| City: |
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Tuscaloosa |
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State:
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AL |
| Zip Code: |
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35404 |
| Conditions: |
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Posttraumatic Stress Disorder |
| Purpose: |
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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 (includes Gulf War, Afghanistan, Iraq, Iran, Saudi Arabia, Kuwait or
any military service,combat or otherwise 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 (i.e.
disulfiram), our study in 120 outpatient veterans (as described above) with PTSD will
compare nepicastat 120 mg/day vs. placebo (1:1 monotherapy) in a 6-week double-blind,
randomized clinical trial (RCT). The veterans will be followed for an additional 8 weeks
after the RCT (weeks 7-14), 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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| Study summary: |
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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. |
| Criteria: |
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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 |
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| Study is available at: |
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Tuscaloosa VAMC
Tuscaloosa, AL 35404
United States
Primary Contact:
Sandra Creel
Email: sandra.creel@va.gov
Phone: 205-554-2000
Secondary Contact:
Lori L Davis, M.D.
Email: lori.davis@va.gov
Phone: 205-554-2000 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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