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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 wh

Detailed Summary:

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)
  • Significantly higher rates of PTSD response and remission
  • Significantly improved quality of life

Biomarker Hypotheses:

  • The NE (norepinephrine) to DA ratios in nepicastat-treated subjects will be significantly lower at the end of study than at baseline assessment and lower at the end of study than the placebo-treated subjects.
  • Baseline NE to DA ratios and hyper-arousal symptom severity will be correlated.
  • Reduction from baseline in hyper-arousal symptoms and in NE to DA ratios of PTSD patients will be positively correlated. This correlation may be stronger for nepicastat-treated subjects than for the placebo-treated subjects.

Sponsor: Tuscaloosa Research & Education Advancement Corporation

Current Primary Outcome: Primary Outcome is determined by the CAPS scores. [ Time Frame: 3 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome: the secondary outcome measures (DTS, Quality of Life Measures) [ Time Frame: 3 years ]

Original Secondary Outcome: Same as current

Information By: Tuscaloosa Research & Education Advancement Corporation

Dates:
Date Received: March 10, 2008
Date Started: April 2009
Date Completion:
Last Updated: July 2, 2014
Last Verified: July 2014