels in 62 or 91% of non-pregnant women with IDA in Taiwan, respectively, suggesting dose-dependent and bioavailability effects. PMID:27343206

  15. Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial

    PubMed Central

    Pan, An; Sun, Jianqin; Chen, Yanqiu; Ye, Xingwang; Li, Huaixing; Yu, Zhijie; Wang, Yanfang; Gu, Wenjia; Zhang, Xinyi; Chen, Xiafei; Demark-Wahnefried, Wendy; Liu, Yong; Lin, Xu

    2007-01-01

    Background Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients. Methodology/Principal Findings This was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA1c (-0.10±0.65 % vs. 0.09±0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2±18.1 vs. 1.2±2.4 µg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations. Conclusions/Significance Daily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes. Trial Registration ClinicalTrials.gov NCT00363233 PMID:17987126

  16. 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

  17. Chuanhu Anti-Gout Mixture versus Colchicine for Acute Gouty Arthritis: A Randomized, Double-Blind, Double-Dummy, Non-Inferiority Trial

    PubMed Central

    Wang, YanGang; Wang, Luan; Li, EnZe; Li, Yang; Wang, ZhongChao; Sun, XiaoFang; Yu, XiaoLong; Ma, Lin; Wang, YunLong; Wang, YouXin

    2014-01-01

    Background The Chuanhu anti-gout mixture has been used for many years in the treatment of gout in Chinese Traditional Medicine, and current methods for treatments for acute gouty arthritis have been either less effective or have had serious side effects. Methods In this 12-week, double-blind, double-dummy, non-inferiority study, outpatient individuals with newly diagnosed acute gouty arthritis were randomly assigned to receive Chuanhu anti-gout mixture or colchicine. Both the study investigators and the participants were masked to the treatment assignments. The primary outcome was the recurrence rate of acute gouty arthritis, and the secondary outcomes were changes in white blood cells (WHC) and C-reactive protein (CRP). This trial is registered at ISRCTN.org as trial ISRCTN65219941. Results A total of 176 patients were randomly assigned to receive either the Chuanhu anti-gout mixture or Colchicine. The overall recurrence rates in the Chuanhu anti-gout mixture group (CH group) and the Colchicine group (Col group) were 12.50% vs 14.77% (difference -2.22%, 95% confidence interval (95% CI): -10.78%~6.23%), meeting the predefined non-inferiority criterion of 15%, as did the data for WHC and CRP. The incidence of adverse events (mainly diarrhea) was less in the Col group than in the CH group (2.27% vs 28.41%, 95% CI 0.01~0.26). In addition, changes in blood uric acid, alanine aminotransferase, aspartate aminotransferase and creatinine in the CH group were significantly larger compared to those in the Col group (P<0.05). Conclusions The Chuanhu anti-gout mixture was non-inferior to colchicine for the treatment of acute gouty arthritis. The study suggested that the Chuanhu anti-gout mixture can be considered an alternative choice for the treatment of acute gouty arthritis because of its lower incidence of adverse events and its protection of kidney and renal function. PMID:25013367

  18. Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial

    PubMed Central

    Al-Sofiani, Mohammed E.; Jammah, Anwar; Racz, Michael; Khawaja, Rajab A.; Hasanato, Rana; El-Fawal, Hassan A. N.; Mousa, Shaker A.; Mason, Darius L.

    2015-01-01

    Background: Diabetes mellitus (DM) and vitamin D deficiency are major health concerns around the world. Evidence suggests a possible role of vitamin D in improvement of insulin secretion and sensitivity. Objectives: We assessed whether vitamin D supplementation could be used in vitamin D deficient-type II diabetes to improve glucose metabolism, components of metabolic syndrome (MetS) and specific inflammatory biomarkers. Patients and Methods: A double blind, randomized clinical trial was conducted in King Khalid University Hospital, Saudi Arabia to evaluate the effect of cholecalciferol supplementation on glycemic control, MetS components and specific inflammatory biomarkers including tumor necrosis factor-alpha (TNF-α), Interleukin (IL-6), leptin, adiponectin and vascular cell adhesion molecule-1 (VCAM-1). Twenty-two patients with type II diabetes with insulin resistance, glycated hemoglobin (HbA1c) ≥ 6 (42 mmol/mol) and serum 25(OH)D < 50 nmol/L were randomized using a computer program to receive either supplementation with cholecalciferol (5000 IU/day) or placebo for 12 weeks. The primary outcome was change in HbA1c levels from baseline. Results: Median [IQR] 25(OH)D levels increased significantly in the vitamin D group as 58.1 [48, 67.3] nmol/L (P = 0.002). There was no significant difference in the change of HbA1c between the groups (P = 0.5) with a decrease of -0.1% [-1, 0.5] in the vitamin D group and an increase of 0.15% [0.1, 0.2] in the placebo group. A significant improvement was observed in the homeostasis model of assessment of β-cell activity (HOMA-%B) (P = 0.03) with vitamin D supplementation compared to baseline. Conclusions: Vitamin D repletion for 12 weeks increased serum vitamin D concentrations and improved β-cell activity in vitamin D-deficient type II diabetes with no significant changes in HbA1c or insulin sensitivity. PMID:25745497

  19. A placebo-controlled, double-blind clinical trial to evaluate the efficacy of Imedeen® Time Perfection® for improving the appearance of photodamaged skin

    PubMed Central

    Stephens, Thomas J; Sigler, Monya L; Herndon, James H; Dispensa, Lisa; Le Moigne, Anne

    2016-01-01

    Objective To assess the efficacy of Imedeen Time Perfection for improving the appearance and condition of photoaged skin in healthy women. Methods This randomized, double-blind, placebo-controlled clinical trial enrolled healthy women, 35–60 years of age, with Fitzpatrick I–III and Glogau II–III skin types and mild-to-moderate facial fine lines/wrinkles. The eligible subjects were randomized to receive two tablets daily of either Imedeen Time Perfection (Imedeen) or a matching placebo for 12 weeks. Efficacy assessments included investigator rating of 16 photoaging parameters (ie, global facial appearance and 15 individual facial parameters and the average of all parameters), instrumentation (ie, ultrasound dermal density, moisture level of the stratum corneum, transepidermal water loss, cutometry), and subjects’ self-assessment. Differences in the mean change from baseline to week 12 values on these outcomes were compared between Imedeen and placebo using analysis of variance or a paired t-test. Results Seventy-four subjects with primarily Fitzpatrick skin type III (78%–79%) and Glogau type III (53%–58%) completed the study (Imedeen: n=36; placebo: n=38). The mean difference in change from baseline to week 12 for global facial assessment significantly favored Imedeen over placebo (−0.52; P=0.0017). Additionally, the mean differences in the average of all facial photoaging parameters (−0.29), mottled hyperpigmentation (−0.25), tactile laxity (−0.24), dullness (−0.47), and tactile roughness (−0.62) significantly favored Imedeen over placebo (P≤0.05). Significantly greater increases in ultrasound dermal density (+11% vs +1%; P≤0.05) and stratum corneum moisturization (+30% vs +6%; P≤0.05) were also observed for Imedeen than for placebo. There were no significant differences on other instrumental outcomes. Conclusion The results of this study suggest that Imedeen Time Perfection can positively affect the appearance of photoaged skin

  20. 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

  1. A double-blind atropine trial for active learning of autonomic function.

    PubMed

    Fry, Jeffrey R; Burr, Steven A

    2011-12-01

    Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to concomitantly convey the importance of bias in experimentation by adopting a double-blind placebo-controlled approach. We have used this class effectively in various forms with ∼600 students receiving atropine over the last 16 yr. This class has received favorable feedback from staff and students of medicine, pharmacy, and neuroscience, and we recommend it for such undergraduates. The learning objectives that students are expected to achieve are to be able to 1) know the ethical, safety, and hygiene requirements for using human volunteers as subjects; 2) implement and explain a double-blind placebo-controlled trial; 3) design, agree, and execute a protocol for making (and accurately recording) precise reproducible measurements of pulse rate, pupil diameter, and salivary flow; 4) evaluate the importance of predose periods and measurement consistency to detect effects (including any reversibility) after an intervention; 5) experience direct cause-and-effect relationships integrating physiology with pharmacology in people; 6) calculate appropriate summary statistics to describe the data and determine the data's statistical significance; 7) recognize normal variability both within and between subjects in baseline physiological parameters and also recognize normal variability in response to pharmacological treatment; 8) infer the distribution and role of muscarinic receptors in the autonomic nervous system with respect to the heart, eye, and mouth; 9) identify and explain the clinical significance of differences in effect due to the route and formulation of atropine; 10) produce and deliver a concise oral presentation of

  2. 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

  3. Evaluation of the Effects of Pinus koraiensis Needle Extracts on Serum Lipid and Oxidative Stress in Adults with Borderline Dyslipidemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

    PubMed Central

    Kim, Hyerang; Choue, Ryowon

    2016-01-01

    Background. Dyslipidemia has been well-known as a common metabolic disorder contributing to cardiovascular disease. The aim of this study was to evaluate the effect of the Pinus koraiensis needle extracts (PKE) on the blood cholesterol and oxidative stress. Method. We conducted a 12-week randomized, double-blinded controlled trial to examine the effect of PKE on blood lipid profiles in adults with borderline dyslipidemia. Thirty-three eligible persons were recruited and randomly assigned into PKE (n = 20) and placebo groups (n = 13). Serum lipids including total cholesterol, low-density lipoprotein- (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, and triglyceride were measured before and after trial. Serum insulin, glucose, and antioxidant indicators were also analyzed before and after trial and anthropometry and blood pressure were measured every 4 weeks. Results. After 12 weeks, PKE statically significant decreases in systolic blood pressure (p < 0.05) and waist circumference (p < 0.05) were observed. Also, VLDL-cholesterol significantly decreased (from 24.4 ± 10.0 mg/dL at baseline to 18.4 ± 4.1 mg/dL after 12 weeks) (p < 0.05) and superoxide dismutase (SOD) increased (6.12 ± 0.41 U/mL to 9.06 ± 0.62 U/mL) (p < 0.01) in PKE group. However, after adjustment with WC, VLDL-cholesterol was not significant between groups (p = 0.095) and while SOD remained significant between groups (p = 0.013). Conclusion. The results show that PKE was effective in improving the superoxide dismutase in the individuals with borderline dyslipidemia. PMID:27610187

  4. Evaluation of the Effects of Pinus koraiensis Needle Extracts on Serum Lipid and Oxidative Stress in Adults with Borderline Dyslipidemia: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

    PubMed

    Lee, Hansongyi; Kim, Hyerang; Choue, Ryowon; Lim, Hyunjung

    2016-01-01

    Background. Dyslipidemia has been well-known as a common metabolic disorder contributing to cardiovascular disease. The aim of this study was to evaluate the effect of the Pinus koraiensis needle extracts (PKE) on the blood cholesterol and oxidative stress. Method. We conducted a 12-week randomized, double-blinded controlled trial to examine the effect of PKE on blood lipid profiles in adults with borderline dyslipidemia. Thirty-three eligible persons were recruited and randomly assigned into PKE (n = 20) and placebo groups (n = 13). Serum lipids including total cholesterol, low-density lipoprotein- (LDL-) cholesterol, high-density lipoprotein- (HDL-) cholesterol, very low-density lipoprotein- (VLDL-) cholesterol, and triglyceride were measured before and after trial. Serum insulin, glucose, and antioxidant indicators were also analyzed before and after trial and anthropometry and blood pressure were measured every 4 weeks. Results. After 12 weeks, PKE statically significant decreases in systolic blood pressure (p < 0.05) and waist circumference (p < 0.05) were observed. Also, VLDL-cholesterol significantly decreased (from 24.4 ± 10.0 mg/dL at baseline to 18.4 ± 4.1 mg/dL after 12 weeks) (p < 0.05) and superoxide dismutase (SOD) increased (6.12 ± 0.41 U/mL to 9.06 ± 0.62 U/mL) (p < 0.01) in PKE group. However, after adjustment with WC, VLDL-cholesterol was not significant between groups (p = 0.095) and while SOD remained significant between groups (p = 0.013). Conclusion. The results show that PKE was effective in improving the superoxide dismutase in the individuals with borderline dyslipidemia. PMID:27610187

  5. Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

    PubMed

    Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya'acov, A Ben; Shabbat, Y; Ilan, Y

    2015-08-01

    Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. PMID:25846055

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

    PubMed Central

    2010-01-01

    Background A double blind, randomized, placebo controlled study to evaluate the safety and efficacy of the naturally derived topical oil, "Neuragen PN®" for the treatment of neuropathic pain. Methods Sixty participants with plantar cutaneous (foot sole) pain due to all cause peripheral neuropathy were recruited from the community. Each subject was randomly assigned to receive one of two treatments (Neuragen PN® or placebo) per week in a crossover design. The primary outcome measure was acute spontaneous pain level as reported on a visual analog scale. Results There was an overall pain reduction for both treatments from pre to post application. As compared to the placebo, Neuragen PN® led to significantly (p < .05) greater pain reduction. Fifty six of sixty subjects (93.3%) receiving Neuragen PN® reported pain reduction within 30 minutes. This reduction within 30 minutes occurred in only twenty one of sixty (35.0%) subjects receiving the placebo. In a break out analysis of the diabetic only subgroup, 94% of subjects in the Neuragen PN® group achieved pain reduction within 30 minutes vs 11.0% of the placebo group. No adverse events were observed. Conclusions This randomized, placebo controlled, clinical trial with crossover design revealed that the naturally derived oil, Neuragen PN®, provided significant relief from neuropathic pain in an all cause neuropathy group. Participants with diabetes within this group experienced similar pain relief. Trial registration ISRCTN registered: ISRCTN13226601 PMID:20487567

  7. 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

  8. Efficacy of total lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized trial

    SciTech Connect

    Strober, S.; Tanay, A.; Field, E.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.; Brown, B.W.; Kaplan, H.S.

    1985-04-01

    Twenty-six patients participated in a randomized, double-blind study of the efficacy of total lymphoid irradiation in the treatment of intractable rheumatoid arthritis. All 26 patients, for whom therapy with gold compounds and penicillamine had failed, would ordinarily have been considered candidates for cytotoxic or antimetabolite drug therapy. Thirteen patients randomly assigned to receive full-dose total lymphoid irradiation (2000 rad) and 11 patients assigned to receive control low-dose total lymphoid irradiation (200 rad) completed radiotherapy. Alleviation of joint disease activity was significantly greater in the high-dose group as judged by morning stiffness, joint tenderness, and functional assessment (global composite score) at 3 and 6 months after radiotherapy. The high-dose group had a marked reduction in both T-lymphocyte function and numbers, but this finding was not observed in the low-dose group. Complications seen in the high-dose but not low-dose group included transient neutropenia, thrombocytopenia, pericarditis, and pleurisy.

  9. Carbohydrate craving: a double-blind, placebo-controlled test of the self-medication hypothesis.

    PubMed

    Corsica, Joyce A; Spring, Bonnie J

    2008-12-01

    Carbohydrate craving, the overwhelming desire to consume carbohydrate-rich foods in an attempt to improve mood, remains a scientifically controversial construct. We tested whether carbohydrate preference and mood enhancement could be demonstrated in a double-blind, placebo-controlled self-administration trial. Overweight females who met strict operational criteria for carbohydrate craving participated in two 3-day discrete choice trials over a 2-week period. Participants reported their mood before and at several time points after undergoing a dysphoric mood induction and ingesting, either a carbohydrate beverage or a taste and calorie-matched protein-rich balanced nutrient beverage. Every third testing day, participants were asked to self-administer the beverage they preferred based on its previous mood effect. Results showed that, when rendered mildly dysphoric, carbohydrate cravers chose the carbohydrate beverage significantly more often than the protein-rich beverage and reported that carbohydrate produced greater mood improvement. The carbohydrate beverage was perceived as being more palatable by the carbohydrate cravers, although not by independent taste testers who performed the pre-trial taste matching. This study, performed under rigorous study conditions, supports the existence of a carbohydrate craving syndrome in which carbohydrate self-administration improves mildly dysphoric mood. PMID:18928908

  10. Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial

    PubMed Central

    Ciliberto, Heather; Ciliberto, Michael; Briend, Andreé; Ashorn, Per; Bier, Dennis; Manary, Mark

    2005-01-01

    Objective To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Design Prospective, double blind, placebo controlled trial randomised by household. Setting 8 villages in rural southern Malawi. Participants 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed the trial. Intervention Daily supplementation with an antioxidant powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose that provided about three times the recommended dietary allowance of each nutrient or placebo for 20 weeks. Main outcome measures The primary outcome was the incidence of oedema. Secondary outcomes were the rates of change for weight and length and the number of days of infectious symptoms. Results 62 children developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk 1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in rates of weight or height gain. Children who received antioxidant supplementation did not experience less fever, cough, or diarrhoea. Conclusions Antioxidant supplementation at the dose provided did not prevent the onset of kwashiorkor. This finding does not support the hypothesis that depletion of vitamin E, selenium, cysteine, or riboflavin has a role in the development of kwashiorkor. PMID:15851401

  11. Effect of prophylactic antibiotics in acute nonperforated appendicitis: a prospective, randomized, double-blind clinical study.

