Phase 2
N=81
Novel Therapeutics in Posttraumatic Stress Disorder (PTSD): A Randomized Clinical Trial of Mifepristone
Stress Disorders, Post-Traumatic
Bottom Line
View on ClinicalTrials.gov: NCT01739335 ↗Enrolled (actual)
81
Serious AEs
1.2%
Results posted
Jan 2018
Primary outcome: Primary: Percentage of Clinical Responders at 4-week Follow-up — 15; 12; 24; 26 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Mifepristone Oral Tablet [Korlym] (Drug); Placebo Oral Tablet (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- VA Office of Research and Development
- Primary completion
- Sep 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Clinical Responders at 4-week Follow-up |
15; 12; 24; 26 | — |
| SECONDARY Percentage of Clinical Responders at 12-week Follow-up (End of Study) |
10; 14; 22; 21 | — |
| SECONDARY Change in CAPS Total Score From Baseline to 4-week and 12-week |
-13.96; -15.83; -15.15; -18.06 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Participant is a male veteran.
- Veteran meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnostic criteria for chronic PTSD.
- Veteran has a CAPS total score (past month symptom status) greater than or equal to 50 at screening.
- For veterans taking psychotropic medications (i.e., antidepressants, antipsychotics or anxiolytics/sedative-hypnotics), the veteran will be on a stable dose for at least five weeks prior to screening.
- For veterans not taking psychotropic medication, a minimum of five half-lives must elapse prior to screening since the veteran last took any given psychotropic medication.
Exclusion Criteria
- Veteran recently continued to engage in a maladaptive pattern of alcohol/substance use and/or abuse (as defined in protocol).
- Veteran has used potent CYP3A4 inhibitors (fluconazole, ketoconazole, itraconazole, erythromycin, rifampin) and inducers within five half-lives prior to randomization.
- Veteran is taking simvastatin, lovastatin, fentanyl, pimozide, bupropion, nefazodone, dihydroergotamine, ergotamine, quinidine, sirolimus, tacrolimus, or clarithromycin, cyclosporine, St. John's Wort, diltiazem, verapamil, propranolol, alprazolam, carvedilol or some anticonvulsants (phenytoin, phenobarbital, or carbamazepine) within five half-lives prior to randomization.
- Veteran is taking oral corticosteroids within five half-lives prior to randomization.
- Veteran should be free of a major medical illness and medical condition that contraindicate the administration of mifepristone. These include but are not limited to:
- Veteran has a history of adrenal insufficiency or a low plasma cortisol level at screening (a.m. level less than 5 mcg/dl or a p.m. level of less than 3 mcg/dl.)
- Veteran has a history of severe traumatic brain injury, a history of a stroke, or another neurological illness or injury likely to impact cognitive functioning.
- Veteran has diabetes mellitus, an endocrinopathy, or another major medical illness.
- Veteran has a history of cardiovascular disease including a history of angina, myocardial infarction or other evidence of coronary artery disease, or congestive heart failure.
- Veteran has prolonged QTc interval >450 msec on ECG at screening.
- Veteran has hypokalemia at screening (defined as potassium level < 3.5 Milliequivalent Per Liter (mEq/L)).
- Veteran has a history of hepato-biliary disease or an aspartate transaminase (AST), alanine transaminase (ALT) greater than 2 times the Upper Limit of Normal (ULN).
- Veteran has a history of renal disease or an estimated glomerular filtration rate (GFR) of < 60 ml/min.
- Veteran has a lifetime diagnosis of schizophrenia, schizoaffective disorder, or type I bipolar disorder.
- Veteran has a history of attempted suicide within the previous two years or active suicidal ideation within the past month as assessed by the Columbia-Suicide Severity Rating Scare (C-SSRS).
- Veteran is currently receiving specialized trauma-focused psychotherapy, such as prolonged exposure therapy and cognitive processing therapy.
- Veteran is not willing to use effective means of birth control during the study.
- Veteran has a history of allergic reaction to mifepristone.
- Veteran is found to be unsuitable for study participation at the discretion of the site investigator for any reason.
Data sourced from ClinicalTrials.gov (NCT01739335). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.