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NCT Number: NCT00659230

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

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.

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Key information

Conditions

Posttraumatic Stress Disorder Mental Disorders Stress Disorders, Post-Traumatic Stress Disorders, Traumatic Trauma and Stressor Related Disorders

Age range

19 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Tuscaloosa VAMC, Tuscaloosa, Alabama, United States

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About this study

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)

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Signed informed consent
  • Patient understands the risks and benefits and agrees to visit frequency and procedures
  • Male or female
  • Any race or ethnic origin
  • Served in OIF/OEF or Afghanistan conflicts or other Southwest Asia conditions
  • Currently Active Duty, National Guard, Reservist, Veteran, and/or Retired Military
  • Diagnosis of PTSD (by MINI (Mini International Neuropsychiatric Interview) and CAPS-DX (Clinician Administered PTSD scale- Diagnostic Form) using Rule of Fours and total CAPS-DX score of 45)
  • No substance use disorders in the previous 2 weeks and no substance dependence disorders in the past 4 weeks (except for nicotine and caffeine)
  • Free of psychotropic medication for 2 weeks prior to randomization
  • Physical and laboratory panel are within normal limits or not clinically significant
  • Women of childbearing potential must be using medically-approved methods of birth control
  • ≥19 to 65 years of age

Exclusion criteria

  • Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders
  • Actively considering plans of suicide or homicide
  • Psychotic symptoms that in the investigator's opinion impair the patient's ability to give informed consent or make it unsafe for patient to be maintained without a neuroleptic
  • Unstable general medical conditions or a contraindication to the use of nepicastat
  • Women planning to become pregnant or breastfeed during the study
  • Current or pending incarceration
  • Terminal Illness

Treatment and study plan

Nepicastat

Drug

100-800mg

Other names: SYN117, Dopamine beta hydroxylase (DBH) inhibitor

Placebo

Drug

100-800mg placebo

Primary outcomes

  1. Clinician Administered PTSD Scale Subscore D (Hyperarousal)

    Time frame: Baseline, week 2, 4 and 6

    The Clinician Administered PTSD Scale subscore D (CAPS-D) measures the hyperarousal cluster for PTSD symptoms (5 items). Higher scores indicate greater severity. Range for CAPS-D is zero to 40. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

Secondary outcomes

  1. Clinician Administered PTSD Scale Total Score

    Time frame: Baseline, week 2,4, and 6

    The Clinician Administered PTSD Scale (CAPS) measures the full spectrum of PTSD symptoms. Higher scores indicate greater severity. Range for CAPS is zero to 136. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

  2. Clinician Administered PTSD Scale Subscale B Score

    Time frame: 6 weeks

    The Clinician Administered PTSD Subscale B (CAPS-B) measures the re-experiencing cluster of PTSD symptoms. Higher scores indicate greater severity. Range for CAPS-B is zero to 40. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78). Blake, D.D., Weathers, F.W., Nagy, L.M., Kaloupek, D.G., Gusman, F.D., Charney, D.S., Kean, T.M., 1995, The development of a clinician-administered PTSD scale. Journal of Traumatic Stress, 8:75-90.

  3. Clinician Administered PTSD Scale Subscale C Score

    Time frame: Baseline, week 2, 4, and 6

    The Clinician Administered PTSD Subscale C (CAPS-C) measures the Avoidance and emotional numbing cluster of PTSD symptoms. Higher scores indicate greater severity. Range for CAPS-C is zero to 56. The CAPS has acceptable test-retest reliability (0.98), sensitivity (0.84), specificity (0.95), internal consistency (0.76-0.88) and validity (κ=0.78).

Sponsors and collaborators

Lead sponsor

Tuscaloosa Research & Education Advancement Corporation

Other

Collaborators

  • Acorda Therapeutics
  • Baylor College of Medicine
  • James J. Peters Veterans Affairs Medical Center
  • Ralph H. Johnson VA Medical Center
  • San Diego Veterans Healthcare System

Registry information

Official study title

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

Acronym: Nepicastat

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Apr 16, 2008
Registry last updated
Oct 13, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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