Clinical trial NCT01814332
Conditions: Stress Disorders, Post-traumatic
Keywords: Stress disorders, Post-traumatic Sleep
Sponsor: VA Office of Research and Development
Start date: 2010-01-01; Completion date: 2014-10-31
Enrollment: 128 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This purpose of this study is to look at the safety of the experimental drug GSK561679 as well as its effects on PTSD symptoms, thinking and memory, startle reaction, stress hormones, and mental health symptoms in comparison to placebo (an inactive substance).

Detailed description:
A growing body of literature suggests that stress-related disorders such as PTSD are associated with chronically increased activity of CNS circuits that utilize corticotropin-releasing factor (CRF), a neuropeptide involved in mediating the neuroendocrine, immune, autonomic, and behavioral responses to stress. CRF1 receptor antagonists exert significant dampening effects on this system, but have never been investigated in patients with PTSD. The investigators at Mount Sinai School of Medicine (MSSM) and the National Institute of Mental Health (NIMH) Intramural Research Program have conducted a Phase II proof-of-concept clinical trial of a neurokinin-1 antagonist provided by GlaxoSmithKline (GSK). In this investigation, we will conduct a 2-site (Emory and MSSM), 6-week, randomized, double-blind, placebo-controlled, parallel-arm, fixed dose trial evaluating the efficacy, safety, and tolerability of GSK561679 for 154 female adult outpatients with PTSD. The San Francisco Department of Veterans Affairs Medical Center (SFVAMC) was added as a site in July 2012. SFVAMC will enroll 40 female adult outpatients with PTSD.

We propose to investigate the efficacy of the highly specific CRF1 antagonist GSK561679 in PTSD in a placebo-controlled clinical trial. GSK561679 has not been approved by the Food and Drug Administration for the treatment of any condition. Furthermore, we propose to longitudinally investigate whether certain biological surrogate markers (neuroendocrine, neurophysiology, genotyping) are predictive of treatment response. If a patient is already taking medication for PTSD and has achieved therapeutic response, she will not be tapered off effective medication(s) to participate in this study, and will not be eligible for the study. Taper and discontinuation of medications in preparation for this study will only occur in those patients who are not responding to medication treatment for PTSD.

Preclinical and clinical literature also exists which implicates both hypothalamic and extra hypothalamic CRF in stress-related insomnia and the regulation of non-rapid eye movement delta sleep. There is preliminary evidence that blocking CRF signaling results in an immediate improvement in stress-related sleep disturbances. Disturbed sleep is the most prevalent symptom endorsed by PTSD patients. It is potentially debilitating in many domains of functioning, and it is an outcome that can be objectively and precisely measured with sleep EEG. Therefore, an exploratory aim of this study will be to investigate the impact of GSK561679 on objective measures of sleep continuity and quantitative sleep EEG using ambulatory polysomnography. All subjects enrolled at SFVAMC who meet inclusion and exclusion criteria for the study will be given the option of having their sleep monitored throughout the study

Arms: arm 1: GSK561679, oral administration, 350mg/day, 6 week administration arm 2: Placebo compound treatment for comparison with IP
Interventions: intervention 1: GSK561679 intervention 2: Placebo
Intervention descriptions: intervention 1: GSK561679, oral administration, 350mg/day, 6 week administration intervention 2: Placebo compound treatment for comparison with IP

Protocol documents: