Novel Therapeutics in Posttraumatic Stress Disorder (PTSD): A Randomized Clinical Trial of Mifepristone
Status:
Completed
Trial end date:
2016-11-16
Target enrollment:
Participant gender:
Summary
Posttraumatic stress disorder (PTSD) is a common and disabling psychiatric disorder for
Veterans. Left untreated or under-treated, it can become a chronic condition associated with
significant distress, depression, aggression, family disruption, substance abuse and an
increased risk of morbidity and mortality. Considerable advances were made in the treatment
of PTSD in recent years; however, psychopharmacological treatments have been shown to be
largely ineffective for Veterans with PTSD.
To address this gap, this proposal seeks to test an innovative treatment approach in PTSD -
pharmacological manipulation of the body's major stress system (the
hypothalamic-pituitary-adrenal (HPA) axis) with mifepristone. At high doses mifepristone is a
glucocorticoid receptor (GR) antagonist with peripheral and central nervous system effects,
making it a compound of interest in the treatment of stress related disorders. There is
abundant evidence of enhanced GR sensitivity in Veterans with PTSD which is thought to
underlie some of the symptoms of PTSD and associated disturbances in mood and cognition.
There is also evidence that short-term mifepristone treatment has sustained beneficial
effects on mood, cognition and sleep disturbance in some neuropsychiatric conditions (major
depression, bipolar disorder, primary insomnia). The purpose of the study is to examine the
effects of mifepristone to determine if it is efficacious in improving PTSD symptoms and
associated clinical outcomes.
To achieve these objectives, the investigators propose to conduct a Phase IIa, multi-site,
double-blind, placebo controlled trial of mifepristone in male Veteran outpatients with
chronic PTSD through the VA's Cooperative Clinical Trial Award program. The investigators
propose to enroll 90 subjects at multiple VA sites based on an estimated attrition rate of
20%. Eligible Veterans will be randomly assigned to the treatment of mifepristone (600
mg/day) or placebo for one week and followed for up to three months. The investigators will
also describe the effects of mifepristone on several other clinical parameters including PTSD
symptomology, depression severity, sleep quality, and functional impairment. Several measures
of neuroendocrine functioning will also be obtained to explore the relationship of plasma
cortisol and adrenocorticotropic hormone (ACTH) levels to clinical response and the time to
addition of rescue medications.
Phase:
Phase 2
Details
Lead Sponsor:
James J. Peters Veterans Affairs Medical Center VA Office of Research and Development
Collaborators:
Durham VA Medical Center San Diego Veterans Healthcare System