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Posttraumatic Stress DisorderPhase 2NepicastatNCT00659230

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

A Phase 2 study testing Nepicastat in people with Posttraumatic Stress Disorder, run by Tuscaloosa Research & Education Advancement Corporation at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 19 years and olderHealthy volunteers can take part
Conditions the study is for
Posttraumatic Stress Disorder
What is being tested?
Nepicastat
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
100 participants
Where
3 sitesUnited States
Study dates
1 Jul 2009to 30 Aug 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • VA San Diego Healthcare System

    San Diego, California, 92161

  • James J.Peters VA Medical Center

    The Bronx, New York, 10468

  • Tuscaloosa VAMC

    Tuscaloosa, Alabama, 35404

Other trials in United States

About this study

Official title: 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.

Read the 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)
Being tested
Nepicastat, Placebo
Keywords
PTSD, Veterans, Nepicastat, OIF/OEF
Medical subject headings
Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NepicastatDrug

    Also called SYN117, Dopamine beta hydroxylase (DBH) inhibitor

    100-800mg

  • PlaceboDrug

    100-800mg placebo

Study groups in NCT00659230
Study groupRoleWhat they receive
PlaceboPlacebo comparatorArm 1
Receives: Drug: Placebo
NepicastatActive comparatorArm 2
Receives: Drug: Nepicastat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinician Administered PTSD Scale Subscore D (Hyperarousal)

    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).

    Measured: Baseline, week 2, 4 and 6

Secondary outcomes (3)

  1. Clinician Administered PTSD Scale Total Score

    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).

    Measured: Baseline, week 2,4, and 6

  2. Clinician Administered PTSD Scale Subscale B Score

    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.

    Measured: 6 weeks

  3. Clinician Administered PTSD Scale Subscale C Score

    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).

    Measured: Baseline, week 2, 4, and 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2008 (estimated)
  2. Study start1 Jul 2009
  3. Primary completion5 Jul 2012
  4. Study completion30 Aug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00659230
Sponsor's protocol ID
08-06
Other IDs
PT074384/W81XWH-08-2-0071, PT074384/W81XWH-09-1-0287
Acronym
Nepicastat
Status last verified
Sep 2017
First submitted
10 Mar 2008
Last updated
13 Oct 2017
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kosten TR, Krystal J. Biological mechanisms in posttraumatic stress disorder. Relevance for substance abuse. Recent Dev Alcohol. 1988;6:49-68. doi: 10.1007/978-1-4615-7718-8_3.

    PubMed 3283864

  • Graham DP, Nielsen DA, Kosten TR, Davis LL, Hamner MB, Makotkine I, Yehuda R. Examining the utility of using genotype and functional biology in a clinical pharmacology trial: pilot testing dopamine beta-hydroxylase, norepinephrine, and post-traumatic stress disorder. Psychiatr Genet. 2014 Aug;24(4):181-2. doi: 10.1097/YPG.0000000000000039. No abstract available.

    PubMed 24983834

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nepicastat in people with Posttraumatic Stress Disorder, run by Tuscaloosa Research & Education Advancement Corporation at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinician Administered PTSD Scale Subscore D (Hyperarousal) (time frame: Baseline, week 2, 4 and 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00659230, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2017.

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