    PubMed Central

    Busuttil, R W; Davidson, R K; Fine, M; Tompkins, R K

    1981-01-01

    A prospective, randomized, double-blind clinical study was performed to determined the efficacy of short-term (24 hr) perioperative antibiotics in preventing septic complications after emergency appendectomy for nonperforated appendicitis. The patients were stratified into three clinical arms: Group I (placebo, n = 45), Group II (cefamandole, n = 46) and Group III (cefamandole plus carbenicillin, n = 45). The three groups of patients were similar in regard to age, sex, duration of operation and pathologic classification of the appendix. The overall incidence of infection in the study was 5.1%. The infection rates in Groups II (2.2%) and III (0%) were significantly lower than Group I (placebo) (13.3%), (p less than 0.05). No difference was observed between cefamandole alone and cefamandole plus carbenicillin. Average postoperative hospital days per patient for each group was: Group I - 3.8 days; Group II - 2.9 days; Group III - 3.1 days. Cost analysis of hospitalization including cost of prophylactic antibiotics revealed a $247.99 per patient saving for Group II versus Group I and $95.53 for Group III versus Group I. Systemic prophylactic antibiotics can successfully reduce septic complications after appendectomy for nonperforated appendicitis, and a single drug (cefamandole) directed at the facultative pathogens is as effective as double drug therapy, which includes specific anaerobic coverage. PMID:7025769

  12. A double-blind study of the effect on hemostasis of nabumetone (Relafen) compared to placebo.

    PubMed

    Jennings, M B; Alfieri, D M; Jules, K T; Lesczczynski, C

    2000-01-01

    A double-blind, placebo-controlled clinical trial comparing the effect on hemostasis of nabumetone (Relafen) to placebo in patients who were about to undergo forefoot surgery was performed. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to inhibit platelet cyclooxygenase activity, resulting in altered platelet function and thus potentially enhanced bleeding. Nabumetone has been reported to have no effect on platelet aggregation and bleeding time in normal volunteers and in patients who have undergone knee arthroscopy. After fulfilling the inclusion criteria and after a 1-week washout period (acetaminophen controlled), 15 patients were enrolled in the nabumetone group and 15 patients were randomized in the placebo group. Hemostatic parameters [prothrombin time (PT), partial thromboplastin time (PTT), and Ivy bleeding time (IBT)] were assessed at baseline, visit 2, visit 3, and final visit. No meaningful differences were observed between treatment groups in any of the measured hemostatic parameters. No significant adverse events were reported. There was no significant change from baseline for PT, PTT, and IBT in the nabumetone group (PT, p < .06; PTT, p < .64; IBT, p < .17) versus the placebo group (PT, p < .61; PTT, p < .63; IBT, p < .25). The lack of bleeding diathesis and significant prolongation of PT, PTT, or IBT in this study suggests that nabumetone in dosages up to 1000 mg/day can be administered safely in the immediate preoperative period to patients undergoing forefoot surgery. PMID:10862388

  13. Local Infiltration Analgesia reduces pain and hospital stay after primary TKA: randomized controlled double blind trial.

    PubMed

    Vaishya, Raju; Wani, Ajaz Majeed; Vijay, Vipul

    2015-12-01

    Postoperative analgesia following Total Knee Arthroplasty (TKA) with the use of parenteral opioids or epidural analgesia can be associated with important side effects. Good perioperative analgesia facilitates faster rehabilitation, improves patient satisfaction, and may reduce the hospital stay. We investigated the analgesic effect of a locally injected mixture of drugs, in a double blinded RCT in 80 primary TKA. They were randomized either to receive a periarticular mixture of drugs containing bupivacaine, ketorolac, morphine, and adrenalline or to receive normal saline. Visual analog scores (VAS) for pain (at rest and during activity) and for patient satisfaction and range of motion were recorded postoperatively. The patients who had received the periarticular injection used significantly less the Patient Controlled Analgesia (PCA) after the surgery as compared to the control group. In addition, they had lower VAS for pain during rest and activity and higher visual analog scores for patient satisfaction 72 hours postoperatively. No major complication related to the drugs was observed. Intraoperative periarticular injection with multimodal drugs following TKA can significantly reduce the postoperative pain and hence the requirements for PCA and hospital stay, with no apparent risks. PMID:26790796

  14. 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

  15. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study.

    PubMed

    Bozzetti, F; Biganzoli, L; Gavazzi, C; Cappuzzo, F; Carnaghi, C; Buzzoni, R; Dibartolomeo, M; Baietta, E

    1997-01-01

    The purpose of this study was to evaluate the efficacy of glutamine in preventing doxifluridine-induced diarrhea and the potential impact of glutamine on the tumor growth. We investigated 65 patients with advanced breast cancer receiving doxifluridine in a double-blind randomized fashion: 33 patients took glutamine (30 g/d, divided in 3 doses of 10 g each) for 8 consecutive days (5-12h) during each interval between chemotherapy, which was administered from day 1 to 4. Thirty-two patients took an equal dose of placebo (maltodextrine). The incidence of diarrhea was registered after each cycle of chemotherapy and severity was scored by the National Cancer Institute (NCI), Bethesda, Maryland, classification. The tumor response was evaluated by the World Health Organization (WHO) criteria. A total of 278 and 259 cycles (median 10 cycles), respectively, were delivered in glutamine and placebo groups. There were 34 and 32 episodes of diarrhea in glutamine and placebo groups, with no statistical difference overall, in the severity and duration of tumor growth, there was no difference in the response rate (21% and 28% of complete or partial response, respectively), in median time to response (2 mo), or in median duration of response. In conclusion, glutamine did not prevent the occurrence of the doxifluridine-induced diarrhea and did not have any impact on tumor response to chemotherapy. PMID:9263281

  16. [Auriculo-electropuncture in rheumatoid arthritis (a double-blind study)].

    PubMed

    Ruchkin, I N; Burdeĭnyĭ, A P

    1987-01-01

    A study of the efficacy of auriculo-electropuncture (AEP) by a double blind method was conducted in 16 patients with rheumatoid arthritis (RA). Points on the auricle were looked for by means of an device of individual use. After that during true AEP (the study group of 10 patients) the device was switched on to the stimulation mode, during false AEP (the control group of 6 patients) it was switched off. Each patient was given 10 procedures except one patient of the study group in whom treatment had to be discontinued after the 3rd procedure because of the development of phlebitis of the left crural veins. Subjective assessment showed improvement in all the patients of the study group (considerable improvement in 2 patients), in the control group improvement was noted in one patient only, no effect--in 3 patients, deterioration--in 2 patients; objective assessment showed improvement in 6 (considerable improvement in one patient) and in one patient, no effect--in 2 and 2, deterioration in one and 3, respectively. In the study group a positive time course of all 8 indices characterizing a degree of pain and inflammatory activity was noted (it was statistically significant for 7 of them), in the control group a positive time course of 3 indices was noted, 5 indices grew worse. A statistically significant decrease in the initially elevated level of blood alpha (2)-globulin was noted against a background of true AEP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3328905

  17. Randomised double-blind comparative study of dexmedetomidine and tramadol for post-spinal anaesthesia shivering

    PubMed Central

    Mittal, Geeta; Gupta, Kanchan; Katyal, Sunil; Kaushal, Sandeep

    2014-01-01

    Background and Aims: Dexmedetomidine (α2 adrenergic agonist) has been used for prevention of post anaesthesia shivering. Its use for the treatment of post-spinal anaesthesia shivering has not been evaluated. The aim of this study was to evaluate and compare the efficacy, haemodynamic and adverse effects of dexmedetomidine with those of tramadol, when used for control of post-spinal anaesthesia shivering. Methods: A prospective, randomised, and double-blind study was conducted in 50 American Society of Anaesthesiologists Grade I and II patients of either gender, aged between 18 and 65 years, scheduled for various surgical procedures under spinal anaesthesia. The patients were randomised in two groups of 25 patients each to receive either dexmedetomidine 0.5 μg/kg or tramadol 0.5 mg/kg as a slow intravenous bolus. Grade of shivering, onset of shivering, time for cessation of shivering, recurrence, response rate, and adverse effects were observed at scheduled intervals. Unpaired t-test was used for analysing the data. Results: Time taken for cessation of shivering was significantly less with dexmedetomidine when compared to tramadol. Nausea and vomiting was observed only in tramadol group (28% and; 20% respectively). There was not much difference in the sedation profile of both the drugs. Conclusion: We conclude that although both drugs are effective, the time taken for cessation of shivering is less with dexmedetomidine when compared to tramadol. Moreover, dexmedetomidine has negligible adverse effects, whereas tramadol is associated with significant nausea and vomiting. PMID:25024466

  18. ANTIPLAQUE AND ANTIGINGIVITIS EFFECT OF LIPPIA SIDOIDES. A DOUBLE-BLIND CLINICAL STUDY IN HUMANS

    PubMed Central

    Rodrigues, Ítalo Sarto Carvalho; Tavares, Vinícius Nascimento; Pereira, Sérgio Luís da Silva; da Costa, Flávio Nogueira

    2009-01-01

    Objectives: The antiplaque and antigingivitis effect of Lippia Sidoides (LS) was evaluated in this in vivo investigation. Material and Methods: Twenty-three subjects participated in a cross-over, double-blind clinical study, using 21-day partial-mouth experimental model of gingivitis. A toothshield was constructed for each volunteer, avoiding the brushing of the 4 experimental posterior teeth in the lower left quadrant. The subjects were randomly assigned initially to use either the placebo gel (control group) or the test gel, containing 10% LS (test group). Results: The clinical results showed statistically significant differences for plaque index (PLI) (p<0.01) between days 0 and 21 in both groups, however only the control group showed statistically significant difference (p<0.01) for the bleeding (IB) and gingival (GI) index within the experimental period of 21 days. On day 21, the test group presented significantly better results than the control group with regard to the GI (p<0.05). Conclusions: The test gel containing 10% LS was effective in the control of gingivitis. PMID:19936516

  19. Multicentre, double-blind comparison of terfenadine and cetirizine in patients with seasonal allergic rhinitis.

    PubMed

    Backhouse, C I; Renton, R; Fidler, C; Rosenberg, R M

    1990-03-01

    This double-blind, multicentre study was designed to compare the efficacy and tolerability of terfenadine 120 mg with cetirizine 10 mg, each taken once daily, in the treatment of seasonal allergic rhinitis. Two hundred and eighty-five patients were recruited to the study by nine general practice centres in the south of England during the 1989 hay-fever season. Symptom severity was assessed daily by the patient and before and after the one-week treatment period by the investigator. At the second clinic visit both patient and investigator assessed the overall response to treatment. The two treatment groups were well matched for all demographic variables and baseline symptom scores. Improvement in all seven symptoms (nasal congestion, sneezing, rhinorrhoea, itching nose, itching eyes, watery eyes and red eyes) and overall response to treatment were similar in both treatment groups. Adverse events were mainly of mild to moderate severity and were reported by 14 patients on terfenadine and 21 patients treated with cetirizine (p = 0.317). This study confirmed terfenadine's role as the treatment of choice in hayfever. A single 120 mg dose in the morning effectively reduced symptoms by 43 to 70 per cent of baseline values, with an acceptably low incidence of side effects. Cetirizine at a single dose of 10 mg displayed equal efficacy in controlling hayfever symptoms but, in common with other studies, had a significantly greater incidence of drowsiness (p = 0.046). PMID:1971516

  20. [Value of hydroxyzine in generalized anxiety disorder: controlled double-blind study versus placebo].

    PubMed

    Ferreri, M; Hantouche, E G; Billardon, M

    1994-01-01

    A multi-centre study was designed to evaluate the efficacy of hydroxyzine in the treatment of patients presenting a generalized anxiety disorder (GAD). One hundred and thirty three patients, suffering from a GAD (according to DSM III-R criteria with 6 months duration criteria), were enrolled in a randomised, double-blind, hydroxyzine (50 mg/day) versus placebo, over a 4-week trial period. By the end of the first week, the decrease of anxiety scores was significant for the hydroxyzine group, as compared to placebo (in respect of all rating criteria of anxiety). The statistical superiority for hydroxyzine continued to the end of the 4-weeks study period, and persisted at a further evaluation a week after abrupt discontinuation of active treatment. The tolerance evaluation showed that side effects were reported in 52% of hydroxyzine group versus 35% of placebo group. The most commun side effects were sleepiness (28% vs 14% with placebo), weight gain (12% vs 10%), dry mouth (14% vs 5%), loss of concentration (9% vs 8%) and insomnia (9% vs 6%). Sleepiness in the hydroxyzine group appeared during the first week and progressively disappeared later during treatment. We concluded that hydroxyzine at 50 mg/day produces a statistically and clinically significant anxiolytic effect, commencing during the first week of treatment and maintained throughout the 4-week period and after abrupt discontinuation without rebound of anxiety or withdrawal symptoms. The most commun side effect with hydroxyzine is transient sleepiness. PMID:7875114

  1. Mifepristone 5 mg versus 10 mg for emergency contraception: double-blind randomized clinical trial

    PubMed Central

    Carbonell, Josep Lluis; Garcia, Ramon; Gonzalez, Adriana; Breto, Andres; Sanchez, Carlos

    2015-01-01

    Purpose To estimate the efficacy and safety of 5 mg and 10 mg mifepristone for emergency contraception up to 144 hours after unprotected coitus. Methods This double-blind randomized clinical trial was carried out at Eusebio Hernandez Hospital (Havana, Cuba). A total of 2,418 women who requested emergency contraception after unprotected coitus received either 5 mg or 10 mg mifepristone. The variables for assessing efficacy were the pregnancies that occurred and the fraction of pregnancies that were prevented. Other variables assessed were the side effects of mifepristone, vaginal bleeding, and changes in the date of the following menstruation. Results There were 15/1,206 (1.2%) and 9/1,212 (0.7%) pregnancies in the 5 mg and 10 mg group, respectively (P=0.107). There were 88% and 93% prevented pregnancies in the 5 mg and un ≥7 days was experienced by 4.9% and 11.0% of subjects in the 5 mg and 10 mg group, respectively (P=0.001). There was a significant high failure rate for women weighing >75 kg in the 5 mg group. Conclusion It would be advisable to use the 10 mg dose of mifepristone for emergency contraception as there was a trend suggesting that the failure rate of the larger dose was lower. PMID:25624773

  2. Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.

    PubMed Central

    Barker, D. P.; Simpson, J.; Pawula, M.; Barrett, D. A.; Shaw, P. N.; Rutter, N.

    1995-01-01

    AIMS--To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. METHODS--Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. RESULTS--Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. CONCLUSIONS--Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective. PMID:7552591

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

    PubMed Central

    Tiralongo, E.; Lea, R. A.; Wee, S. S.; Hanna, M. M.; Griffiths, L. R.

