A Phase 1b Safety Study of SER-287, a Spore-Based Microbiome Therapeutic, for Active Mild to Moderate Ulcerative Colitis.

Background & Aims: Firmicutes bacteria produce metabolites that maintain the intestinal barrier and mucosal immunity. Firmicutes are reduced in the intestinal microbiota of patients with ulcerative colitis (UC). In a phase 1b trial of patients with UC, we evaluated the safety and efficacy of SER-287, an oral formulation of Firmicutes spores, and the effects of vancomycin preconditioning on expansion (engraftment) of SER-287 species in the colon.

Use of a post-sleep questionnaire-interactive voice response system (PSQ-IVRS) to evaluate the subjective sleep effects of ramelteon in adults with chronic insomnia.

Objective: Ramelteon is an MT(1)/MT(2) melatonin receptor agonist approved in the US and Japan for the treatment of sleep-onset insomnia. This study evaluated the effects of ramelteon 8mg on patient reported sleep parameters in adults with chronic insomnia in an at-home setting using a post-sleep questionnaire-interactive voice response system (PSQ-IVRS).

Methods: Adults aged 18-64 years with chronic insomnia were randomized to receive ramelteon 8 mg or placebo nightly for 3weeks.

Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel.

Objective: Ramelteon, an MT(1)/MT(2) melatonin receptor agonist, was evaluated for its ability to reduce sleep-onset difficulties associated with eastward jet travel.

Methods: Healthy adults (n=110) with a history of jet lag sleep disturbances were flown eastward across five time zones from Hawaii to the east coast of the US. Ramelteon 1, 4, or 8 mg or placebo was administered 5 min before bedtime (local time) for four nights.

Effects of ramelteon 8 mg on objective sleep latency in adults with chronic insomnia on nights 1 and 2: pooled analysis.

Objective: Ramelteon is an MT(1)/MT(2) melatonin receptor agonist indicated for the treatment of insomnia characterized by difficulty with sleep onset. In previous clinical studies, ramelteon reduced latency to persistent sleep (LPS) in subjects with chronic insomnia. The goal of the current analysis was to determine the average reduction in LPS and overall adverse event profile for subjects taking ramelteon 8 mg.

Effect of ramelteon on middle-of-the-night balance in older adults with chronic insomnia.

Study Objectives: To evaluate the effect of ramelteon on middle-of-the-night balance, mobility, and memory in older insomniacs.

Methods: Thirty-three older adults (age > or = 65 years) with insomnia were enrolled in a single-dose, 3-way crossover study of balance after bedtime administration of ramelteon, 8 mg; zolpidem, 10 mg (positive control); or placebo. Subjects were administered study medication 30 minutes before bedtime and were awakened 2 hours after dosing to evaluate balance (Sensory Organization Test), turning speed and stability, memory (immediate and delayed word recall), and adverse events.

Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia.

Study Objectives: Long-duration (> or = 6 months) polysomnographic studies of insomnia medications are lacking. This study evaluated the long-term efficacy of ramelteon, a selective MT1/MT2 melatonin-receptor agonist used for insomnia treatment.

Design: Six-month, randomized, double-blind, placebo-controlled study.

Safety and subjective sleep effects of ramelteon administration in adults and older adults with chronic primary insomnia: a 1-year, open-label study.

Objective: To evaluate the long-term safety and subjective sleep effects of ramelteon in adults with chronic insomnia.

Method: Subjects with primary insomnia (DSM-IV-TR criteria) for >or= 3 months received ramelteon nightly for 1 year; a 3-day placebo run out followed. Subjects aged >or=65 years received open-label ramelteon 8 mg (N = 248); those aged 18 to 64 years received ramelteon 16 mg (N = 965).

Effects of long-term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomnia.

Objective: To evaluate the effects of ramelteon, an MT(1)/MT(2) melatonin receptor agonist used to treat insomnia, on endocrine function in adults with chronic insomnia.

Methods: This was a double-blind, placebo-controlled, trial of adults (18-45 years) with chronic insomnia. Subjects received either ramelteon 16 mg or placebo nightly for 6 months.

Circadian phase-shifting effects of repeated ramelteon administration in healthy adults.

Study Objectives: To assess the ability of repeated daily oral ramelteon to facilitate re-entrainment of human circadian rhythms after an imposed phase advance of the sleep-wake cycle.

Methods: A total of 75 healthy adult volunteers aged 18-45 years remained in a sleep laboratory for 6 days and 5 nights; a 5-h phase advance in their sleep-wake cycle was imposed under dim-light conditions. Oral ramelteon (1,2, 4, or 8 mg once daily for 4 days) or placebo was administered 30 min before bedtime.

Ramelteon 8 mg/d versus placebo in patients with chronic insomnia: post hoc analysis of a 5-week trial using 50% or greater reduction in latency to persistent sleep as a measure of treatment effect.

Background: Ramelteon is a selective MT1/MT2 melatonin receptor agonist approved by the US Food and Drug Administration for insomnia treatment.

Objective: The aim of this post hoc analysis was to compare the efficacy and tolerability of ramelteon 8 mg/d versus placebo in adults with chronic insomnia.

Methods: This study analyzed data from a previously published 5-week, randomized, double-blind, placebo-controlled study.

The effects of ramelteon in a first-night model of transient insomnia.

Objective: To evaluate the efficacy and safety of ramelteon, a highly selective MT(1)/MT(2) melatonin receptor agonist, for the treatment of transient insomnia in adults.

