A Placebo-Controlled Trail of D-Cycloserine and Exposure Therapy for Combat-PTSD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00371176
First received: August 31, 2006
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

The primary aim of this project is to examine whether administration of D-Cycloserine (DCS), a partial 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.


Condition Intervention
Combat Disorders
Stress Disorders, Post-Traumatic
Behavioral: Exposure therapy
Drug: D-Cycloserine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled Trail of D-Cycloserine and Exposure Therapy for Combat-PTSD

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Clinician Administered PTSD Scale-IV [ Time Frame: Pre and Post Intervention, 3 and 6 month follow ups. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Structured Clinical Interview for DSM-IV; [ Time Frame: Diagnostic session, post-evaluation, 3-month follow-up, and 6-month follow-up ] [ Designated as safety issue: No ]
  • PTSD Checklist [ Time Frame: All time points ] [ Designated as safety issue: No ]
  • Beck Anxiety Inventory [ Time Frame: Pre and Post Intervention and 3 and 6 month follow ups ] [ Designated as safety issue: No ]
  • Revised Beck Depression Inventory [ Time Frame: All time points ] [ Designated as safety issue: No ]
  • Alcohol Use Disorders Identification Test [ Time Frame: Pre-and Post-intervention, 3 and 6-month follow-up ] [ Designated as safety issue: Yes ]
  • Posttraumatic Cognitions Inventory [ Time Frame: Pre-and Post-intervention, 3 and 6-month follow-up ] [ Designated as safety issue: No ]
  • Deployment Risk and Resilience Inventory [ Time Frame: Pre-intervention ] [ Designated as safety issue: No ]
  • Quality of Life Enjoyment and Satisfaction Questionnaire [ Time Frame: Pre-and Post-intervention, 3 and 6-month follow-up ] [ Designated as safety issue: No ]
  • Trauma Related Guilt Inventory [ Time Frame: Diagnostic session, Post-evaluation, 3-month follow-up, and 6-month follow-up ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: October 2006
Study Completion Date: July 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Compares efficacy of DCS relative to placebo for facilitating exposure therapy outcomes.
Behavioral: Exposure therapy
A manualized form of treatment that involves vividly visualizing indexed trauma with the guidance of a therapist
Drug: D-Cycloserine
A partial NMDA agonist that has been shown in human trials to facilitate and strengthen extinction with CBT.

Detailed Description:

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 measures will also be administered at screening, throughout the 6 weeks of treatment, and at 3- and 6- month follow up.

Comparison(s): OEF/OIF veterans with PTSD treated with CBT plus DCS, compared to OEF/OIF veterans with PTSD treated with CBT plus placebo.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female outpatients 18 years of age or older who served in Operation Iraqi Freedom or Operation Enduring Freedom (OIF/OEF) and who have a primary diagnosis (designated by the patient as the most important source of distress of PTSD.
  • Willingness and ability to comply with the requirements of the study protocol.

Exclusion Criteria:

A lifetime history of:

  • bipolar disorder
  • schizophrenia
  • psychosis
  • delusional disorders or obsessive-compulsive disorder
  • organic brain syndrome
  • cognitive dysfunction that could interfere with capacity to engage in therapy
  • a history of substance or alcohol dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation.
  • Patients with significant suicidal ideation or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate services.
  • Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment.
  • Serious medical illness or instability for which hospitalization may be likely within the next year.
  • Patients with a current or past history of seizures
  • Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months).
  • Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration specifically targeting PTSD is excluded. General supportive therapy initiated > 3 months prior is acceptable.
  • Patients with seizures or ongoing severe cognitive impairment that compromised mental status.
  • Patients receiving Isoniazid.
  • Patients unable to understand study procedures and participate in the informed consent process.
  • Patients with a history of renal insufficiency (creatinine clearance less than 50 mL/min).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00371176

Locations
United States, Massachusetts
VA Boston Health Care System
Boston, Massachusetts, United States, 02130
Sponsors and Collaborators
Investigators
Principal Investigator: Brett T. Litz, PhD VA Boston Health Care System
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00371176     History of Changes
Other Study ID Numbers: ORD-NIMH-20061
Study First Received: August 31, 2006
Last Updated: January 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Cognitive Behavior Therapy
Cognitive enhancers
Combat Disorders
D-Cycloserine
Stress Disorders, Post-Traumatic

Additional relevant MeSH terms:
Combat Disorders
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Anxiety Disorders
Mental Disorders
Cycloserine
Nootropic Agents
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 16, 2013