    2012-01-01

    Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides) or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P < 0.0005). However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P = 0.05) during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights. PMID:22229040

  4. Double-blind comparison of moclobemide, imipramine and placebo in depressive patients.

    PubMed

    Ucha Udabe, R; Márquez, C A; Traballi, C A; Portes, N

    1990-01-01

    In a prospective, randomized double-blind study, moclobemide was compared with imipramine and placebo in the treatment of depressed outpatients. Three parallel groups of 24 patients each received capsules containing 100 mg moclobemide, 33 mg imipramine or placebo for 6 weeks; the maximum daily dose was 6 capsules. The only concomitant psychotropic medication allowed was diazepam for severe agitation or insomnia, and continuation of established lithium prophylaxis; no tyramine restrictions were imposed. Both moclobemide and imipramine were clearly superior to placebo in reducing depressive symptoms, moclobemide showing a somewhat faster response on the Hamilton Rating Scale for Depression than imipramine; the mean final improvement in total score compared with baseline was 48.3% for moclobemide, 50.2% for imipramine and 18.6% for placebo. The difference between moclobemide and imipramine was not significant. Placebo was clearly better tolerated than either active drug, and moclobemide slightly but not significantly better than imipramine. A 52-week assessment in 22 of the patients receiving moclobemide showed that the clinical response was maintained and the long-term treatment was well tolerated. It is concluded that both moclobemide and imipramine were superior to placebo in treatment of major depressive episodes in outpatients. There was a slight tendency to earlier response with moclobemide, probably because it can be given in the full dose from the start of treatment. PMID:2123367

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

    PubMed Central

    2014-01-01

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

  6. Clinical study of Tribulus terrestris Linn. in Oligozoospermia: A double blind study.

    PubMed

    Sellandi, Thirunavukkarasu M; Thakar, Anup B; Baghel, Madhav Singh

    2012-07-01

    Infertility is a problem of global proportions, affecting on an average 8-12% of couples worldwide. Low sperm count (Oligozoospermia) is one of the main causes of male infertility and it is correlated with Kshina Shukra. The fruits of Gokshura (Tribulus terrestris. Linn) are considered to act as a diuretic and aphrodisiac; they used for urolithiasis, sexual dysfunctions, and infertility. Hence, it was planned to study the effect of Gokshura in the management of Kshina Shukra (Oligozoospermia), and to evade the preconception, a double-blind, randomized, placebo-controlled study was designed. In this study, eligible subjects between the age of 21 and 50 years, with a complaint of Kshina Shukra (Oligozoospermia), were randomized to receive either Gokshura granules or placebo granules for 60 days. The primary outcome measures were percentage changes in the Pratyatmaka Lakshanas (cardinal symptoms) of Kshina Shukra, Agni bala, Deha bala, Satva bala, the semenogram, and in the Quality of the Sexual Health Questionnaire. The placebo granules showed 70.95% improvement, whereas, the Gokshura granules showed 78.11% improvement in Rogi bala (Agni bala, Deha bala, Satva bala, and the Quality of Sexual Health) and Rogabala (Semen Analysis and Pratyatmaka Lakshanas). The Gokshura granules have shown superior results in the management of Kshina Shukra, as compared to the placebo granules. PMID:23723641

  7. Cibenzoline versus flecainide in the prevention of paroxysmal atrial arrhythmias: a double-blind randomized study.

    PubMed

    Babuty, D; D'Hautefeuille, B; Scheck, F; Mycinsky, C; Pruvost, P; Peraudeau, P

    1995-05-01

    In a randomized, double-blind, parallel clinical trial, the authors tested and compared flecainide and cibenzoline, a new antiarrhythmic drug, on atrial arrhythmias. Sixty-eight patients (36 men, 32 women, mean age 62.5 +/- 1.6 years) with documented symptomatic paroxysmal atrial arrhythmias (fibrillation in 56, flutter in 12) were recruited and received either cibenzoline 260 mg/day (n = 33) or flecainide 200 mg/day (n = 35). Patients were assessed with physical examination, resting ECG, 24-hour ambulatory ECG recording, two-dimensional echocardiography, and standard biologic titrations before the inclusion day, and 3 months and 6 months after the randomization day. Sixteen patients were withdrawn (7 were lost to follow-up, 7 had side effects, 2 had another medical event). Seventeen patients had documented recurrence of atrial arrhythmia (9 in the cibenzoline group, 8 in the flecainide group) during the study. The efficacy of cibenzoline and flecainide for preventing recurrence of atrial arrhythmias was not significantly different (62.5% versus 71.4%). Eleven patients complained of one or more side effects (cibenzoline, n = 6; flecainide, n = 5), justifying leaving the trial in 6 cases (cibenzoline, n = 3; flecainide, n = 3). Two ventricular proarrhythmic effects were observed. No atrial proarrhythmic effects were reported. The efficacy of cibenzoline and flecainide for preventing atrial arrhythmia is good and similar during a follow-up period of 6 months. In view of these results, cibenzoline may be administered first to prevent atrial arrhythmia. PMID:7657846

  8. Perioperative Continuous Ropivacaine Wound Infusion in Laparoscopic Cholecystectomy: A Randomized Controlled Double-blind Trial.

    PubMed

    Fassoulaki, Argyro; Vassi, Emilia; Korkolis, Dimitrios; Zotou, Marianna

    2016-02-01

    Wound infusion with local anesthetics has been used for postoperative pain relief with variable results. This randomized, controlled, double-blind clinical trial examines the effect of ropivacaine infusion on pain after laparoscopic cholecystectomy. A total of 110 patients were randomly assigned to 2 groups. After induction of anesthesia a 75-mm catheter was inserted subcutaneously and connected to an elastomeric pump containing either 0.75% ropivacaine (ropivacaine group) or normal saline (control group) for 24 hours postoperatively. Before skin closure, each hole was infiltrated with 2 mL of 0.75% ropivacaine or normal saline according to randomization. Pain at rest, pain during cough, and analgesic consumption were recorded in the postanesthesia care unit and at 2, 4, 8, 24, and 48 hours postoperatively. Analgesic requirements and pain scores were recorded 1 and 3 months after surgery. The ropivacaine group reported less pain during cough (P=0.044) in the postanesthesia care unit (P=0.017) and 4 hours postoperatively (P=0.038). Ropivacaine wound infusion had no effect on late and chronic pain. PMID:26679680

  9. The Effect of Intravenous Lidocaine on Trigeminal Neuralgia: A Randomized Double Blind Placebo Controlled Trial

    PubMed Central

    Argyra, Erifili

    2014-01-01

    Trigeminal neuralgia is the most common neuralgia. Its therapeutic approach is challenging as the first line treatment often does not help, or even causes intolerable side effects. The aim of our randomized double blind, placebo controlled, crossover study was to investigate in a prospective way the effect of lidocaine in patients with trigeminal neuralgia. Twenty patients met our inclusion criteria and completed the study. Each patient underwent four weekly sessions, two of which were with lidocaine (5 mgs/kg) and two with placebo infusions administered over 60 minutes. Intravenous lidocaine was superior regarding the reduction of the intensity of pain, the allodynia, and the hyperalgesia compared to placebo. Moreover, contrary to placebo, lidocaine managed to maintain its therapeutic results for the first 24 hours after intravenous infusion. Although, intravenous lidocaine is not a first line treatment, when first line medications fail to help, pain specialists may try it as an add-on treatment. This trial is registered with NCT01955967. PMID:27335883

  10. A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts.

    PubMed

    Oliver, D W; Hamilton, S A; Figle, A A; Wood, S H; Lamberty, B G

    2001-12-01

    Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated. PMID:11743409

  11. Efficacy of Trimetazidine Dihydrochloride for Relieving Chronic Tinnitus: A Randomized Double-Blind Study

    PubMed Central

    Kumral, Tolgar Lütfi; Yıldırım, Güven; Berkiten, Güler; Saltürk, Ziya; Ataç, Enes; Atar, Yavuz; Uyar, Yavuz

    2016-01-01

    Objectives: To evaluate the efficacy of trimetazidine dihydrochloride as a treatment for chronic tinnitus. Methods: A total of 97 chronic tinnitus patients were evaluated in this randomized, prospective, double-blind, placebo-controlled trial. After assessing for eligibility, 82 patients were randomly assigned into placebo or trimetazidine groups according to the medication. The trimetazidine group received 20×3 mg/day per oral trimetazidine dihydrochloride and the placebo group received 20×3 mg/day per oral placebo for 3 months. Tinnitus handicap inventory (THI), visual analogue scale (VAS) questionnaires and audiometric results were used to determine the effectiveness of trimetazidine treatment. Results: The study group comprised 82 tinnitus subjects, 42 (51%) of whom received trimetazidine dihydrochloride and 40 (49%) who received placebo. There was no significant difference between placebo and trimetazidine groups in THI grade and VAS (both pre- and posttreatment scores) (P>0.05) and no significant improvement was observed in subjective loudness score in either group (P>0.05). Additionally there was no significant difference between groups in pre- and posttreatment pure tone hearing thresholds at all measured frequencies (P>0.05). Conclusion: Trimetazidine dihydrochloride therapy was ineffective for relieving chronic tinnitus. PMID:27230273

  12. Soy Isoflavones Supplementation for Patients with Irritable Bowel Syndrome: A Randomized Double Blind Clinical Trial

    PubMed Central

    Jalili, Mahsa; Vahedi, Homayoon; Janani, Leila; Poustchi, Hossein; Malekzadeh, Reza; Hekmatdoost, Azita

    2015-01-01

    BACKGROUND Irritable bowel syndrome (IBS) is one of the common gastrointestinal disorders with unknown etiology. In experimental models, it is proposed that soy isoflavones may suppress the clinical and psychological symptoms of IBS by alteration of gut barrier tight junctions. METHODS We conducted this study to evaluate the effects of soy isoflavones on IBS symptoms and patients’ quality of life. In a randomized double blind placebo-controlled clinical trial, 67 patients with IBS were allocated to consume either soy isoflavones capsules or a placebo for 6 weeks. The primary outcome was a significant reduction in symptoms severity score and the secondary outcome was a significant improvement in quality of life. RESULTS 45 participants completed the study. There was no significant changes in mean differences of symptoms severity score between the two groups; however soy isoflavone supplementation could significantly improve the quality of life scores (p=0.009). CONCLUSION Soy isoflavones supplementation could improve the quality of life in patients with IBS; however it did not suppress the symptoms severity in 6 weeks. Further research with a longer duration is needed to determine the sustained clinical efficacy. This study was registered at clinicaltrials.gov as NCT02026518 PMID:26396720

  13. Etizolam in the treatment of generalized anxiety disorder: a double-blind study versus placebo.

    PubMed

    Casacchia, M; Bolino, F; Ecari, U

    1990-01-01

    A double-blind, placebo-controlled study was carried out in 36 patients diagnosed as suffering from Generalized Anxiety Disorder with associated depressive symptoms to assess the efficacy and tolerability of two unitary doses of etizolam. After a 1-week wash-out period on placebo, patients were assigned at random to receive 1 tablet twice daily of either 0.50 mg or 0.25 mg etizolam or placebo for 5 weeks. Assessments were made at entry, on Day 21 and Day 35 of the patients' condition and symptoms using a battery of four psychometric tests (the Hamilton rating scales for anxiety and for depression, the Covi scale for anxiety and the Raskin scale for depression). Ten patients were withdrawn before the end of the study, 8 because of inadequate response (4 on placebo, 3 on 0.25 mg etizolam and 1 on 0.50 mg etizolam) in spite of dosage increase to 1 tablet 3-times daily, and 2 because of side-effects (both on 0.50 mg etizolam). Analysis of the results from the remaining 26 patients showed that, at the 0.50 mg dosage level, etizolam produced significant improvement in anxiety and depressive symptoms, particularly somatic manifestations, and was significantly more effective than placebo or the 0.25 dosage regimen. Etizolam was generally well tolerated and the few side-effects reported, mainly daytime drowsiness, were of mild to moderate severity. PMID:1981698

  14. A double blind randomized controlled trial of Maharishi Vedic vibration technology in subjects with arthritis.

    PubMed

    Nader, T A; Smith, D E; Dillbeck, M C; Schanbacher, V; Dillbeck, S L; Gallois, P; Beall-Rougerie, S; Schneider, R H; Nidich, S I; Kaplan, G P; Belok, S

    2001-04-01

    To explore ancient Vedic medical techniques, one hundred and seventy-six subjects with arthritis participated in a controlled study through the non-pharmacologic approach known as the Maharishi Vedic Vibration Technology (MVVT). Using a double-blinded and randomized experimental design, the findings showed significant reductions of pain and stiffness, and improvement in range of motion in the study sample. One hundred percent relief of symptoms was the most commonly reported category of improvement due to treatment. For the group as a whole, differences in mean response of treatment and control conditions with respect to relief of pain, limitation of motion, and reduction in stiffness were highly significant: t values ranged from a low of 5.609 in stiffness to a high of 20.950 in pain, p = 0.000009 to <10-49 respectively. Analysis by sub-categories of peripheral arthritis, painful conditions of the spine, and rheumatoid arthritis likewise produced significant results. Mechanisms of action were proposed, drawing on Maharishi Vedic Science, developments in quantum field theory, and specifically the theories of chaos and self-organizing systems as they relate to physiological functioning. The instantaneous relief of pain and improvement in function in such a high proportion of subjects with chronic arthritis is unparalleled in modern medical science PMID:11282569

  15. Prophylaxis of traveler's diarrhea in Egypt: results of a double blind controlled study.

    PubMed

    Raedsch, R; Walter-Sack, I; Galle, P R; Kommerell, B

    1991-11-26

    Diarrhea represents the most frequent health problem of Western tourists visiting subtropical and tropical areas. Antibiotic prophylaxis has been suggested by some authors but may not be generally advisable because of adverse drug effects. In the present study we investigated the prophylaxis of traveler's diarrhea using a combination of tannalbuminate and ethacridin-lactate. During a 16-day cruise in Egypt, 77 tourists were assigned to either placebo or prophylactic doses of tannalbuminate (500 mg) and ethacridin-lactate (50 mg), 1 tbl. b.i.d., in a randomized double-blind fashion. The number of bowel movements, consistency of stools, and clinical symptoms like nausea, abdominal cramps, vomiting, and fever were monitored daily. In the placebo group (n = 43) 35 tourists developed diarrhea (81.4%), whereas in the verum group (n = 34) only 18 tourists (52.9%) had diarrhea (p less than 0.0125). In the travelers receiving verum and developing diarrhea the clinical symptoms were less pronounced than in the placebo group. These results demonstrate that the events of traveler's diarrhea may be reduced; moreover, symptoms are attenuated by medical prophylaxis with tannalbuminate and ethacridin-lactate. PMID:1812314

  16. Metoprolol and propranolol in essential tremor: a double-blind, controlled study.

    PubMed Central

    Calzetti, S; Findley, L J; Gresty, M A; Perucca, E; Richens, A

    1981-01-01

    Single oral doses of propranolol (120 mg), metoprolol (150 mg) and placebo were given in a randomised, double-blind fashion to 23 patients with essential tremor. Both beta blockers were significantly more effective than placebo in reducing the magnitude of tremor. The decrease in tremor produced by metoprolol (47, sem 9%, n = 23) was not significantly different from that observed propranolol (55, sem 5%, n = 23). Tachycardia on standing was antagonised by both drugs to a similar extent. These findings suggest that metoprolol may represent a valuable alternative to propranolol in the treatment of essential tremor. The data is consistent with the hypothesis that the tremorolytic effect of beta blockers in these patients may be unrelated to peripheral beta-2 adreno-receptor blockade, being possibly mediated by other central or peripheral modes of action of these drugs. However, it cannot be excluded that at the dose used, metoprolol had lost its relative cardio-selectivity and that the reduction in tremor was mediated by competitive antagonism at beta-2 receptor sites in skeletal muscle. PMID:7031187

  17. Rhus Coriaria L. (Sumac) in Patients with Hyperlipidemia; A Double Blind Randomized Clinical Trial

    PubMed Central

    Hajmohammadi, Zahra; Shams, Mesbah; Zibainejad, Mohammad Javad; Nimrouzi, Majid; Fardidi, Pouya; Heydari, Mojtaba

    2016-01-01

    Background: Lipid lowering effect of sumac is investigated in multiple animal studies with promising results. However, its clinical efficacy is not investigated adequately. This study is aimed to evaluate the lipid lowering effect of sumac in patients with Hyperlipidemia in a double blind randomized controlled trial. Methods: Eighty patients with Hyperlipidemia according to NCEP-ATP III criteria were randomly allocated to receive the Rhus Coriaria L. (1000 mg/day) or placebo for two months. The patients were evaluated in terms of the serum triglyceride, total LDL, and HDL cholesterol. Systolic and diastolic blood pressures along with serum biochemistry profile including fasting blood sugar, liver and kidney function tests and complete blood count were evaluated before the enrolment of patients and after the intervention. Results: No significant difference was observed between the sumac and placebo groups in term of mean reductions in total and LDL cholesterol and triglyceride levels. A significant increase in mean serum HDL cholesterol level was observed in the sumac group (41.18±8.2 vs. 44.65±8.4, P=0.001) after 2 months of intervention. Conclusion: The study showed significant HDL cholesterol increasing effect of sumac supplementation in patients with Hyperlipidemia.

  18. Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy

    SciTech Connect

    Prummel, M.F.; Mourits, M.; Blank, L.; Berghout, A.; Koornneef, L.; Wiersinga, W.M. )

    1993-10-16

    Corticosteriods are usually given for management of Graves' ophthalmopathy, but they have many and serious side-effects. By comparison, retrobulbar irradiation is well tolerated, although its efficacy has been evaluated only in uncontrolled studies. Therefore, the authors did a double-blind randomized trial, in which 28 patients with moderately severe Graves' ophthalmopathy were treated with a 3-month course of oral prednisone and sham irradiation, and 28 received retrobulbar irradiation (20 Gy) and placebo capsules. Therapeutic outcome, assessed twenty-four weeks after the start of treatment, was determined by the change in the highest NOSPECS class. A successful outcome was observed in 14 prednisone-treated and in 13 irradiated patients. Responders to treatment (but not nonresponders) in both groups showed improvements in total and subjective eye score and a decrease in eye-muscle volume. Response to either treatment was due largely to changes in soft-tissue involvement and eye-muscle motility. Radiotherapy and oral prednisone appear to be equally effective as initial treatment in patients with moderately severe Graves' ophthalmopathy. In view of its better tolerability, radiotherapy should be considered the treatment of first choice.

