Clinical Trial: A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD

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

Official Title: A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD

Brief Summary: The primary aim of this project is to examine whether administration of D-Cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist that has been shown to facilitate fear extinction, enhances the therapeutic benefit of exposure-based cognitive behavioral therapy (CBT) in OEF/OIF veterans with PTSD.

Detailed Summary:

War-zone-related posttraumatic stress disorder (PTSD) is a major psychiatric disorder that includes specific disabling symptoms and impairments that interfere with a soldier's ability to do his or her job. There is strong evidence for cognitive behavior therapy (CBT) in treating PTSD in civilians, which suggests a prescription for returning veterans, but approximately 40% of patients retain a PTSD diagnosis (e.g., Foa et al., 1999) and drop-out rates are ~25%. It is imperative to develop novel evidence-based early interventions that are more acceptable to recent veterans and less draining of treatment resources. If CBT can be shortened and its efficacy boosted by cognitive enhancers then it is more likely that soldiers will get the most efficacious treatments for acute stress and PTSD. Our aim is to develop a program that is brief and effective, but will have long-term benefits for veterans by virtue of its greater amenability to self-management and treatment adherence beyond the therapy context.

This study is a randomized, controlled, double-blind treatment trial comparing CBT plus DCS to CBT plus placebo. Participants will be 68 OEF/OIF veterans with PTSD randomly assigned to CBT plus DCS or CBT plus placebo. Procedures to screen subjects prior to randomization include a detailed phone screen, administration and collection of questionnaires, a medical assessment, and two baseline structured clinical interviews. Following randomization, both groups will receive the identical 6 session exposure-based CBT protocol. The DCS-augmented group will receive 50 mg of DCS 30 minutes prior to the four CBT sessions involving imaginal exposure, whereas the placebo-augmented group will receive a placebo pill prior to these sessions. Assessment interviews conducted by independent evaluators will occur at pre-treatment, post-treatment, and at 3, and 6-month follow-up. Self-report measur
Sponsor: VA Office of Research and Development

Current Primary Outcome:

• Clinician Administered PTSD Scale-IV [ Time Frame: Pre Intervention ]
  A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
• Clinician Administered PTSD Scale-IV [ Time Frame: Post Intervention ]
  A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
• Clinician Administered PTSD Scale-IV [ Time Frame: 3 month follow-up ]
  A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
• Clinician Administered PTSD Scale-IV [ Time Frame: 6 month follow-up ]
  A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.

Original Primary Outcome:

• Clinician Administered PTSD Scale-IV; Pre- and Post intervention, 3 and 6-month follow-up
• Structured Clinical Interview for DSM-IV; Pre- and Post-intervention, 3 and 6-month follow-up

Current Secondary Outcome:

• PTSD Checklist [ Time Frame: Pre Intervention ]
  A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
• PTSD Checklist [ Time Frame: Post intervention ]
  A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
• PTSD Checklist [ Time Frame: 3 month follow-up ]
  A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
• PTSD Checklist [ Time Frame: 6 month follow-up ]
  A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
• Beck Depression Inventory [ Time Frame: Pre intervention ]
  A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
• Beck Depression Inventory [ Time Frame: Post intervention ]
  A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
• Beck Depression Inventory [ Time Frame: 3 month follow-up ]
  A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
• Beck Depression Inventory [ Time Frame: 6 month follow-up ]
  A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.

Original Secondary Outcome:

• PTSD Checklist; Pre- and Post-intervention, Weeks 1-6, 3 and 6-month follow-up
• Beck Anxiety Inventory; Pre- and Post-intervention, 3 and 6-month follow-up
• Revised Beck Depression Inventory; Pre- and Post-intervention, Weeks 1-6, 3 and 6-month follow-up
• Alcohol Use Disorders Identification Test; Pre-and Post-intervention, 3 and 6-month follow-up
• Posttraumatic Cognitions Inventory; Pre-and Post-intervention, 3 and 6-month follow-up
• Deployment Risk and Resilience Inventory; Pre-intervention
• Quality of Life Enjoyment and Satisfaction Questionnaire; Pre-and Post-intervention, 3 and 6-month follow-up
• Credibility/Expectancy Questionnaire; Week 4
• Homework Compliance; Weeks 2-6

Information By: VA Office of Research and Development

Dates:
Date Received: August 31, 2006
Date Started: October 2006
Date Completion:
Last Updated: December 16, 2013
Last Verified: December 2013