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

September 12, 2017 updated by: Lori Davis, MD, Tuscaloosa Research & Education Advancement Corporation

A Randomized, Placebo-Controlled Trial of the Dopamine-B-Hydroxylase (DBH) Inhibitor, Nepicastat, for the Treatment of 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Tuscaloosa, Alabama, United States, 35404
        • Tuscaloosa VAMC
    • California
      • San Diego, California, United States, 92161
        • VA San Diego Healthcare System
    • New York
      • The Bronx, New York, United States, 10468
        • James J.Peters VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Arm 1
Drug: Placebo
100-800mg placebo
Active Comparator: Nepicastat
Arm 2
Drug: Nepicastat
100-800mg
Other Names:
  • SYN117
  • Dopamine beta hydroxylase (DBH) inhibitor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
Baseline, week 2, 4 and 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
Baseline, week 2,4, and 6
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.
6 weeks
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).
Baseline, week 2, 4, and 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tuscaloosa Research & Education Advancement Corporation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Baylor College of Medicine
James J. Peters Veterans Affairs Medical Center
Acorda Therapeutics
San Diego Veterans Healthcare System
Ralph H. Johnson VA Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Carlos Berry, M.D., IRB Tuscaloosa VAMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 5, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 15, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 13, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 12, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 08-06
  • PT074384/W81XWH-08-2-0071 (Other Grant/Funding Number: Department of Defense/USAMRAA)
  • PT074384/W81XWH-09-1-0287 (Other Grant/Funding Number: Department of Defense/USAMRAA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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