  19. The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

    PubMed Central

    Pickering, Gisèle; Kastler, Adrian; Macian, Nicolas; Pereira, Bruno; Valabrègue, Romain; Lehericy, Stéphane; Boyer, Louis; Dubray, Claude; Jean, Betty

    2015-01-01

    Background Paracetamol’s (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans. Methods and results This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter. Conclusion These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain. PMID:26229445

  20. Lansoprazole for long-term maintenance therapy of erosive esophagitis: double-blind comparison with ranitidine.

    PubMed

    Peura, David A; Freston, James W; Haber, Marian M; Kovacs, Thomas O; Hunt, Barbara; Atkinson, Stuart

    2009-05-01

    In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P<0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P<0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P<0.001). Symptom status correlated with healing (P=0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief. PMID:18726153

  1. Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field study.

    PubMed

    Taylor, Marcus K; Padilla, Genieleah A; Stanfill, Katherine E; Markham, Amanda E; Khosravi, Jasmine Y; Ward, Michael D Dial; Koehler, Matthew M

    2012-01-01

    Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are anabolic prehormones involved in the synthesis of testosterone. Both have been shown to exert neuroprotective effects during stress. In this randomized, controlled, double-blind field study, we examined the effects of a 12-day DHEA regimen on stress indices in military men undergoing survival training. Forty-eight men were randomized to either a DHEA treatment group or placebo control group. The treatment group received 50 mg of oral DHEA supplementation daily for 5 days during classroom training followed by 7 days of 75 mg during stressful field operations. Control subjects received identical placebo pills. Salivary assays (DHEA[S], testosterone, and cortisol) were conducted at four time points: distal pre-stress (T1), proximal pre-stress (T2), mock-captivity stress (T3), and 24 h recovery (T4). Subjective distress was also assessed at T1, T3, and T4. As expected, DHEA treatment resulted in higher salivary concentrations of DHEA and DHEAS during daily living, mock-captivity stress, and recovery. Similar patterns were observed for salivary markers of anabolic balance: DHEA/cortisol, DHEAS/cortisol, and testosterone/cortisol concentration ratios. Despite notable time effects, no group differences emerged for subjective distress. A brief, low dose DHEA regimen yielded large increases in salivary DHEA(S) concentrations and enhanced anabolic balance throughout sustained military stress. These physiological changes did not extrapolate to subjective distress. PMID:21790446

  2. 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

  3. Efficacy of transforaminal versus interspinous corticosteroid injectionin discal radiculalgia - a prospective, randomised, double-blind study.

    PubMed

    Thomas, E; Cyteval, C; Abiad, L; Picot, M C; Taourel, P; Blotman, F

    2003-10-01

    A prospective, randomised, double-blind study was carried out to compare the respective efficacies of transforaminal and interspinous epidural corticosteroid injections in discal radiculalgia. Thirty-one patients (18 females, 13 males) with discal radicular pain of less than 3 months' duration were consecutively randomised to receive either radio-guided transforaminal or blindly performed interspinous epidural corticosteroid injections. Post-treatment outcome was evaluated clinically at 6 and 30 days, and then at 6 months, but only by mailed questionnaire. At day 6, the between-group difference was significantly in favour of the transforaminal group with respect to Schober's index, finger-to-floor distance, daily activities, and work and leisure activities on the Dallas pain scale. At day 30, pain relief was significantly better in the transforaminal group. At month 6, answers to the mailed questionnaire still showed significantly better results for transforaminal injection concerning pain, daily activities, work and leisure activities and anxiety and depression, with a decline in the Roland-Morris score. In recent discal radiculalgia, the efficacy of radio-guided transforaminal epidural corticosteroid injections was higher than that obtained with blindly-performed interspinous injections. PMID:14579160

  4. Managing tissue heating in laser therapy to enable double-blind clinical study

    NASA Astrophysics Data System (ADS)

    Catanzaro, Brian; de Taboada, Luis; Streeter, Jackson

    2006-02-01

    Laser devices in clinical applications must eventually be tested via clinical trials. An essential component in clinical trials is the double-blind study whereby the patient and the treating physician have no knowledge as to whether a given treatment is active or placebo. In pharmaceuticals, the problem is easily addressed. With laser therapy this can be very challenging. For some optical therapies, laser heating of tissue, by even as little as a few degrees can indicate to the patient and/or the physician that the device is active, un-blinding the study. This problem has been analyzed for a specific laser therapy using a combination of clinical data, analytical methods, finite element modeling, and laboratory testing. The methods used arrived at a solution, but not necessarily one that could have been predicted easily. This paper will present a model of tissue heating and the methods used to mask the effects from the laser in an effort to make active treatment and placebo indistinguishable.

  5. Static magnetic therapy does not decrease pain or opioid requirements: a randomized double-blind trial.

    PubMed

    Cepeda, M Soledad; Carr, Daniel B; Sarquis, Tony; Miranda, Nelcy; Garcia, Ricardo J; Zarate, Camilo

    2007-02-01

    A growing multibillion dollar industry markets magnetic necklaces, bracelets, bands, insoles, back braces, mattresses, etc., for pain relief, although there is little evidence for their efficacy. We sought to evaluate the effect of magnetic therapy on pain intensity and opioid requirements in patients with postoperative pain. We designed a randomized, double-blind, controlled trial. One-hundred-sixty-five patients older than 12 yr of age were randomized to magnetic (n = 81) or sham therapy (n = 84) upon reporting moderate-to-severe pain in the postanesthesia care unit. Devices were placed over the surgical incision and left in place for 2 h. Patients rated their pain intensity on a 0-10 scale every 10 min and received incremental doses of morphine until pain intensity was < or =4 of 10. Pain intensity levels were similar in both groups. The magnet group had on average 0.04 U more pain intensity (95% confidence interval, -0.4 to 0.5) than the sham group. Opioid requirements also were similar in both groups. The active magnet group required 1.5 mg more morphine (95% confidence interval, -1.8 to 4.0) than the sham magnet group. Magnetic therapy lacks efficacy in controlling acute postoperative pain intensity levels or opioid requirements and should not be recommended for pain relief in this setting. PMID:17242082

  6. Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial.

    PubMed

    Rawal, Narinder; Macquaire, Valery; Catalá, Elena; Berti, Marco; Costa, Rui; Wietlisbach, Markus

    2011-01-01

    This randomized, double-blind, double-dummy, multicenter trial compared efficacy and safety of tramadol HCL 37.5 mg/paracetamol 325 mg combination tablet with tramadol HCL 50 mg capsule in the treatment of postoperative pain following ambulatory hand surgery with iv regional anesthesia. Patients received trial medication at admission, immediately after surgery, and every 6 hours after discharge until midnight of the first postoperative day. Analgesic efficacy was assessed by patients (n = 128 in each group, full analysis set) and recorded in a diary on the evening of surgery day and of the first postoperative day. They also documented the occurrence of adverse events. By the end of the first postoperative day, the proportion of treatment responders based on treatment satisfaction (primary efficacy variable) was comparable between the groups (78.1% combination, 71.9% tramadol; P = 0.24) and mean pain intensity (rated on a numerical scale from 0 = no pain to 10 = worst imaginable pain) had been reduced to 1.7 ± 2.0 for both groups. Under both treatments, twice as many patients experienced no pain (score = 0) on the first postoperative day compared to the day of surgery (35.9% vs 16.4% for tramadol/paracetamol and 36.7% vs 18% for tramadol treatment). Rescue medication leading to withdrawal (diclofenac 50 mg) was required by 17.2% patients with tramadol/paracetamol and 13.3% with tramadol. Adverse events (mainly nausea, dizziness, somnolence, vomiting, and increased sweating) occurred less frequently in patients under combination treatment (P = 0.004). Tramadol/paracetamol combination tablets provided comparable analgesic efficacy with a better safety profile to tramadol capsules in patients experiencing postoperative pain following ambulatory hand surgery. PMID:21559356

  7. Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin.

    PubMed

    Engelmann, Udo; Walther, Carola; Bondarenko, Boris; Funk, Petra; Schläfke, Sandra

    2006-01-01

    The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH. PMID:16618015

  8. 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

  9. 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

  10. 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

  11. Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness.

    PubMed

    Cohen, Steven P; Peterlin, B Lee; Fulton, Larry; Neely, Edward T; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C; Jacobs, Michael B; Plunkett, Anthony R; Verdun, Aubrey J; Stojanovic, Milan P; Hanling, Steven; Constantinescu, Octav; White, Ronald L; McLean, Brian C; Pasquina, Paul F; Zhao, Zirong

    2015-12-01

    Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline -2.743 ± 2.487 vs -1.377 ± 1.970; P < 0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline -1.925 ± 3.204 vs -0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline -2.738 ± 2.753 vs -1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures. PMID:26447705

  12. A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain.

    PubMed

    Rowbotham, Michael C; Duan, W Rachel; Thomas, James; Nothaft, Wolfram; Backonja, Misha-Miroslav

    2009-12-01

    ABT-594 is a neuronal nicotinic acetylcholine receptor (NNR) agonist that exhibits potent analgesic activity in preclinical models of acute, chronic, and neuropathic pain. The purpose of this phase 2, randomized, multicenter, double-blind, placebo-controlled study was to evaluate the safety and analgesic efficacy of ABT-594 in patients with diabetic peripheral neuropathic pain (DPNP). A total of 266 DPNP patients were randomized 1:1:1:1 to receive placebo, ABT-594 150 microg BID, ABT-594 225 microg BID, or ABT-594 300 microg BID. Patients were titrated to a fixed-dose of ABT-594 over 7 days and remained at this dose for another 6 weeks. Compared to placebo, all three ABT-594 treatment groups showed significantly greater decreases on the average diary-based 0-10 Pain Rating Scale (PRS) score from baseline to final evaluation, the primary efficacy measure (placebo, -1.1; 150 microg BID, -1.9; 225 microg BID, -1.9; 300 microg BID, -2.0). The proportion of patients achieving at least a 50% improvement in the average diary-based PRS was greater in all three ABT-594 treatment groups. However, adverse event (AE) dropout rates were significantly higher in all three ABT-594 treatment groups (28% for 150 microg BID, 46% for 225 microg BID, and 66% for 300 microg BID) than for the placebo group (9%). Consistent with the expected side-effect profile of NNR agonists, the most frequently reported AEs were nausea, dizziness, vomiting, abnormal dreams, and asthenia. This study establishes proof of concept for NNR agonists as a new class of compounds for treating neuropathic pain. PMID:19632048

  13. 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

  14. A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia.

    PubMed

    Le Bars, P L; Kieser, M; Itil, K Z

    2000-01-01

    This intent-to-treat (ITT) analysis was performed to provide a realistic image of the efficacy that could be expected after 26 weeks treatment with a 120-mg dose (40 mg t.i.d.) of EGb 761 (EGb). The data were collected during a 52-week, double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study. Patients were mildly to severely impaired and diagnosed with uncomplicated Alzheimer's disease or multi-infarct dementia according to ICD-10 and DSM-III-R criteria. The primary outcome measures included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Geriatric Evaluation by Relative's Rating Instrument (GERRI) and Clinical Global Impression of Change. From 309 patients included in the ITT analysis, 244 patients (76% for placebo and 73% for EGb) actually reached the 26th week visit. In comparison to the baseline values, the placebo group showed a statistically significant worsening in all domains of assessment, while the group receiving EGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS-Cog (p = 0.04) and the GERRI (p = 0.007). In the group receiving EGb, 26% of the patients achieved at least a 4-point improvement on the ADAS-Cog, compared to 17% with placebo (p = 0.04). On the GERRI, 30% of the EGb group improved and 17% worsened, while the placebo group showed an opposite trend with 37% of patients worsening for 25% improved (p = 0.006). Regarding safety, no differences between EGb and placebo were observed. PMID:10867450

  15. A randomized double-blind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain

    PubMed Central

    Ziegler, Dan; Duan, W. Rachel; An, Guohua; Thomas, James W.; Nothaft, Wolfram

    2015-01-01

    Abstract T-type Cav3.2 calcium channels represent a novel target for neuropathic pain modulation. Preclinical studies with ABT-639, a peripherally acting highly selective T-type Cav3.2 calcium channel blocker, showed dose-dependent reduction of pain in multiple pain models. ABT-639 also demonstrated an acceptable safety profile at single- and multiple-dose levels evaluated in a clinical phase 1 study in healthy volunteers. The primary objective of this phase 2, multicenter, randomized, double-blind, placebo-controlled, and active-controlled study was to compare the analgesic efficacy and safety of ABT-639 with placebo in the treatment of diabetic neuropathic pain. Pregabalin, an approved treatment for painful diabetic neuropathy, was included as a positive control. A total of 194 patients were randomized and treated for 6 weeks; 62 patients received ABT-639 (100 mg twice daily), 70 patients received pregabalin (150 mg twice daily), and 62 patients received placebo. When assessing the mean changes from baseline in patient-recorded pain scores at the end of week 6, there was no significant difference observed for ABT-639 compared with placebo (−2.28 vs −2.36; P = 0.582). Pregabalin treatment resulted in a transient improvement in pain compared with placebo, which did not persist throughout the study. There were no significant safety issues identified with ABT-639. A majority of adverse events were considered mild to moderate in intensity. In conclusion, treatment with the highly selective T-type Cav3.2 calcium channel blocker ABT-639 100 mg twice daily for 6 weeks showed no safety signals that would preclude further investigation but did not reduce neuropathic pain in patients with diabetes (ClinicalTrials.gov identifier: NCT01345045). PMID:26067585

  16. 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

  17. Therapeutic value of a Lactobacillus gasseri and Bifidobacterium longum fixed bacterium combination in acute diarrhea: a randomized, double-blind, controlled clinical trial.

    PubMed

    Margreiter, M; Ludl, K; Phleps, W; Kaehler, S T

    2006-05-01

    A multicenter, parallel-group, randomized, double-blind, active-controlled clinical trial, involving 169 outpatients at 9 centers, was conducted to assess the efficacy of a fixed bacterium combination of Lactobacillus gasseri and Bifidobacterium longum in the therapy of acute diarrhea. In particular, this clinical trial was designed to prove equivalent therapeutic efficacy of a fixed bacterium combination versus an exhaustive investigated mono-bacterium medicinal product. All patients, free to carry on usual daily activities, received 1 capsule 3 times a day of either a fixed bacterium combination of Lactobacillus gasseri and Bifidobacterium longum or Enterococcus faecium mono-bacterium. All treatments were continued for a maximum of 6 days in line with the normal course of acute diarrhea. Primary efficacy criterion was the severity and duration of diarrhea assessed by the ensemble of stool frequency as change from baseline and stool consistency at trial Day 2, 3 and 4, and time in days until normal bowel function (recovery). The median duration of diarrhea was 2.70 days versus 2.67 days (fixed bacterium combination of Lactobacillus gasseri and Bifidobacterium longum versus mono-bacterium Enterococcus feacium). The total mean difference of duration of diarrhea was 0.072 days. This result can be considered equivalent. However, the proportion of patients with complete recovery tended to be higher in the fixed bacterium combination group (92.6% versus 87.1%) resulting in a number needed to treat (NNT) of 18.1. The fixed bacterium combination reduced the number of unformed stools by 80% and the mono-bacterium by 75% during the first 2 days of treatment. Both treatments were well tolerated. Oral therapy with a fixed combination of Lactobacillus gasseri and Bifidobacterium longum shortens the duration and decreases the severity of acute self-limiting diarrhea in adults comparable to an effective mono-bacterium medicinal product. It therefore appears to be a useful and

  18. Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness

    PubMed Central

    Cohen, Steven P.; Peterlin, B. Lee; Fulton, Larry; Neely, Edward T.; Kurihara, Connie; Gupta, Anita; Mali, Jimmy; Fu, Diana C.; Jacobs, Michael B.; Plunkett, Anthony R.; Verdun, Aubrey J.; Stojanovic, Milan P.; Hanling, Steven; Constantinescu, Octav; White, Ronald L.; McLean, Brian C.; Pasquina, Paul F.; Zhao, Zirong

    2015-01-01

    Occipital neuralgia (ON) is characterized by lancinating pain and tenderness overlying the occipital nerves. Both steroid injections and pulsed radiofrequency (PRF) are used to treat ON, but few clinical trials have evaluated efficacy, and no study has compared treatments. We performed a multicenter, randomized, double-blind, comparative-effectiveness study in 81 participants with ON or migraine with occipital nerve tenderness whose aim was to determine which treatment is superior. Forty-two participants were randomized to receive local anesthetic and saline, and three 120 second cycles of PRF per targeted nerve, and 39 were randomized to receive local anesthetic mixed with deposteroid and 3 rounds of sham PRF. Patients, treating physicians, and evaluators were blinded to interventions. The PRF group experienced a greater reduction in the primary outcome measure, average occipital pain at 6 weeks (mean change from baseline −2.743 ± 2.487 vs −1.377 ± 1.970; P <0.001), than the steroid group, which persisted through the 6-month follow-up. Comparable benefits favoring PRF were obtained for worst occipital pain through 3 months (mean change from baseline−1.925 ± 3.204 vs−0.541 ± 2.644; P = 0.043), and average overall headache pain through 6 weeks (mean change from baseline −2.738 ± 2.753 vs −1.120 ± 2.1; P = 0.037). Adverse events were similar between groups, and few significant differences were noted for nonpain outcomes. We conclude that although PRF can provide greater pain relief for ON and migraine with occipital nerve tenderness than steroid injections, the superior analgesia may not be accompanied by comparable improvement on other outcome measures. PMID:26447705

