Project description:Revefenacin is a once-daily long-acting muscarinic antagonist (LAMA) in clinical development for the treatment of patients with chronic obstructive pulmonary disease (COPD). In a dose-ranging study, nebulized once-daily revefenacin had a long duration of action in patients after 7 days' administration of doses up to 700 ?g. In this multiple-dose study, the bronchodilation efficacy and adverse events profile were characterized in patients administered nebulized revefenacin once daily for 28 days.A total of 355 COPD patients (mean age 62 years, mean forced expiratory volume in 1 s [FEV1] 44% of predicted) were randomized in a double-blind, placebo-controlled parallel group study. Inhaled corticosteroids as well as short-acting bronchodilators were permitted. Once-daily treatments (44, 88, 175 or 350 ?g revefenacin or matching placebo) were administered by a standard jet nebulizer, for 28 days. The primary endpoint was change from baseline in D28 trough FEV1, and secondary endpoints included weighted mean FEV1 over 0 to 24 h and rescue medication (albuterol) use. Safety evaluations included adverse events, laboratory assessments, electrocardiograms and 24-h Holter profiles.Revefenacin (88, 175 and 350 ?g) significantly improved D28 trough FEV1 over placebo (187.4, 166.6 and 170.6 mL, respectively, all p < 0.001); 44 ?g produced a sub-therapeutic response. At doses ?88 ?g, more than 80% of patients achieved at least a 100-mL increase from baseline FEV1 in the first 4 h post dose compared with 33% of placebo patients. For doses ?88 ?g, D28 24 h weighted mean differences from placebo for FEV1 were numerically similar to respective trough FEV1 values, indicating bronchodilation was sustained for 24 h post dose. Doses ?88 ?g reduced the average number of albuterol puffs/day by more than one puff/day. The 350 ?g dose did not demonstrate additional efficacy over that observed with 175 ?g revefenacin. Revefenacin was generally well tolerated, with minimal reports of systemic anti-cholinergic effects.These data suggest that 88 and 175 ?g revefenacin are appropriate doses for use in longer-term safety and efficacy trials. Revefenacin offers the potential for the first once-daily LAMA for nebulization in patients with COPD who require or prefer a nebulized drug delivery option.ClinicalTrials.gov NCT02040792 . Registered January 16, 2014.

Project description:Hops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m(2), classified as "obese level 1" in Japan or as "overweight" by the WHO.A randomized, double-blind, placebo-controlled parallel group study.Two hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m(2)) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks.Compared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group.The present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects.UMIN-CTR UMIN000014185.

Project description:BACKGROUND:Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. METHODS:A pilot clinical trial using 140?mg oral AP or placebo twice daily for 24?months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. RESULTS:Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was -?0.679% for the AP group and?-?1.069% for the placebo group (mean difference: -0.39; 95% CI [-?0.836-0.055], p?=?0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p?=?0.06). The mean EDSS change was -?0.025 in the AP group and?+?0.352 in the placebo group (mean difference: 0.63, p?=?0.042). Adverse events related to AP were mild rash and dysgeusia. CONCLUSIONS:AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. TRIAL REGISTRATION:ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.

Project description:Although prefrontal brain impairments are one of the best-replicated brain imaging findings in relation to aggression, little is known about the causal role of this brain region. This study tests whether stimulating the dorsolateral prefrontal cortex using transcranial direct current stimulation (tDCS) reduces the likelihood of engaging in aggressive acts, and the mechanism underlying this relationship. In a double-blind, stratified, placebo-controlled, parallel-group, randomized trial, 81 human adults (36 males, 45 females) were randomly assigned to an active (N = 39) or placebo (N = 42) condition, and then followed up 1 d after the experiment session. Intentions to commit aggressive acts and behavioral aggression were assessed using hypothetical vignettes and a behavioral task, respectively. The secondary outcome was the perception of the moral wrongfulness of the aggressive acts. Compared with the sham controls, participants who received anodal stimulation reported being less likely to commit physical and sexual assault (p < 0.01). They also judged aggressive acts as more morally wrong (p < 0.05). Perceptions of greater moral wrongfulness regarding the aggressive acts accounted for 31% of the total effect of tDCS on intentions to commit aggression. Results provide experimental evidence that increasing activity in the prefrontal cortex can reduce intentions to commit aggression and enhance perceptions of the moral wrongfulness of the aggressive acts. Findings shed light on the biological underpinnings of aggression and theoretically have the potential to inform future interventions for aggression and violence.SIGNIFICANCE STATEMENT Aggressive behaviors pose significant public health risks. Understanding the etiology of aggression is paramount to violence reduction. Investigations of the neural basis of aggression have largely supported correlational, rather than causal, interpretations, and the mediating processes underlying the prefrontal-aggression relationship remain to be well elucidated. Through a double-blind, stratified, placebo-controlled, parallel-group, randomized trial, this study tested whether upregulation of the prefrontal cortex reduces the likelihood of engaging in aggression. Results provide experimental evidence that increasing prefrontal cortical activity can reduce intent to commit aggressive acts. They also shed light on moral judgment as one mechanism that may link prefrontal deficits to aggression and, in theory, have the potential to inform future approaches toward reducing aggression.

Dataset Information

The Effect of Aclidinium on Symptoms Including Cough in Chronic Obstructive Pulmonary Disease: A Phase 4, Double-Blind, Placebo-controlled, Parallel-Group Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure