Posttraumatic Stress Disorder (PTSD) is a serious and debilitating condition, occurring in 7% of the general population and 15 to 20% among persons exposed to highly intense trauma such as sexual assault and combat. Currently available treatments with antidepressants, anticonvulsants or exposure-based cognitive therapies may not be universally effective.
Preclinical and clinical evidence suggests that low levels of the neurosteroid allopregnanolone (ALLO), a metabolite of progesterone, contribute to the pathophysiology of PTSD. ALLO is a potent modulator of brain gamma-amino-butyric acid (GABA) inhibitory receptors and has anxiety-reducing, sedative, anticonvulsant, and neuroprotective effects. ALLO levels have been related to PTSD or PTSD-like symptom severity and treatment response in human and animal studies. Direct replacement of ALLO would thus seem to be a promising and novel way to treat PTSD. However, ALLO is not orally bioavailable, and produces active steroid metabolites that are potentially of concern for long term treatment.
Ganaxolone is a modified, synthetic version of ALLO with similar pharmacological and behavioral effects, good bioavailability, and no signal for tolerance. Therefore, ganaxolone is among the first commercially viable neurosteroid treatments and is furthest along in development as a potential FDA-approved medication. Ganaxolone has been studied so far in epilepsy and has demonstrated good tolerability and safety in >900 subjects.
The primary objective of this study is to assess the efficacy of ganaxolone compared to placebo (a sugar pill) in the treatment of PTSD in men and women aged 18 to 55. Specifically, the study will determine whether or not ganaxolone works better than placebo in reducing PTSD symptoms measured by the Clinician-Administered PTSD Scale (CAPS) over 6 weeks of treatment. The second objective is to evaluate the safety and tolerability of ganaxolone in patients with PTSD.
Seven INTRuST Consortium clinical trial centers will treat approximately 120 subjects. Half of the participants will be randomized to treatment with ganaxolone for 6 weeks, after which the participants will continue ganaxolone for an additional 6 weeks before a one-week medication taper. The other half of the participants will be randomized to placebo for the first 6 weeks and then cross over to ganaxolone for the next 6 weeks before a one-week taper. Neither the participant nor study personnel will know if the participant is on ganaxolone or placebo during the first 6 weeks (though this can be found out if necessary for safety reasons). In general, participants will be scheduled for 10 every other week reimbursed study visits over the course of about 17 weeks.
This study may provide evidence for a new, safe, effective medication for the treatment of PTSD.