  19. The Explorer study: the first double-blind RCT to assess the efficacy of TLC-NOSF on DFUs.

    PubMed

    Shanahan, D R

    2013-02-01

    Urgo Medical recently announced the launch of the Explorer study, a large, Europe-wide, clinical study on the efficacy and tolerability of UrgoStart Contact, a lipidocolloid technology dressing impregnated with nano-oligosaccharide factor, in the treatment of diabetic foot ulceration. The number of patients, investigating centres and countries involved, as well as the length of treatment and patient follow-up, make this an ambitious, double-blind, randomised controlled trial. PMID:23665662

  20. Dexmedetomidine as an adjunct in postoperative analgesia following cardiac surgery: A randomized, double-blind study

    PubMed Central

    Priye, Shio; Jagannath, Sathyanarayan; Singh, Dipali; Shivaprakash, S.; Reddy, Durga Prasad

    2015-01-01

    Objectives: The purpose of this study was to determine analgesic efficacy of dexmedetomidine used as a continuous infusion without loading dose in postcardiac surgery patients. Settings and Design: A prospective, randomized, double-blind clinical study in a single tertiary care hospital on patients posted for elective cardiac surgery under cardiopulmonary bypass. Interventions: Sixty-four patients who underwent elective cardiac surgery under general anesthesia were shifted to intensive care unit (ICU) and randomly divided into two groups. Group A (n = 32) received a 12 h infusion of normal saline and group B (n = 32) received a 12 h infusion of dexmedetomidine 0.4 μg/kg/h. Postoperative pain was managed with bolus intravenous fentanyl. Total fentanyl consumption, hemodynamic monitoring, Visual Analogue Scale (VAS) pain ratings, Ramsay Sedation Scale were charted every 6th hourly for 24 h postoperatively and followed-up till recovery from ICU. Student's t-test, Chi-square/Fisher's exact test has been used to find the significance of study parameters between the groups. Results: Dexmedetomidine treated patients had significantly less VAS score at each level (P < 0.001). Total fentanyl consumption in dexmedetomidine group was 128.13 ± 35.78 μg versus 201.56 ± 36.99 μg in saline group (P < 0.001). A statistically significant but clinically unimportant sedation was noted at 6 and 12 h (P < 0.001, and P = 0.046 respectively). Incidence of delirium was less in dexmedetomidine group (P = 0.086+). Hemodynamic parameters were statistically insignificant. Conclusions: Dexmedetomidine infusion even without loading dose provides safe, effective adjunct analgesia, reduces narcotic consumption, and showed a reduced trend of delirium incidence without undesirable hemodynamic effects in the cardiac surgery patients. PMID:26543448

  1. Varenicline Effects on Smoking, Cognition, and Psychiatric Symptoms in Schizophrenia: A Double-Blind Randomized Trial

    PubMed Central

    Si, Tian-Mei; Maayan, Lawrence; Jin, Hua; Boules, Sylvia; Sershen, Henry; Li, Chunbo; Ren, Juanjuan; Liu, Yanhong; Youseff, Mary; Lajtha, Abel; Guidotti, Alessandro; Weiser, Mark; Davis, John M.

    2016-01-01

    Schizophrenic patients have a high rate of smoking and cognitive deficits which may be related to a decreased number or responsiveness of nicotinic receptors in their brains. Varenicline is a partial nicotinic agonist which is effective as an antismoking drug in cigarette smokers, although concerns have been raised about potential psychiatric side-effects. We conducted a double-blind placebo controlled study in 87 schizophrenic smokers to evaluate the effects of varenicline (2 mg/day) on measures of smoking, cognition, psychiatric symptoms, and side-effects in schizophrenic patients who were cigarette smokers. Varenicline significantly decreased cotinine levels (P<0.001), and other objective and subjective measures of smoking (P < .01), and responses on a smoking urges scale (P = .02), more than placebo. Varenicline did not improve scores on a cognitive battery designed to test the effect of drugs on cognitive performance in schizophrenia (the MATRICS battery), either in overall MATRICS battery Composite or individual Domain scores, more than placebo. There were no significant differences between varenicline vs. placebo effects on total symptom scores on psychiatric rating scales, PANSS, SANS, or Calgary Depression scales, and there were no significant drug effects in any of these scales sub-scores when we used Benjamin-Hochberg corrected significance levels (α = .05). Varenicline patients did not show greater side-effects than placebo treated patients at any time point when controlled for baseline side-effect scores. Our study supports the use of varenicline as a safe drug for smoking reduction in schizophrenia but not as a cognitive enhancer. Trial Registration: ClinicalTrials.gov 00802919 PMID:26730716

  2. Prevention of postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomised double blind multicentre trial

    PubMed Central

    Wallenborn, Jan; Gelbrich, Götz; Bulst, Detlef; Behrends, Katrin; Wallenborn, Hasso; Rohrbach, Andrea; Krause, Uwe; Kühnast, Thomas; Wiegel, Martin; Olthoff, Derk

    2006-01-01

    Objectives To determine whether 10 mg, 25 mg, or 50 mg metoclopramide combined with 8 mg dexamethasone, given intraoperatively, is more effective in preventing postoperative nausea and vomiting than 8 mg dexamethasone alone, and to assess benefit in relation to adverse drug reactions. Design Four-armed, parallel group, double blind, randomised controlled clinical trial. Setting Four clinics of a university hospital and four district hospitals in Germany. Participants 3140 patients who received balanced or regional anaesthesia during surgery. Main outcome measures Postoperative nausea and vomiting within 24 hours of surgery (primary end point); occurrence of adverse reactions. Results Cumulative incidences (95% confidence intervals) of postoperative nausea and vomiting were 23.1% (20.2% to 26.0%), 20.6% (17.8% to 23.4%), 17.2% (14.6% to 19.8%), and 14.5% (12.0% to 17.0%) for 0 mg, 10 mg, 25 mg, and 50 mg metoclopramide. In the secondary analysis, 25 mg and 50 mg metoclopramide were equally effective at preventing early nausea (0-12 hours), but only 50 mg reduced late nausea and vomiting (> 12 hours). The most frequent adverse drug reactions were hypotension and tachycardia, with cumulative incidences of 8.8% (6.8% to 10.8%), 11.2% (9.0% to 13.4%), 12.9% (10.5% to 15.3%), and 17.9% (15.2% to 20.6%) for 0 mg, 10 mg, 25 mg, and 50 mg metoclopramide. Conclusion The addition of 50 mg metoclopramide to 8 mg dexamethasone (given intraoperatively) is an effective, safe, and cheap way to prevent postoperative nausea and vomiting. A reduced dose of 25 mg metoclopramide intraoperatively, with additional postoperative prophylaxis in high risk patients, may be equally effective and cause fewer adverse drug reactions. Trial registration Current Controlled Trials ISRCTN31625370. PMID:16861255

  3. A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome.

    PubMed

    Einfeld, Stewart L; Smith, Ellie; McGregor, Iain S; Steinbeck, Kate; Taffe, John; Rice, Lauren J; Horstead, Siân K; Rogers, Naomi; Hodge, M Antoinette; Guastella, Adam J

    2014-09-01

    Individuals with Prader-Willi syndrome (PWS) have a significant reduction in the number of oxytocin-producing neurons (42%) in the hypothalamic paraventricular nucleus. A number of animal studies and observations of humans show that lesions in this region can produce PWS-like symptoms. Given the evidence for potential oxytocin deficiency, we tested the effects of a course of intranasal oxytocin on PWS symptoms. Thirty individuals with PWS aged 12-30 years participated in an 18-week randomized double-blind placebo-controlled crossover trial. Participants received 8 weeks of oxytocin and 8 weeks of placebo with a minimum 2-week washout period. The first 11 participants received the following oxytocin doses: 24 IU (twice daily) B.I.D for participants 16 years and over and 18 IU B.I.D for participants 13-15 years. The dose was increased for the remaining 18 participants to 40 IU B.I.D for participants 16 years and over and 32 IU B.I.D for 13-15 years. Measures used to assess changes were standardized well-accepted measures, including the Developmental Behavior Checklist-Monitor, Parent, Teacher, and Adult; The Yale-Brown Obsessive Compulsive Scale; The Dykens Hyperphagia questionnaire; Reading The Mind in the Eyes Test; Epworth Sleepiness Scale and the Movie Stills. Oxytocin had little impact on any measure. The only significant difference found between the baseline, oxytocin, and placebo measures was an increase in temper outbursts (P = 0.023) with higher dose oxytocin. The lack of effect of oxytocin nasal spray may reflect the importance of endogenous release of oxytocin in response to exogenous oxytocin. PMID:24980612

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

    PubMed Central

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

    2011-01-01

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

  5. Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial

    PubMed Central

    Buigues, Cristina; Fernández-Garrido, Julio; Pruimboom, Leo; Hoogland, Aldert J.; Navarro-Martínez, Rut; Martínez-Martínez, Mary; Verdejo, Yolanda; Mascarós, Mari Carmen; Peris, Carlos; Cauli, Omar

    2016-01-01

    Aging can result in major changes in the composition and metabolic activities of bacterial populations in the gastrointestinal system and result in impaired function of the immune system. We assessed the efficacy of prebiotic Darmocare Pre® (Bonusan Besloten Vennootschap (BV), Numansdorp, The Netherlands) to evaluate whether the regular intake of this product can improve frailty criteria, functional status and response of the immune system in elderly people affected by the frailty syndrome. The study was a placebo-controlled, randomized, double blind design in sixty older participants aged 65 and over. The prebiotic product was composed of a mixture of inulin plus fructooligosaccharides and was compared with placebo (maltodextrin). Participants were randomized to a parallel group intervention of 13 weeks’ duration with a daily intake of Darmocare Pre® or placebo. Either prebiotic or placebo were administered after breakfast (between 9–10 a.m.) dissolved in a glass of water carefully stirred just before drinking. The primary outcome was to study the effect on frailty syndrome. The secondary outcomes were effect on functional and cognitive behavior and sleep quality. Moreover, we evaluated whether prebiotic administration alters blood parameters (haemogram and biochemical analysis). The overall rate of frailty was not significantly modified by Darmocare Pre® administration. Nevertheless, prebiotic administration compared with placebo significantly improved two frailty criteria, e.g., exhaustion and handgrip strength (p < 0.01 and p < 0.05, respectively). No significant effects were observed in functional and cognitive behavior or sleep quality. The use of novel therapeutic approaches influencing the gut microbiota–muscle–brain axis could be considered for treatment of the frailty syndrome. PMID:27314331

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

    PubMed Central

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

    2013-01-01

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

  7. Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine.

    PubMed

    Kreinin, Anatoly; Miodownik, Chanoch; Mirkin, Vitaly; Gaiduk, Yulia; Yankovsky, Yan; Bersudsky, Yuly; Lerner, Paul P; Bergman, Joseph; Lerner, Vladimir

    2016-06-01

    Hypersalivation is a frequent, disturbing, and uncomfortable adverse effect of clozapine therapy that frequently leads to noncompliance. The aim of this study was to examine the efficacy of metoclopramide (dopamine D2 antagonist, antiemetic medication) as an option for management of hypersalivation associated with clozapine (HAC). A 3-week, double-blind, placebo-controlled trial was conducted in university-based research clinics from January 2012 to May 2014, on 58 inpatients treated with clozapine who were experiencing hypersalivation. The subjects were randomly divided into placebo and metoclopramide groups. The starting dose was 10 mg/d. Participants who did not respond were up-titrated 10 mg/d weekly to a total of 30 mg/d during the third week. The number of placebo capsules was increased accordingly up to 3 capsules per day. Primary outcome was the change from baseline to the end of study in the severity of hypersalivation as measured with the Nocturnal Hypersalivation Rating Scale and the Drooling Severity Scale. Secondary outcomes included Clinical Global Impression of Improvement scale and adverse effect scales. Significant improvement on the Nocturnal Hypersalivation Rating Scale was demonstrated in the metoclopramide group from the end of the second week (P < 0.004), and on the Drooling Severity Scale (P < 0.02) in the third week. Clinical Global Impression-Improvement scale scores revealed major improvement. Twenty subjects (66.7%) treated with metoclopramide reported significant decline or total disappearance of HAC in comparison to 8 patients (28.6%) who received placebo (P = 0.031). No adverse effects to metoclopramide were reported. Metoclopramide was found to be safe and effective for the treatment of HAC. PMID:27028980

  8. Efficacy of Bosentan in patients after Fontan procedures: a double-blind, randomized controlled trial.

    PubMed

    Shang, Xiao-Ke; Lu, Rong; Zhang, Xi; Zhang, Chang-Dong; Xiao, Shu-Na; Liu, Mei; Wang, Bin; Dong, Nian-Guo

    2016-08-01

    Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments. PMID:27465329

  9. Recruitment and retention of urban schoolchildren into a randomized double-blind vitamin D supplementation trial

    PubMed Central

    Sacheck, Jennifer M.; Van Rompay, Maria I.; Olson, Elizabeth M.; Chomitz, Virginia R.; Goodman, Elizabeth; Gordon, Catherine M.; Eliasziw, Misha; Holick, Michael F.; Economos, Christina D.

    2014-01-01

    Background While rarely used for supplementation trials in the U.S., schools present a practical alternative to a clinical setting. Purpose We describe the successful recruitment and retention of urban schoolchildren into a 6-month randomized, double-blind vitamin D3 supplementation trial. Methods Boston-area urban schoolchildren, aged 8-15 years, were recruited in 2011-2012 through classroom and auditorium presentations. Informed consent forms in five languages were sent home to parents. Retention methods included regular telephone calls and gift cards for completed study visits. Results In total, 691 schoolchildren enrolled. Their mean (SD) age was 11.7 (1.4) years; 59% were from racial/ethnic minorities and 68% qualified for free or reduced-price school meals. Multi-level, culturally-sensitive, creative approaches contributed to success in recruitment and retention. Of 691 participants, 81% completed the 6-month intervention period. Reasons for attrition included missed appointments and fear of a blood draw. More children from households with higher incomes were retained than those from households with lower incomes (85% vs. 79%, respectively, P=0.04). Limitations The need for three fasting blood draws over the 6-month supplementation period was a limiting factor in the recruitment and retention of children in this study. Conclusions Recruitment of urban children into a school-based randomized controlled trial represents a feasible approach for a supplementation study. Particular attention to children of lower socioeconomic status may enhance participation and retention when conducting intervention studies among diverse populations. PMID:25349179

  10. Double-blind, randomized, controlled, crossover trial of pregabalin for neurogenic claudication

    PubMed Central

    Frazer, Maria E.; Rast, Shirley A.; McDermott, Michael P.; Gewandter, Jennifer S.; Chowdhry, Amit K.; Czerniecka, Kate; Pilcher, Webster H.; Simon, Lee S.; Dworkin, Robert H.

