Analyzing Female Trauma Exposed Responses to a Medication
Condition: Stress Disorders, Post-traumatic
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

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
    

Intervention name(s): GSK561679; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): GSK561679, oral administration, 350mg/day, 6 week administration; Placebo compound treatment for comparison with IP
Other intervention name(s): CRF1 antagonist; Sugar pill
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Stress disorders, Post-traumatic; Sleep