Methods: In a randomized, double-blind, placebo-controlled, multi-center study, 289 adults naive to a sleep laboratory environment were randomized to receive a single nighttime dose of ramelteon 8 mg, 16 mg, or placebo. The primary variable was latency to persistent sleep measured by polysomnography.

Use of computerized dynamic posturography to assess balance in older adults after nighttime awakenings using zolpidem as a reference.

Background: Computerized dynamic posturography (CDP) has been used to detect balance and stability impairments in adults of all ages. The goal of the current pilot study was to evaluate balance in healthy older adults after a middle-of-the-night awakening and to assess the ability of CDP to measure effects of bedtime zolpidem administration.

Methods: Two studies used CDP to evaluate balance in healthy older adults (> or = 65 years) during middle-of-the-night awakenings.

The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease.

Background: Individuals with moderate to severe chronic obstructive pulmonary disease (COPD) have poor sleep quality. This study evaluated the effects of ramelteon, an MT(1)/MT(2) melatonin receptor agonist indicated for insomnia treatment on respiration in this population.

Materials And Methods: This double-blind, crossover study enrolled 25 subjects (>or=40 years) with moderate to severe COPD (FEV(1)/FVC <70% and FEV(1) between 50 and 80% of predicted value [moderate], or FEV(1)/FVC <70% and FEV(1) <50% of predicted value [severe]).

Effect of ramelteon, a selective MT(1)/MT (2)-receptor agonist, on respiration during sleep in mild to moderate COPD.

Ramelteon, a selective MT(1)/MT(2) melatonin receptor agonist, was evaluated in subjects with mild to moderate chronic obstructive pulmonary disease (COPD) to determine whether it would have a negative effect on measures of safety and respiration. This randomized, double-blind, crossover study in 26 subjects with mild to moderate COPD compared the effects of a single bedtime dose of ramelteon 16 mg and placebo on sleep, oxygenation, and sleep-related abnormal breathing events. Compared with placebo, ramelteon had no statistically significant effect on mean arterial oxygen percent saturation (SaO(2)) for the entire night (92.

Self-reported efficacy and tolerability of ramelteon 8 mg in older adults experiencing severe sleep-onset difficulty.

Background: Ramelteon is a selective MT(1)/MT(2) melatonin receptor agonist indicated for the treatment of insomnia characterized by difficulty with sleep onset.

Objective: The current analysis was conducted to determine the effectiveness of ramelteon 8 mg in reducing the time to fall asleep in older adults with severe baseline sleep-onset difficulties.

Methods: Patients with severe sleep-onset difficulty (defined as subjective sleep latency [sSL] > or =60 minutes) who had received ramelteon 8 mg or placebo were selected from a previously published multicenter outpatient trial of 829 older adults (aged > or =65 years) with primary, chronic insomnia (according to Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] criteria).

Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia.

Objective: To evaluate efficacy and safety of ramelteon (MT1/MT2-receptor [corrected] agonist) in subjects with chronic primary insomnia.

Methods: Randomized, multicenter, double-blind, placebo-controlled trial of nightly ramelteon treatment (8 mg or 16 mg) in adults (N=405) with primary chronic insomnia (DSM-IV-TR). Latency to persistent sleep (LPS), TST, sleep efficiency, wake time after sleep onset, and number of awakenings were measured by polysomnography.

A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia.

Objective: To assess the efficacy and safety of ramelteon, a selective melatonin MT1/MT2-receptor agonist, for insomnia treatment in older adults.

Methods: In a randomized, 9-week, 3-period crossover trial conducted at 17 sleep centers, older adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age [range], 70.7 [65-83] years) were administered placebo, ramelteon 4 mg, and ramelteon 8 mg in three treatment phases for two consecutive nights.

Safety of ramelteon in individuals with mild to moderate obstructive sleep apnea.

Ramelteon is a selective MT(1)/MT(2)-receptor agonist indicated for insomnia treatment. Because it has no depressant effects on the nervous system, it is not expected to affect the control of breathing. The potential effects of ramelteon on apneic and hypopneic events and arterial oxygen saturation (SaO(2)) in individuals with obstructive sleep apnea were assessed.

Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia.

Background And Purpose: To assess the efficacy and safety of ramelteon, a selective MT(1)/MT(2) receptor agonist, for chronic insomnia treatment.

Patients And Methods: Randomized, double-blind, placebo-controlled 35-night outpatient trial with weekly clinic visits at multiple centers. Patients include older adults (>or=65 years; N=829) with chronic insomnia.

In vivo assessment of human vaginal oxygen and carbon dioxide levels during and post menses.

Previous in vitro and in vivo animal studies showed that O(2) and CO(2) concentrations can affect virulence of pathogenic bacteria such as Staphylococcus aureus. The objective of this work was to measure O(2) and CO(2) levels in the vaginal environment during tampon wear using newly available sensor technology. Measurements by two vaginal sensors showed a decrease in vaginal O(2) levels after tampon insertion.

Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation.

Monoclonal antibody (MAb) technology was used to examine aggrecan metabolites and the role of aggrecanases and matrix metalloproteinases (MMPs) in proteolysis of the interglobular domain (IGD) and C-terminus of aggrecan. An in vitro model of progressive cartilage degradation characterized by early proteoglycan loss and late stage collagen catabolism was evaluated in conjunction with a broad-spectrum inhibitor of MMPs. We have for the first time demonstrated that IGD cleavage by MMPs occurs during this late stage cartilage degeneration, both as a primary event in association with glycosaminoglycan (GAG) release from the tissue and secondarily in trimming of aggrecanase-generated G1 metabolites.