    2015-01-01

    Objectives: To test the effects of pregabalin on the induction of neurogenic claudication. Methods: This study was a randomized, double-blind, active placebo-controlled, 2-period, crossover trial. Twenty-nine subjects were randomized to receive pregabalin followed by active placebo (i.e., diphenhydramine) or active placebo followed by pregabalin. Each treatment period lasted 10 days, including a 2-step titration. Periods were separated by a 10-day washout period, including a 3-day taper phase after the first period. The primary outcome variable was the time to first moderate pain symptom (Numeric Rating Scale score ≥4) during a 15-minute treadmill test (Tfirst). Secondary outcome measures included pain intensity at rest, pain intensity at the end of the treadmill test, distance walked, and validated self-report measures of pain and functional limitation including the Roland-Morris Disability Questionnaire, modified Brief Pain Inventory–Short Form, Oswestry Disability Index, and Swiss Spinal Stenosis Questionnaire. Results: No significant difference was found between pregabalin and active placebo for the time to first moderate pain symptom (difference in median Tfirst = −1.08 [95% confidence interval −2.25 to 0.08], p = 0.61). In addition, none of the secondary outcome measures of pain or functional limitation were significantly improved by pregabalin compared with active placebo. Conclusions: Pregabalin was not more effective than active placebo in reducing painful symptoms or functional limitations in patients with neurogenic claudication associated with lumbar spinal stenosis. Classification of evidence: This study provides Class I evidence that for patients with neurogenic claudication, compared with diphenhydramine, pregabalin does not increase the time to moderate pain during a treadmill test. PMID:25503625

  11. Bifidobacterium lactis in Treatment of Children with Acute Diarrhea. A Randomized Double Blind Controlled Trial

    PubMed Central

    El-Soud, Neveen Helmy Abou; Said, Reem Nabil; Mosallam, Dalia Sayed; Barakat, Nahla Abdel Moniem; Sabry, Mohamed Ahmed

    2015-01-01

    BACKGROUND: Probiotics are becoming increasingly popular treatment for children diarrhea. Although there are several probiotic strains potentially useful, researches were often limited to certain strains. AIM: To test Bifidobacterium lactis on morbidity of acute diarrhea in children less than 2 years. SUBJECTS AND METHODS: A randomized double-blind controlled clinical trial was conducted in 50 children (1 - 23 months) admitted with acute diarrhea to the Pediatric Hospital, Cairo University and were randomly assigned to receive in addition to usual treatment of diarrhea according to WHO guidelines; one of two treatments either milk formula non-supplemented (n = 25) or supplemented (n = 25) with Bifidobacterium lactis 14.5 × 106 CFU/100 ml daily for one week. Primary outcomes were frequency and duration of diarrhea and hospital stay. Secondary outcomes were duration of fever and vomiting episodes. Safety and tolerance were also recorded. RESULTS: On admission, patients’ characteristics of both groups (50 cases) were similar. For children who received the probiotics for one week; mean duration of diarrhoea was shorter than in controls (3.12 ± 0.92 vs. 4.10 ± 0.94 days) (P = 0.02), number of motions per day was less than in controls (3.96 ± 0.62 vs. 4.46 ± 0.85) (P = 0.04) and discharge from hospital <2 days was more frequent than in controls (72% vs. 44%) (P = 0.048). There was no effect on fever (P = 0.63) or vomiting (P = 0.54). CONCLUSION: Bifidobacterium lactis probiotics in supplemented milk formula decreased significantly frequency, duration of diarrhea, and hospital stay than usual treatment alone in children with acute diarrhea. Additional researches on other uncommon local probiotic species should be encouraged. PMID:27275258

  12. 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

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

    PubMed

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

    2014-11-01

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

  14. Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

    PubMed Central

    2011-01-01

    Background Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. Methods A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). Results There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. Conclusions Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means. PMID:21299861

  15. Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial

    PubMed Central

    van Samkar, Ganapathy; Eshuis, Wietse J.; Bennink, Roelof J.; van Gulik, Thomas M.; Dijkgraaf, Marcel G. W.; Preckel, Benedikt; de Hert, Stefan; Gouma, Dirk J.; Hollmann, Markus W.; Busch, Olivier R. C.

    2015-01-01

    Background Perioperative fluid restriction in a variety of operations has shown improvement of: complications, recovery of gastrointestinal function and length of stay (LOS). We investigated effects of crystalloid fluid restriction in pancreatic surgery. Our hypothesis: enhanced recovery of gastrointestinal function. Methods In this double-blinded randomized trial, patients scheduled to undergo pancreatoduodenectomy (PD) were randomized: standard (S:10ml/kg/hr) or restricted (R:5ml/kg/hr) fluid protocols. Primary endpoint: gastric emptying scintigraphically assessed on postoperative day 7. Results In 66 randomized patients, complications and 6-year survival were analyzed. 54 patients were analyzed in intention to treat: 24 S-group and 30 R-group. 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis. The median gastric emptying time (T½) was 104 minutes (S-group, 95% confidence interval: 74–369) versus 159 minutes (R-group, 95% confidence interval: 61–204) (P = 0.893, NS). Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group (45% and 50%, P = 0.779, NS). The primary outcome parameter, gastric emptying time, did not show a statistically significant difference between groups. Conclusion A fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying. A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery. Trial registration ISRCTN62621488 PMID:26465290

  16. 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

  17. Pimpinella anisum in the treatment of functional dyspepsia: A double-blind, randomized clinical trial

    PubMed Central

    Ghoshegir, S. Ashraffodin; Mazaheri, Mohammad; Ghannadi, Alireza; Feizi, Awat; Babaeian, Mahmoud; Tanhaee, Maryam; Karimi, Mehrdad; Adibi, Peyman

    2015-01-01

    Background: We aimed to evaluate the effects of Pimpinella anisum (anise) from Apiaceae family on relieving the symptoms of postprandial distress syndrome (PDS) in this double-blind randomized clinical trial. Materials and Methods: Totally, 107 patients attending the gastroenterology clinic, aged 18-65 years, diagnosed with PDS according to ROME III criteria and signed a written consent form were enrolled. They were randomized to receive either anise or placebo, blindly, for 4 weeks. Anise group included 47 patients and received anise powders, 3 g after each meal (3 times/day). Control group involved 60 patients and received placebo powders (corn starch), 3 gafter each meal (3 times/day). The severity of Functional dyspepsia (FD) symptoms was assessed by FD severity scale. Assessments were done at baseline and by the end of weeks 2, 4 and 12. Mean scores of severity of FD symptoms and the frequency distribution of patients across the study period were compared. Results: The age, sex, body mass index, smoking history, and coffee drinking pattern of the intervention and control groups were not significantly different. Mean (standard deviation) total scores of FD severity scale before intervention in the anise and control groups were 10.6 (4.1) and 10.96 (4.1), respectively (P = 0.6). They were 7.04 (4.1) and 12.30 (4.3) by week 2, respectively (P = 0.0001), 2.44 (4.2) and 13.05 (5.2) by week 4, respectively (P = 0.0001), and 1.08 (3.8) and 13.30 (6.2) by week 12, respectively (P = 0.0001). Conclusion: This study showed the effectiveness of anise in relieving the symptoms of postpartum depression. The findings were consistent across the study period at weeks 2, 4 and 12. PMID:25767516

  18. [Double-blind study of mianserin and fluoxetine in ambulatory therapy of depressed patients].

    PubMed

    Besançon, G; Cousin, R; Guitton, B; Lavergne, F

    1993-01-01

    A double blind controlled trial was carried out in 65 depressed out-patients to compare the efficacy and tolerance of mianserin with fluoxetine. The two compounds present very different pharmacological activities. Mianserin is an antagonist of the alpha 2-adrenergic receptors, while fluoxetine is an inhibitor of recapture specific to serotonin. Requirements for inclusion were: depressive episode of less than 2 months duration, meeting the criteria for one of the sub-types of depression described in DSM III, with a minimum score of 25 on the Montgomery Asberg Depressive Rating Scale (MADRS). The patient's ages ranged from 18 to 65. The only psychotropic medication allowed in association to the treatment was prazepam (up to 40 mg/day). Patients gave their written consent to the study. Assessment, using the Montgomery Asberg Depression Rating Scale (MADRS), the HARD diagram, the check list for somatic symptoms and side-effects was carried out before treatment and at the end of weeks 2, 4, 8. Assessment of anxiety using the Hamilton Anxiety Rating Scale (HARS) and of sleep disturbances using a sleep questionnaire was carried out before treatment and at week 4. The 8 items of the sleep questionnaire covers the complaints listed in criteria for insomnia disorders (307.42 DSM III-R). Clinical Global Impression (CGI), Therapeutic Index (TI), Tolerance Global Impression were assessed at end-point. The 2 groups were strictly comparable in respect to the clinical status at base line (diagnosis, history and duration of the depressive illness, MADRS and HARD diagram scores).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8275922

  19. Generic inhaled salbutamol versus branded salbutamol. A randomised double-blind study.

    PubMed

    Williamson, I J; Reid, A; Monie, R D; Fennerty, A G; Rimmer, E M

    1997-03-01

    Generic substitution of salbutamol lags behind that of other drugs in Scotland and a negative perception by both patients and doctors may explain this. The aim of this study was to assess whether, in clinical practice, there was any difference in efficacy between branded salbutamol (Ventolin) and a generic preparation. Asthmatic patients using a Ventolin metered-dose inhaler at least twice a day for symptom relief were entered into a double-blind cross-over study, comparing Ventolin, blinded Ventolin and a generic salbutamol in random order for two weeks each. Daily peak flows, inhaler use and bronchodilator response were recorded. At the end of each treatment period patients rated their inhaler against their usual Ventolin on a 5-point scale. Forty patients were entered into the study; 90% received 1000 micrograms or more of inhaled steroids per day. Eleven patients dropped out during the run-in phase. In the remaining 29 patients, no significant difference between treatments could be found in any of the objective parameters measured. Fifty-five per cent of patients said they could detect a difference between the inhalers, and 45% noted a difference between their usual Ventolin and the open or blinded Ventolin. This study showed clinical equivalence between a generic and branded salbutamol. Patients' own assessment of their relief inhaler seems to be influenced by factors other than efficacy. The study highlights that careful encouragement is required when changing to a generic product and has particular implications for the forthcoming conversion to CFC-free products. PMID:9135831

  20. Generic inhaled salbutamol versus branded salbutamol. A randomised double-blind study.

    PubMed Central

    Williamson, I. J.; Reid, A.; Monie, R. D.; Fennerty, A. G.; Rimmer, E. M.

    1997-01-01

    Generic substitution of salbutamol lags behind that of other drugs in Scotland and a negative perception by both patients and doctors may explain this. The aim of this study was to assess whether, in clinical practice, there was any difference in efficacy between branded salbutamol (Ventolin) and a generic preparation. Asthmatic patients using a Ventolin metered-dose inhaler at least twice a day for symptom relief were entered into a double-blind cross-over study, comparing Ventolin, blinded Ventolin and a generic salbutamol in random order for two weeks each. Daily peak flows, inhaler use and bronchodilator response were recorded. At the end of each treatment period patients rated their inhaler against their usual Ventolin on a 5-point scale. Forty patients were entered into the study; 90% received 1000 micrograms or more of inhaled steroids per day. Eleven patients dropped out during the run-in phase. In the remaining 29 patients, no significant difference between treatments could be found in any of the objective parameters measured. Fifty-five per cent of patients said they could detect a difference between the inhalers, and 45% noted a difference between their usual Ventolin and the open or blinded Ventolin. This study showed clinical equivalence between a generic and branded salbutamol. Patients' own assessment of their relief inhaler seems to be influenced by factors other than efficacy. The study highlights that careful encouragement is required when changing to a generic product and has particular implications for the forthcoming conversion to CFC-free products. PMID:9135831

  1. Evaluation of Oral Ginger Efficacy against Postoperative Nausea and Vomiting: A Randomized, Double - Blinded Clinical Trial

    PubMed Central

    Montazeri, Akram Sadat; Hamidzadeh, Azam; Raei, Mehdi; Mohammadiun, Malihe; Montazeri, Azam Sadat; Mirshahi, Reza; Rohani, Hosein

    2013-01-01

    Background: Postoperative nausea and vomiting is one of the most common side effects associated with surgical procedures. Objectives: The aim of this study was to determine the effect of ginger on intensity of nausea and vomiting after surgical procedures. Patients and Methods: This study was a randomized, double blinded, clinical trial. 160 eligible patients were randomly assigned into experimental or placebo groups. The experimental group received 4 capsules containing 250 mg ginger and placebo group received 4 placebo capsules 1 hour before surgery. The severity of nausea and vomiting was measured at 2, 4, 6 hours post operation using visual analogue scale and a structured questionnaire. The data were analyzed by independent t - test, Mann-Whitney U test, chi –square and GEE using SPSS 16 and STATA version 11. Results: Mean nausea score at 2 hours post operation was significantly lower in the experimental group (P= 0.04). Mean nausea score at 4 and 6 hours post operation was lower in the experimental group; however, there was no significant difference between the groups at any time post operation. The frequencies of nausea in the experimental group at 2 and 6 hours post operation were lower than that in the placebo group, however, at 2 hours post operation, it was borderline significant (P = 0.05) There was no significant differences between two group in the intensity of vomiting at any time. Conclusions: Use of ginger was effective at decreasing postoperative nausea. Ginger could be used as a safe antiemetic drug at post operation. PMID:24693389

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

    PubMed

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

    2007-12-01

    In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration. PMID:17998023

  3. Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial.

    PubMed

    Buigues, Cristina; Fernández-Garrido, Julio; Pruimboom, Leo; Hoogland, Aldert J; Navarro-Martínez, Rut; Martínez-Martínez, Mary; Verdejo, Yolanda; Mascarós, Mari Carmen; Peris, Carlos; Cauli, Omar

    2016-01-01

    Aging can result in major changes in the composition and metabolic activities of bacterial populations in the gastrointestinal system and result in impaired function of the immune system. We assessed the efficacy of prebiotic Darmocare Pre(®) (Bonusan Besloten Vennootschap (BV), Numansdorp, The Netherlands) to evaluate whether the regular intake of this product can improve frailty criteria, functional status and response of the immune system in elderly people affected by the frailty syndrome. The study was a placebo-controlled, randomized, double blind design in sixty older participants aged 65 and over. The prebiotic product was composed of a mixture of inulin plus fructooligosaccharides and was compared with placebo (maltodextrin). Participants were randomized to a parallel group intervention of 13 weeks' duration with a daily intake of Darmocare Pre(®) or placebo. Either prebiotic or placebo were administered after breakfast (between 9-10 a.m.) dissolved in a glass of water carefully stirred just before drinking. The primary outcome was to study the effect on frailty syndrome. The secondary outcomes were effect on functional and cognitive behavior and sleep quality. Moreover, we evaluated whether prebiotic administration alters blood parameters (haemogram and biochemical analysis). The overall rate of frailty was not significantly modified by Darmocare Pre(®) administration. Nevertheless, prebiotic administration compared with placebo significantly improved two frailty criteria, e.g., exhaustion and handgrip strength (p < 0.01 and p < 0.05, respectively). No significant effects were observed in functional and cognitive behavior or sleep quality. The use of novel therapeutic approaches influencing the gut microbiota-muscle-brain axis could be considered for treatment of the frailty syndrome. PMID:27314331

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

    PubMed Central

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

    2014-01-01

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

  5. 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

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

    PubMed Central

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

    2016-01-01

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

  7. Randomised, double blind, placebo‐controlled trial of selenium supplementation in adult asthma

    PubMed Central

    Shaheen, Seif O; Newson, Roger B; Rayman, Margaret P; Wong, Angela P‐L; Tumilty, Michael K; Phillips, Joanna M; Potts, James F; Kelly, Frank J; White, Patrick T; Burney, Peter G J

    2007-01-01

    Background Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. Methods A randomised, double blind, placebo‐controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high‐selenium yeast preparation (100 µg daily, n = 99) or placebo (yeast only, n = 98) for 24 weeks. The primary outcome was asthma‐related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by “intention to treat”. Results There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (−0.05 (95% CI −0.19 to 0.09); p = 0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. Conclusions Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids. PMID:17234657

  8. Double-Blind Placebo Controlled Trial of Dapsone in Antihistamine Refractory Chronic Idiopathic Urticaria

    PubMed Central

    Morgan, Matt; Cooke, Andrew; Rogers, Laura; Adams-Huet, Beverley; Khan, David A.

    2014-01-01

    Background Management of antihistamine refractory CIU has poorly defined therapeutic options. Objective To evaluate the efficacy of dapsone in antihistamine refractory CIU compared to placebo. Methods Twenty-two patients with antihistamine refractory CIU were randomly assigned to 100 mg of dapsone daily or placebo for 6 weeks in a 14 week double-blind, placebo-controlled crossover trial. Endpoints were measured from a daily diary reflecting weekly hive score (WHS) and weekly itch score (WIS) and a visual analog score. Secondary to a carryover effect, the first period results were analyzed as a parallel design comparing placebo to dapsone directly using repeated measures analysis. Results After 6 weeks patients in the dapsone arm showed mean improvement over baseline in VAS (+2.3 [0.6,4.1], p=0.01), urticaria score (-3.5 [-6.2, -0.9], p=0.01), and itch score (-4.8 [-7.6, -2.1], p=0.001), whereas the placebo arm showed no improvement over baseline for VAS, urticaria or itch scores. Dapsone showed greater improvement compared to placebo for itch (p=0.047) and VAS (p=0.04). Of the 22 patients, 3 showed complete resolution of hives and itch with dapsone, while 31% and 41% had ≥ 50% resolution of hives and itch respectively. No serious adverse effects were observed from dapsone. Conclusion To our knowledge, this is the first DBPC study of dapsone in CIU and suggests dapsone has efficacy in antihistamine refractory CIU patients. PMID:25213055

  9. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema.

