NCT00659230

Nepicastat for Posttraumatic Stress Disorder (PTSD) in OIF/OEF Veterans

A Randomized, Placebo-Controlled Trial of the Dopamine-B-Hydroxylase (DBH) Inhibitor, Nepicastat, for the Treatment of PTSD in OIF/OEF Veterans

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: Tuscaloosa Research & Education Advancement Corporation · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Accepted

Summary

This study proposes a multi-site, randomized, double-blind, placebo-controlled clinical trial of the dopamine-ß-hydroxylase (DBH) inhibitor, nepicastat, for the treatment of posttraumatic stress disorder (PTSD) in outpatients who have previously served in a combat zone during Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF)or other Southwest conditions since 19800. A DBH inhibitor's mechanism of action is to decrease neuronal noradrenaline (NA) release by inhibiting DBH conversion of dopamine (DA) to NA. Animal models of PTSD and human studies have found a substantial increase in NA activity for these animal models and for PTSD in humans. Furthermore, recent clinical studies have improved PTSD hyper-arousal symptoms by reducing the NA over-activity using agents like NA post-synaptic antagonists. Key support for the proposed study is based on a similar improvement in PTSD symptoms after treatment with the DBH inhibitor, disulfiram. In the experience of the clinical investigators, the most common chief complaint of the OIF/OEF veterans with PTSD is hyperarousal (DSM-IV criterion D symptom cluster). These symptoms significantly interfere with social, occupational, and interpersonal function. Standard treatments with antidepressants are not fully effective in treating the symptoms of PTSD in veterans; thus, new treatments are needed. An intervention, such as nepicastat, aimed at reducing hyperarousal, as well as other PTSD symptoms, would have significant impact of restoring overall function and quality of life in OIF/OEF veterans with PTSD. Since hyperarousal symptoms responded relatively quickly to medications of this type, our study in 120 outpatient veterans with PTSD will compare nepicastat 120 mg/day vs. placebo in a 6-week double-blind, randomized clinical trial (RCT). The veterans will be followed for an additional 8 weeks after the RCT, during which, those who have a priori defined positive clinical response to the study medication, nepicastat vs. placebo, will be continued on the study medication, in order to assess further improvement and safety. Those patients who do not have a positive clinical response during the 6 week RCT will be offered the addition of the standard first-line PTSD pharmacotherapy, paroxetine, during the 8 weeks extension phase. Thus, weeks 7-14 offer an opportunity to evaluate longer-term nepicastat efficacy and to compare the treatment response of nonresponders after augmentation with paroxetine.

Detailed description

HYPOTHESES Primary Hypothesis: Compared to placebo treatment, nepicastat-treated OIF/OEF veterans with PTSD will have significantly reduced PTSD hyperarousal symptoms as defined by the Clinician Administered PTSD Scale \[CAPS\], subscale D (CAPS-D). Secondary Hypotheses: Compared to placebo, nepicastat-treated OIF/OEF veterans with PTSD will have: * Significantly reduced PTSD symptoms (total CAPS) * Significantly reduced PTSD reexperiencing symptoms (CAPS-B) * Significantly reduced PTSD avoidance symptoms (CAPS-C)

Conditions

• Posttraumatic Stress Disorder

Interventions

Type	Name	Description
DRUG	Nepicastat	100-800mg
DRUG	Placebo	100-800mg placebo

Timeline

• Start date: 2009-07-01
• Primary completion: 2012-07-05
• Completion: 2012-08-30
• First posted: 2008-04-16
• Last updated: 2017-10-13
• Results posted: 2017-06-01

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study