A Randomized Clinical Trial of Mifepristone in PTSD
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|ClinicalTrials.gov Identifier: NCT01946685|
Recruitment Status : Unknown
Verified March 2015 by Julia A. Golier, M.D., James J. Peters Veterans Affairs Medical Center.
Recruitment status was: Recruiting
First Posted : September 19, 2013
Last Update Posted : April 1, 2015
Posttraumatic stress disorder (PTSD) is a common and disabling psychiatric disorder. Left untreated or under-treated, it can become a chronic condition associated with significant distress, depression, aggression, family disruption, and substance abuse. There is also accumulating evidence that combat-related PTSD is associated with an increased risk of morbidity and mortality. For the welfare of returning veterans with PTSD and their families, it is critical that this disorder is promptly identified and effectively treated. Considerable advances that have been made in the assessment and 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. Thus, blockade of the GR receptor with mifepristone may target unique aspects of PTSD and lead to clinically meaningful improvement in symptoms and cognition. There is preliminary 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). That there can be sustained clinical and neuropsychological effects of mifepristone and normalization of basal HPA axis activity after drug discontinuation in these disorders, has led to the view that mifepristone's actions include recalibration of a dysregulated HPA axis. Accordingly, we propose to study the effects of mifepristone in veterans with chronic PTSD to determine if it is efficacious in improving PTSD symptoms and associated clinical outcomes. To better understand the mechanism of action of mifepristone we propose to assess the effects of mifepristone on HPA axis activity and their relationship to treatment outcome and clinical response.
To achieve these objectives, we propose to conduct a Phase IIa, multi-site, double-blind, placebo controlled trial of mifepristone in veteran outpatients with military-related PTSD through the VA's Cooperative Clinical Trial Award program. We propose to enroll 136 unmedicated male veterans with military related PTSD at four VA sites (Albuquerque, NM, Bronx, NY, Durham, NC, and San Diego, CA). Eligible veterans will be randomly assigned in parallel groups to treatment with 600 mg/day mifepristone or placebo for one week and followed for up to three months. Using statistical selection theory, we propose to determine whether 600 mg of mifepristone yields a sufficiently high proportion of clinical responders after one month to warrant more extensive and definitive research as part of a Phase III trial. Secondarily, we seek to determine the effect of the dose of mifepristone compared to placebo on the trajectory of CAPS scores and the time to addition of rescue medication, as well as compare rates of adverse events and serious adverse events across the three groups. We 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 ACTH levels to clinical response and the time to addition of rescue medications.
|Condition or disease||Intervention/treatment||Phase|
|PTSD||Drug: 600 mg/day Mifepristone Drug: Placebo||Phase 2|
Novel approaches to the treatment of post traumatic stress disorder (PTSD) in veterans are urgently needed. This proposal seeks to test an innovative approach, one that involves careful pharmacological manipulation of the body's major stress system, the hypothalamic-pituitary-adrenal (HPA) axis, using the dose level of the FDA-approved drug, mifepristone (600 mg/day).
We therefore seek to examine the effects of glucocorticoid receptor antagonist, mifepristone (Mifeprex®), on clinical and cognitive outcomes in veterans with posttraumatic stress disorders.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||136 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Novel Therapeutics in PTSD: A Randomized Clinical Trial of Mifepristone|
|Study Start Date :||November 2012|
|Estimated Primary Completion Date :||November 2015|
|Estimated Study Completion Date :||June 2016|
Experimental: 600 mg/day Mifepristone
600 mg/day Mifepristone for 7 days
|Drug: 600 mg/day Mifepristone|
Placebo Comparator: Placebo
No active treatment by intervention, supportive treatment avaialble.
- CAPS score [ Time Frame: Four Weeks ]The primary clinical outcome measure will be the presence or absence of a clinical response, defined as a 30% or greater reduction in total CAPS (past week symptom status) score from baseline to four weeks
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01946685
|United States, New York|
|James J. Peters VA Medical Center||Recruiting|
|Bronx, New York, United States, 10468|
|Contact: Kirklyn Escondo 718-584-9000 ext 6567 firstname.lastname@example.org|
|Study Chair:||J Golier, MD||James J. Peters Veterans Affairs Medical Center|