    PubMed

    Henz, B M; Jablonska, S; van de Kerkhof, P C; Stingl, G; Blaszczyk, M; Vandervalk, P G; Veenhuizen, R; Muggli, R; Raederstorff, D

    1999-04-01

    Although gamma-linolenic acid (GLA) has been shown to correct deficiencies in skin lipids associated with reduced delta-6-desaturase activity which should result in improvement of dysregulation of inflammation and immunity in atopic eczema, clinical studies with evening primrose oil containing 10% GLA have yielded contradictory results. We have therefore examined the effect of a higher percentage (at least 23%) GLA-containing borage oil in adults with stable atopic eczema of moderate severity in a double-blind, multicentre study. One hundred and sixty patients were randomized to take daily either 500 mg of borage oil-containing capsules or the bland lipid miglyol as a placebo over a 24-week period. Use of topical diflucortolone-21-valerate cream was allowed as rescue medication, with the amount used until response being defined as primary, and clinical improvement as secondary efficacy criteria. Although several clinical symptoms improved compared with placebo, the overall response to borage oil did not reach statistical significance. Significant differences in favour of borage oil were, however, observed in a subgroup excluding patients who failed to show increased erythrocyte dihomo-gamma-linolenic acid levels and in whom adherence to inclusion criteria and the study protocol were questionable. GLA metabolites increased in borage oil-treated patients only, and serum IgE showed a trend to decrease on overall and subgroup analysis. No substance-related adverse effects were observed. This study shows no overall efficacy of GLA-containing borage oil in atopic eczema, with steroid use being the primary response parameter, although it suggests that a subgroup of patients may benefit from this well-tolerated treatment. PMID:10233322

  10. 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

  11. Oral clonidine and gabapentin suppress pressor response: A prospective, randomized, double blind study

    PubMed Central

    Kapse, Upendra Kumar S.; Bhalerao, Pradnya Milind

    2016-01-01

    Background: Pressor response is a part of stress response caused by reflex sympathetic discharge due to direct laryngoscopy and tracheal intubation resulting in tachycardia, hypertension and arrhythmias. Both clonidine, and gabapentin administered orally can effectively blunt this detrimental hemodynamic response. Aim: To study the effect of oral clonidine to blunt the pressor response to direct laryngoscopy and to compare it with oral gabapentin. To observe for postoperative sedation and side effects if any. Settings and Design: Sixty patients of American Society of Anaesthesiologist Grade I and II scheduled for surgery under general anesthesia were considered in this prospective randomized double-blind study. They were randomly allocated into two groups of 30 each using computerized randomization. Materials and Methods: Group A was given oral clonidine 5 μg/kg and Group B was given oral gabapentin 800 mg. Both the drugs were given 90 min prior to surgery. Heart rate (HR) and blood pressure were monitored at baseline, 0, 1, 3, 5, 10, 15, and 30th min of laryngoscopy. Sedation was monitored by Ramsay Sedation Scale score and side effects were noted. Results: HR decreased in both groups at 0 and 1 min, increased at 3rd min and gradually decreased by 30th min. Statistically, significant difference was found between two groups at 1, 3, 5, 10, and 15th min (P < 0.05). Though there was no significant difference in systolic blood pressure, diastolic blood pressure and mean arterial pressure between the two groups, there was no rise in these parameters. Gabapentin produced more sedation than clonidine postoperatively, and few side effects were noted. Conclusion: Both oral clonidine and gabapentin are effective in obtunding pressor response to direct laryngoscopy, clonidine being better in terms of controlling HR. Gabapentin produces more postoperative sedation than clonidine. PMID:26957684

  12. Double blind randomised controlled trial of two different breathing techniques in the management of asthma

    PubMed Central

    Slader, C A; Reddel, H K; Spencer, L M; Belousova, E G; Armour, C L; Bosnic‐Anticevich, S Z; Thien, F C K; Jenkins, C R

    2006-01-01

    Background Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non‐specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. Methods After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. Results Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. Conclusion Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non‐specific upper body exercises. PMID:16517572

  13. Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children

    PubMed Central

    Ochoa, Theresa J.; Chea-Woo, Elsa; Baiocchi, Nelly; Pecho, Iris; Campos, Miguel; Prada, Ana; Valdiviezo, Gladys; Lluque, Angela; Lai, Dejian; Cleary, Thomas G.

    2012-01-01

    Objective To determine the effect of bovine lactoferrin on prevention of diarrhea in children. Study design We conducted a community-based randomized double-blind placebo controlled trial comparing supplementation with bovine lactoferrin versus placebo. Previously weaned children were enrolled at 12–18 months and followed for 6 months with daily home visits for data collection and supplement administration. Anthropometric measures were done monthly. Results 555 children were randomized: 277 to lactoferrin and 278 to placebo; 65 dropped out; 147,894 doses were administered (92% compliance). Overall there were 91,446 child-days of observation and 1,235 diarrhea episodes lasting 6,219 days. The main pathogens isolated during diarrheal episodes were norovirus (35.0%), enteropathogenic E. coli (11.4%), Campylobacter (10.6%), enteroaggregative E. coli (8.4%), enterotoxigenic E. coli (6.9%) and Shigella (6.6%). The diarrhea incidence was not different between groups: 5.4 vs. 5.2 episodes/child/year for lactoferrin and placebo, respectively (p=0.375). However, the diarrhea longitudinal prevalence was lower in the lactoferrin group (6.6% vs. 7.0%, p=0.017) as well as the median duration of episodes (4.8 vs. 5.3 days, p=0.046), proportion of episodes with moderate or severe dehydration (1.0% vs. 2.6%, p=0.045) and liquid stools load (95.0 vs. 98.6) liquid stools/child/year, p<0.001). There were no adverse events related to the intervention. Conclusions Although there was no decrease in diarrhea incidence, longitudinal prevalence and severity were decreased with lactoferrin. PMID:22939927

  14. Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis

    PubMed Central

    Balaskas, Elias; Szepietowski, Jacek C.; Bessis, Didier; Ioannides, Dimitrios; Ponticelli, Claudio; Ghienne, Corinne; Taberly, Alain

    2011-01-01

    Summary Background and objectives Uremic xerosis is a bothersome condition that is poorly responsive to moisturizing and emollient therapy. Design, setting, participants, & measurements A randomized, double-blind, intraindividual (left versus right comparison), multicentric clinical study was performed on 100 patients with moderate to severe uremic xerosis for 7 days, during which the patients applied twice daily an emulsion combining glycerol and paraffin (test product) on one allocated lower leg, and the emulsion alone (comparator) on the other lower leg. This was followed by an open-labeled use of the test product on all of the xerotic areas for 49 days. The main efficacy parameter was treatment response on each lower leg, as defined by a reduction from baseline of at least two grades in a five-point clinical score on day 7. Results Among the 99 patients analyzed, the test product was highly effective with a treatment response in 72 patients (73%), whereas 44 patients (44%) responded to the comparator (P < 0.0001, intergroup analysis). This was associated with an objective reduction in the density and thickness of the scales on day 7 (P < 0.0001 compared with the comparator) and a substantial improvement of the uremic pruritus (75%) and quality of life of the patients at study end (P < 0.001, intragroup analysis). The test product was very well tolerated, with product-related local intolerance (exacerbated pruritus, local burning, or erythema) occurring in only five patients (5%). Conclusions Uremic xerosis can be managed successfully when an appropriate emollient therapy is used. PMID:21258039

  15. A Double Blind, within Subject Comparison of Spontaneous Opioid Withdrawal from Buprenorphine versus Morphine

    PubMed Central

    Smith, Michael T.; Mintzer, Miriam Z.; Campbell, Claudia M.; Strain, Eric C.

    2014-01-01

    Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0–100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID:24227768

  16. The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study

    PubMed Central

    Moon, Jee Youn; Lee, Shin Young; Lee, Mi Kyung; Kim, Jung Eun; Lee, Ji Eun; Lee, So Hyun

    2016-01-01

    Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). Methods Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl 1,000 µg; Group B, fentanyl 500 µg + nefopam 200 mg; and Group C, fentanyl 500 µg + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. Results Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. Conclusions The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects. PMID:27103966

  17. Double-blind parallel comparison of ketoprofen (Orudis), acetaminophen plus codeine, and placebo in postoperative pain.

    PubMed

    Turek, M D; Baird, W M

    1988-12-01

    One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind, randomized, parallel study designed to compare the efficacy and safety of single oral doses of ketoprofen (50 and 150 mg), an acetaminophen (650 mg) plus codeine (60 mg) combination, and placebo. From 1 through 4 hours after administration of the study drugs, the mean summed pain intensity difference (SPID) and time-weighted total pain relief (TOPAR) scores for the three active treatments generally were significantly (P less than 0.05) higher than those for placebo but not significantly different from each other. At the 6-hour evaluation, the ketoprofen groups, but not the acetaminophen-codeine group, had higher (P less than 0.05) mean SPID and TOPAR scores than the placebo group, as a result of a shorter duration of pain relief in the acetaminophen-codeine group. The 6-hour TOPAR scores were significantly (P less than 0.05) higher for both ketoprofen groups than for the acetaminophen-codeine group; the ketoprofen 150 mg group also had significantly (P less than 0.05) higher mean 6-hour SPID and global subjective assessment scores. As a result of a higher frequency of somnolence, there was a significantly (P less than 0.05) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen. These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer. PMID:3072354

  18. Effect of xylitol on cariogenic and beneficial oral streptococci: a randomized, double-blind crossover trial

    PubMed Central

    Bahador, A; Lesan, S; Kashi, N

    2012-01-01

    Background/purpose Although habitual consumption of xylitol reduces cariogenic streptococci levels, its effect on beneficial oral streptococci is less clear. The main aim of the study is to investigate the effect of short-term xylitol consumption on the oral beneficial streptococci level of saliva, Streptococcus sanguinis and S. mitis. Material and Methods Twenty four volunteers with a median age of 23.7 years (range: 20-28) harboring Streptococcus mutans, S. sobrinus, S. sanguinis and S. mitis participated in the randomized, double-blind, cross-over study. The experimental chewing gum (1.5 g/pellet) contained 70% xylitol w/w while the control gum contained 63% sorbitol w/w. Saliva samples were collected before and after two three-week test periods with a four-week washout interval. Colony-forming units (CFU)/ml were enumerated for the estimation of S. mutans levels on Mitis Salivarius-Mutans valinomycin (MS-MUTV), S. sobrinus on Mitis Salivarius-Sobrinus (MS-SOB), S. sanguinis on Modified Medium 10-Sucrose (MM10-S) and S. mitis on Mitis Salivarius Agar with Tellurite (MSAT) media. Results The S. mutans and S. sobrinus counts of the saliva samples decreased significantly (p = 0.01 and p = 0.011, respectively) in the xylitol gum group but not in the sorbitol gum group. The salivary S. sanguinis and S. mitis counts did not decrease in both xylitol and sorbitol gum groups. Conclusions Based on the findings of this study, xylitol consumption reduced S. mutans and S. sobrinus counts in saliva but appeared not to effect numbers of S. sanguinis and S. mitis in saliva. So, habitual consumption of xylitol reduces cariogenic streptococci levels without any effect on beneficial sterptococci for the oral cavity. PMID:22973473

  19. Use of probiotics in HIV-infected children: a randomized double-blind controlled study.

    PubMed

    Trois, Lívia; Cardoso, Edmundo Machado; Miura, Ernani

    2008-02-01

    HIV/AIDS is an infection characterized by immune cell dysfunction and subsequent immunodeficiency, as well as intestinal disorder. Probiotics are live microbial feed supplements that beneficially affect the host animal by improving intestinal microbial balance and promoting health benefits. The goals of this study were to determine whether the use of probiotics could improve the immune response determined by CD4 cells mm(-3) counts and reduce liquid stool episodes. A randomized double-blind controlled trial with 77 HIV-infected children (2-12 years), divided into two groups: one receiving probiotics (formula containing Bifidobacterium bifidum with Streptococcus thermophilus -2.5 x 10(10) colony forming units) and the other, a standard formula (control group), for 2 months. The CD4 counts (cells mm(-3)) were collected at the beginning and end of the study. The quality and number of stools were assessed by a questionnaire (watery to normal stool consistency). There was an increase in the mean CD4 count in the probiotics group (791 cells mm(-3)) and a small decrease in the control group (538 cells mm(-3)). The change from baseline in mean CD4 cell count was +118 cells mm(-3) vs. -42 cells mm(-3) for children receiving the probiotic formula and control formula, respectively (p = 0.049). A similar reduction in liquid stool consistency in both the groups (p < 0.06), with a slight enhancement in the probiotics group, was observed, but without significant difference (p < 0.522). The incidence of loose-soft stools showed a small decrease in both groups (p < 0.955) and there was an increase in the incidence of normal stool consistency in both the groups (p < 0.01). Our study showed that probiotics have immunostimulatory properties and might be helpful in the treatment of HIV-infected children. PMID:17878180

  20. Perioperative synbiotics decrease postoperative complications in periampullary neoplasms: a randomized, double-blind clinical trial.

    PubMed

    Sommacal, Heloisa Martins; Bersch, Vivian Pierri; Vitola, Santo Pascoal; Osvaldt, Alessandro Bersch

    2015-01-01

    Periampullary neoplasms are rapidly progressive tumors with a poor prognosis and high morbidity and mortality rates, which have a negative influence on patient outcomes. Some probiotics and prebiotics have the ability to protect the intestinal barrier and prevent bacterial translocation, infection, and postoperative complications. We evaluated the use of synbiotics in a prospective, double-blind study of patients undergoing surgery for periampullary neoplasms (PNs) and assessed the effect of these agents on nutritional status, postoperative complications, antibiotic use, length of hospital stay, and mortality. Patients were randomized to receive probiotics and prebiotics-synbiotics--group S [Lactobacillus acidophilus 10, 1 × 10(9)CFU, Lactobacillus rhamnosus HS 111, 1 × 10(9) CFU, Lactobacillus casei 10, 1 × 10(9) CFU, Bifidobacterium bifidum, 1 × 10(9)CFU, and fructooligosaccharides (FOS) 100 mg]--or placebo-controls--group C, twice daily, for a total of 14 days. Risk, clinical status, and postoperative complication rates were assessed. Twenty-three patients were allocated to each group. The incidence of postoperative infection was significantly lower in group S (6 of 23 patients, 26.1%) than in group C (16 of 23 patients, 69.6%) (P = 0.00). Duration of antibiotic therapy was also shorter in group S (mean = 9 days vs. 15 days in group C; P = 0.01). Noninfectious complications were less common in group S (6 of 23 vs. 14 of 23 patients in group C; P = 0.03). Mean length of hospital stay was 12 ± 5 days in group S vs. 23 ± 14 days in group C (P = 0.00). No deaths occurred in group S, whereas 6 deaths occurred in group C (P = 0.02). Perioperative administration of synbiotics reduces postoperative mortality and complication rates in patients undergoing surgery for PNs. PMID:25803626

  1. Lysine clonixinate in minor dental surgery: double-blind randomized parallel study versus paracetamol.

    PubMed

    Martí, M L; De los Santos, A R; Di Girolamo, G; Gil, M; Manero, E O; Fraga, C

    1993-01-01

    Lysine clonixinate (LC), an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase, was assessed with a double-blind randomized dummy design versus paracetamol (P) on 200 patients suffering from pain after minor dental surgery. Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief. Both groups, each composed of 100 patients, were comparable in terms of demographic conditions (t test), initial symptoms (chi-square test), characteristics of the extracted dental pieces, surgical complications and wound treatment (chi-square test). Pain intensity scores and daily average intake of tablets (3.4/day) documented in the patients' diary revealed no statistically significant differences between the two treatments (chi-square test). It was found that spontaneous pain measured using a visual analogue scale (VAS) decreased significantly in both treatment groups at the 24-h control examination. The following values were observed in the LC group: baseline 4.38 +/- 1.7; 24-h * 1.20 +/- 1.4; 48-h * 0.36 +/- 1.2. In the P group the values were: baseline 4.28 +/- 1.6; 24-h * 1.11 +/- 1.4; 48-h * 0.30 +/- 0.7 (*p < 0.05). Other variables like facial swelling and night pain, evaluated on a score from 0 to 4 and symptom presence or absence respectively, showed a similar response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8077090

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

    PubMed

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

    2001-01-01

    We studied 125 patients with primary dysmenorrhea in a prospective randomized double-blind crossover study. After an admission pretreatment period without medication, the patients completed three consecutive randomized treatment phases with lysine clonixinate 125 mg plus propinox 10 mg or paracetamol 500 mg plus hyoscine N-butylbromide 10 mg or placebo, according to a fixed-dose schedule of 1 tablet every 6 h, 3 days before onset of menses and for 5 days thereafter. Changes in menstrual pain intensity and duration, amount of bleeding measured according to the number of daily pads used and concomitant symptoms were assessed on the fifth day of each cycle. Every night, the patients recorded the average intensity of menstrual pain during the first 4 days of menstruation in a diary The follow-up visit carried out at day 5 showed significant reduction in pain intensity with both active treatments vs. the other two phases: baseline: 2.72 +/- 0.61; placebo: 1.85 +/- 0.87; lysine clonixinate plus propinox 1.36 +/- 0.81, and paracetamol plus hyosine N-butylbromide: 1.45 +/- 0.87. The patients' diaries showed increasingly lower pain intensities starting from day 1 with the three treatments. Active treatments revealed significantly higher analgesic efficacy from the outset compared with baseline and placebo; however, only the lysine clonixinate plus propinox combination reached a statistically significant difference by days 3 and 4. No changes in duration or intensity of menstrual bleeding or in the incidence of adverse effects were observed during the four study periods. PMID:11708572

  3. A Double-Blind Placebo-Controlled Trial of Ruxolitinib for 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; Koumenis, Iphigenia L.; Sun, William; Sandor, Victor; Kantarjian, Hagop M.

    2016-01-01

    BACKGROUND Ruxolitinib, a selective JAK1 and JAK2 inhibitor, has clinically significant activity in myelofibrosis. METHODS In a double-blind trial, patients with intermediate-2 or high-risk myelofibrosis were randomized to twice-daily oral ruxolitinib (n=155) or placebo (n=154). The primary endpoint was the proportion of patients with ≥35% spleen volume reduction at 24 weeks assessed by magnetic resonance imaging. Secondary endpoints included durability of response, changes in symptom burden (assessed by Total Symptom Score [TSS]), and overall survival. RESULTS In the ruxolitinib group, 41.9% achieved the primary endpoint versus 0.7% in the placebo group (P<0.001). Spleen response was maintained while taking ruxolitinib: 67% of responding patients maintained response for ≥48 weeks. A ≥50% improvement in TSS at 24 weeks was achieved by 45.9% of ruxolitinib-treated versus 5.3% of placebo-treated patients (P<0.001). Thirteen deaths occurred in the ruxolitinib and 24 in the placebo group (hazard ratio, 0.50; 95% CI, 0.25–0.98; P=0.04). Discontinuations for adverse events were similar between groups (11% each). Among ruxolitinib-treated patients, anemia and thrombocytopenia were the most common adverse events, but rarely led to discontinuation (1 patient for each event). Two patients underwent transformation to acute myeloid leukemia (AML), both in the ruxolitinib group. CONCLUSIONS Ruxolitinib provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, improving debilitating myelofibrosis-related symptoms, and improving overall survival. Improvement came at a cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. The imbalance in AML transformation requires attention in further studies. (Funded by Incyte Corporation; ClinicalTrials.gov, NCT00952289) PMID:22375971

  4. 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

  5. The effect of gabapentin on muscle cramps during hemodialysis: A double-blind clinical trial.

    PubMed

    Beladi Mousavi, Seyed Seifollah; Zeraati, Abbasali; Moradi, Sajad; Mousavi, Marzieh Beladi

    2015-11-01

    Hemodialysis-associated muscle cramps (HAMC) are a common complication during hemodialysis (HD) sessions. A number of pharmacologic agents have been evaluated to prevent and or diminish HAMC; however, none of them has an established role. To the best of our knowledge, this is the first study to evaluate the possible effect of gabapentin on HAMC. In a double-blinded clinical trial, we compared the possible effect of gabapentin with a placebo in prevention and or diminishing episodes of HAMC in HD patients who had experienced frequent intradialytic muscle cramps. At first, placebo was given before each dialysis session for four weeks and then, after a two-week washout period, 300 mg of gabapentin was given before each dialysis session for four weeks to verify the effect of gabapentin on HAMC. Overall, 15 patients (seven men and eight women; mean age, 52.02 years) with frequent intradialytic muscle cramps were enrolled in the study. The incidence of symptomatic muscle cramp decreased in the gabapentin group compared with the placebo group, with a significant difference between them (P = 0.001). The intensity of muscle cramps also decreased in the gabapentin group (P = 0.001). There was no significant association between HAMC in male and female patients (P = 0. 397), mean age of HD patients (P = 0.226) and cause of end-stage renal disease (P = 0.551). According to the results of our study, gabapentin prescription before each HD session significantly reduced the frequency and the intensity of muscle cramps during HD without any major side-effects. PMID:26586051

  6. Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus caffeine for acute migraine therapy.

    PubMed

    Láinez, M J A; Galván, J; Heras, J; Vila, C

    2007-03-01

    In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min (P < 0.05), phonophobia at 60, 90, and 120 min (P < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min (P < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine (P < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction. PMID:17355546

  7. 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

  8. Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.

    PubMed

    Meador, Kimford J; Loring, David W; Boyd, Alan; Echauz, Javier; LaRoche, Suzette; Velez-Ruiz, Naymee; Korb, Pearce; Byrnes, William; Dilley, Deanne; Borghs, Simon; De Backer, Marc; Story, Tyler; Dedeken, Peter; Webster, Elizabeth

    2016-09-01

    Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile. PMID:27517350

  9. Swahili 12 Weeks Course. Volume VI, Vocabulary List: Swahili-English, English-Swahili.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This Swahili-English/English-Swahili vocabulary list accompanies the Defense Language Institute's 12-weeks course in Swahili. For a description of the first five volumes (55 lesson units), see ED 026 651. (AMM)

  10. 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

  11. Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study

    PubMed Central

    Wade, C; Wang, L; Zhao, W J; Cardini, F; Kronenberg, F; Gui, S Q; Ying, Z; Zhao, N Q; Chao, M T; Yu, J

    2016-01-01

    Objective To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. Setting A Menstrual Disorder Centre at a public hospital in Shanghai, China. Participants Chinese women aged 14–25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. Interventions A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. Primary and secondary outcome measures The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. Results Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (−0.71, CI −1.37 to −0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. Conclusions Acupuncture point injection of

  12. Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in treatment of toenail onychomycosis

    PubMed Central

    Evans, E Glyn V; Sigurgeirsson, Bárdur

    1999-01-01

    Objective To compare the efficacy and safety of continuous terbinafine with intermittent itraconazole in the treatment of toenail onychomycosis. Design Prospective, randomised, double blind, double dummy, multicentre, parallel group study lasting 72 weeks. Setting 35 centres in six European countries. Subjects 496 patients aged 18 to 75 years with a clinical and mycological diagnosis of dermatophyte onychomycosis of the toenail. Interventions Study patients were randomly divided into four parallel groups to receive either terbinafine 250 mg a day for 12 or 16 weeks (groups T12 and T16) or itraconazole 400 mg a day for 1 week in every 4 weeks for 12 or 16 weeks (groups I3 and I4). Main outcome measures Assessment of primary efficacy at week 72 was mycological cure, defined as negative results on microscopy and culture of samples from the target toenail. Results At week 72 the mycological cure rates were 75.7% (81/107) in the T12 group and 80.8% (80/99) in the T16 group compared with 38.3% (41/107) in the I3 group and 49.1 % (53/108) in the I4 group. All comparisons (T12 v I3, T12 v I4, T16 v I3, T16 v I4) showed significantly higher cure rates in the terbinafine groups (all P<0.0001). Also, all secondary clinical outcome measures were significantly in favour of terbinafine at week 72. There were no differences in the number or type of adverse events recorded in the terbinafine or itraconazole groups. Conclusion Continuous terbinafine is significantly more effective than intermittent itraconazole in the treatment of patients with toenail onychomycosis. Key messagesGiven a correct diagnosis, fungal nail disease (onychomycosis) is curableTerbinafine is an allylamine antifungal with a primarily fungicidal mode of actionContinuous terbinafine treatment over 12 or 16 weeks achieves higher rates of clinical and mycological cure than intermittent itraconazole given over the same periodsTerbinafine is safe and well tolerated over 12 or 16 weeks of continuous treatment

  13. 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

  14. 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

  15. Amiloride Clinical Trial In Optic Neuritis (ACTION) protocol: a randomised, double blind, placebo controlled trial

    PubMed Central

    McKee, Justin B; Elston, John; Evangelou, Nikos; Gerry, Stephen; Fugger, Lars; Kennard, Christopher; Kong, Yazhuo; Palace, Jacqueline; Craner, Matthew

    2015-01-01

    Introduction Neurodegeneration is a widely accepted contributor to the development of long-term disability in multiple sclerosis (MS). While current therapies in MS predominantly target inflammation and reduce relapse rate they have been less effective at preventing long-term disability. The identification and evaluation of effective neuroprotective therapies within a trial paradigm are key unmet needs. Emerging evidence supports amiloride, a licenced diuretic, as a neuroprotective agent in MS through acid sensing ion channel blockade. Optic neuritis (ON) is a common manifestation of MS with correlates of inflammation and neurodegeneration measurable within the visual pathways. Amiloride Clinical Trial In Optic Neuritis (ACTION) will utilise a multimodal approach to assess the neuroprotective efficacy of amiloride in acute ON. Methods and analysis 46 patients will be recruited within 28 days from onset of ON visual symptoms and randomised on a 1:1 basis to placebo or amiloride 10 mg daily. Double-blinded treatment groups will be balanced for age, sex and visual loss severity by a random-deterministic minimisation algorithm. The primary objective is to demonstrate that amiloride is neuroprotective in ON as assessed by scanning laser polarimetry of the peripapillary retinal nerve fibre layer (RNFL) thickness at 6 months in the affected eye compared to the unaffected eye at baseline. RNFL in combination with further retinal measures will also be assessed by optical coherence tomography. Secondary outcome measures on brain MRI will include cortical volume, diffusion-weighted imaging, resting state functional MRI, MR spectroscopy and magnetisation transfer ratio. In addition, high and low contrast visual acuity, visual fields, colour vision and electrophysiology will be assessed alongside quality of life measures. Ethics and dissemination Ethical approval was given by the south central Oxford B research ethics committee (REC reference: 13/SC/0022). The findings

  16. Double-blind randomized study of lonidamine and radiotherapy in head and neck cancer

    SciTech Connect

    Magno, L.; Terraneo, F.; Bertoni, F.; Tordiglione, M.; Bardelli, D.; Rosignoli, M.T.; Ciottoli, G.B. )

    1994-04-30

    This Phase III double blind, placebo-controlled study was performed to evaluate whether lonidamine can increase the tumor control of radiotherapy in the treatment of advanced head and neck cancer without any synergistic toxic effects on the exposed normal tissues. Ninety-seven patients with Stages II-IV squamous cell carcinoma of the head and neck were enrolled. Separate analyses were done on the 96 eligible patients and the 90 patients who completed the prescribed treatment regimen. Patients received radiotherapy up to a planned total of 60-66 Gy, in 2 daily fractions of 1.5 Gy each and either lonidamine (450 mg p.o. in three divided daily doses) or placebo, given continuously for 3 months or up to 1 month after the end of radiotherapy. The rate of tumor clearance was 66% in the lonidamine group and 65% in the placebo group, while the subsequent failure rate was 50% and 77%, respectively. The 3 and 5 year locoregional control rates in the adequately treated patients achieving complete tumor clearance were 66% and 63% for lonidamine vs. 41% and 37% for placebo. The disease-free survival in adequately treated patients was significantly better in the lonidamine group, with 3 and 5 year rates of 44% and 40%, respectively, vs. 23% and 19% in the placebo group. The overall survival rate for all eligible patients at both 3 and 5 years was 44% in the lonidamine group and 44% and 31%, respectively, in the placebo group. Both acute and late radiation reactions were similar in the two groups. Myalgia and testicular pain were the most frequent side effects of lonidamine with an incidence of 8.5% and 4.2%, respectively. The addition of lonidamine to hyperfractionated radiotherapy was correlated with a statistically and clinically significant proportion of long-term disease-free patients. The toxicity of radiotherapy was not aggravated by the drug and the overall tolerance of the combined regimen was acceptable. 54 refs., 4 figs., 7 tabs.

  17. Mucolytic Effectiveness of Tyloxapol in Chronic Obstructive Pulmonary Disease - A Double-Blind, Randomized Controlled Trial

    PubMed Central

    Koppitz, Martin; Eschenburg, Charlotte; Salzmann, Emilia; Rosewich, Martin; Schubert, Ralf; Zielen, Stefan

    2016-01-01

    Objective Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD. Design A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol. Results A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34–5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73–3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure

  18. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial

    PubMed Central

    Rangaka, Molebogeng X; Wilkinson, Robert J; Boulle, Andrew; Glynn, Judith R; Fielding, Katherine; van Cutsem, Gilles; Wilkinson, Katalin A; Goliath, Rene; Mathee, Shaheed; Goemaere, Eric; Maartens, Gary

    2014-01-01

    Background Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Isoniazid preventive therapy (IPT), which decreases the risk of tuberculosis in people not on ART, may offer additional protection. Methods Pragmatic randomized double-blind placebo-controlled trial to evaluate the effect of 12 months IPT among participants established on or newly starting ART, in Khayelitsha, South Africa (NCT00463086, Lancet D-09-02885). Tuberculosis was excluded at screening by sputum culture. Incident tuberculosis was the primary endpoint. Findings 1,329 participants contributed 3,227 person-years (PY) of follow up in the modified intention-to-treat analysis; 662 on IPT and 667 on placebo. There were 95 incident tuberculosis cases: 2.3 (95%CI 1.6-3.1) versus 3.6 (95%CI 2.8-4.7) per 100 PY in the IPT and placebo arms respectively (hazard ratio 0.63, 95%CI 0.41-0.94). Study drug was discontinued due to grade 3 or 4 raised ALT in 19/662 in the IPT and 10/667 in the placebo arm, risk ratio=1.9 (95%CI 0.90-4.09). In secondary analyses, there was no evidence that the effect of IPT was restricted to those who were positive on tuberculin skin test (TST) or interferon gamma release assay (IGRA): adjusted hazard ratio for those with negative tests 0.43 (95%CI 0.21-0.86) and 0.43 (95%CI 0.20-0.96); for positive tests 0.86 (95%CI 0.37-2.00) and 0.55 (95%CI 0.26-1.24) respectively. No all cause mortality benefit of IPT was demonstrated Interpretation IPT reduced the incidence of tuberculosis in HIV-infected individuals on ART. In this high incidence setting, individuals on ART who have TST or IGRA negative results may also benefit from IPT. IPT can easily be implemented in ART clinics. PMID:24835842

  19. Double blind, cluster randomised trial of low dose supplementation with vitamin A or β carotene on mortality related to pregnancy in Nepal

    PubMed Central

    West, Keith P; Katz, Joanne; Khatry, Subarna K; LeClerq, Steven C; Pradhan, Elizabeth K; Shrestha, Sharada R; Connor, Paul B; Dali, Sanu M; Christian, Parul; Pokhrel, Ram P; Sommer, Alfred

    1999-01-01

    Objective To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A, either preformed or as β carotene. Design Double blind, cluster randomised, placebo controlled field trial. Setting Rural southeast central plains of Nepal (Sarlahi district). Subjects 44 646 married women, of whom 20 119 became pregnant 22 189 times. Intervention 270 wards randomised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo, vitamin A (7000 μg retinol equivalents) or β carotene (42 mg, or 7000 μg retinol equivalents) for over 3½ years. Main outcome measures All cause mortality in women during pregnancy up to 12 weeks post partum (pregnancy related mortality) and mortality during pregnancy to 6 weeks postpartum, excluding deaths apparently related to injury (maternal mortality). Results Mortality related to pregnancy in the placebo, vitamin A, and β carotene groups was 704, 426, and 361 deaths per 100 000 pregnancies, yielding relative risks (95% confidence intervals) of 0.60 (0.37 to 0.97) and 0.51 (0.30 to 0.86). This represented reductions of 40% (P<0.04) and 49% (P<0.01) among those who received vitamin A and β carotene. Combined, vitamin A or β carotene lowered mortality by 44% (0.56 (0.37 to 0.84), P<0.005) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births, or by 40% (P<0.02). Differences in cause of death could not be reliably distinguished between supplemented and placebo groups. Conclusion Supplementation of women with either vitamin A or β carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural, undernourished populations of south Asia. Key messagesMaternal vitamin A deficiency, evident as night blindness or low serum retinol concentration during pregnancy, is widely prevalent in rural south AsiaIn Nepal, women of

  20. Efficacy and cost-effectiveness of a physiotherapy program for chronic rotator cuff pathology: A protocol for a randomised, double-blind, placebo-controlled trial

    PubMed Central

    Bennell, Kim; Coburn, Sally; Wee, Elin; Green, Sally; Harris, Anthony; Forbes, Andrew; Buchbinder, Rachelle

    2007-01-01

    Background Chronic rotator cuff pathology (CRCP) is a common shoulder condition causing pain and disability. Physiotherapy is often the first line of management for CRCP yet there is little conclusive evidence to support or refute its effectiveness and no formal evaluation of its cost-effectiveness. Methods/Design This randomised, double-blind, placebo-controlled trial will involve 200 participants with CRCP recruited from medical practices, outpatient departments and the community via print and radio media. Participants will be randomly allocated to a physiotherapy or placebo group using concealed allocation stratified by treating physiotherapist. Both groups will receive 10 sessions of individual standardised treatment over 10 weeks from one of 10 project physiotherapists. For the following 12 weeks, the physiotherapy group will continue a home exercise program and the placebo group will receive no treatment. The physiotherapy program will comprise shoulder joint and spinal mobilisation, soft tissue massage, postural taping, and home exercises for scapular control, posture and rotator cuff strengthening. The placebo group will receive inactive ultrasound and gentle application of an inert gel over the shoulder region. Blinded assessment will be conducted at baseline and at 10 weeks and 22 weeks after randomisation. The primary outcome measures are self reported questionnaires including the shoulder pain and disability index (SPADI), average pain on an 11-point numeric rating scale and participant perceived global rating of change. Secondary measures include Medical Outcomes Study 36-item short form (SF-36), Assessment of Quality of Life index, numeric rating scales for shoulder pain and stiffness, participant perceived rating of change for pain, st