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

Primary Purpose

Combat Disorders, Stress Disorders, Post-Traumatic

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exposure therapy
D-Cycloserine
Placebo pill
Sponsored by
US Department of Veterans Affairs
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Combat Disorders focused on measuring Cognitive Behavior Therapy, Cognitive enhancers, Combat Disorders, D-Cycloserine, Stress Disorders, Post-Traumatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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., intra uterine device, 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).

Sites / Locations

  • VA Boston Health Care System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

D-Cycloserine

Placebo

Arm Description

Brief imaginal exposure therapy plus DCS pill

Brief imaginal exposure therapy plus Placebo pill

Outcomes

Primary Outcome Measures

Clinician Administered PTSD Scale-IV
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
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
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
A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.

Secondary Outcome Measures

PTSD Checklist
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
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
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
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
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
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
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
A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.

Full Information

First Posted
August 31, 2006
Last Updated
December 16, 2013
Sponsor
US Department of Veterans Affairs
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1. Study Identification

Unique Protocol Identification Number
NCT00371176
Brief Title
A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD
Official Title
A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
US Department of Veterans Affairs

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Combat Disorders, Stress Disorders, Post-Traumatic
Keywords
Cognitive Behavior Therapy, Cognitive enhancers, Combat Disorders, D-Cycloserine, Stress Disorders, Post-Traumatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
D-Cycloserine
Arm Type
Experimental
Arm Description
Brief imaginal exposure therapy plus DCS pill
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Brief imaginal exposure therapy plus Placebo pill
Intervention Type
Behavioral
Intervention Name(s)
Exposure therapy
Intervention Description
A manualized form of treatment that involves vividly visualizing indexed trauma with the guidance of a therapist
Intervention Type
Drug
Intervention Name(s)
D-Cycloserine
Intervention Description
A partial NMDA agonist that has been shown in human trials to facilitate and strengthen extinction with CBT.
Intervention Type
Other
Intervention Name(s)
Placebo pill
Primary Outcome Measure Information:
Title
Clinician Administered PTSD Scale-IV
Description
A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
Time Frame
Pre Intervention
Title
Clinician Administered PTSD Scale-IV
Description
A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
Time Frame
Post Intervention
Title
Clinician Administered PTSD Scale-IV
Description
A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
Time Frame
3 month follow-up
Title
Clinician Administered PTSD Scale-IV
Description
A 17-item, semi-structured interview of PTSD symptoms. The range of scores is 0-136, with a higher value representing a worse outcome.
Time Frame
6 month follow-up
Secondary Outcome Measure Information:
Title
PTSD Checklist
Description
A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
Time Frame
Pre Intervention
Title
PTSD Checklist
Description
A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
Time Frame
Post intervention
Title
PTSD Checklist
Description
A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
Time Frame
3 month follow-up
Title
PTSD Checklist
Description
A 17-item, self-report measure of PTSD symptoms. The range of scores is 17-85, with a higher value representing a worse outcome.
Time Frame
6 month follow-up
Title
Beck Depression Inventory
Description
A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
Time Frame
Pre intervention
Title
Beck Depression Inventory
Description
A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
Time Frame
Post intervention
Title
Beck Depression Inventory
Description
A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
Time Frame
3 month follow-up
Title
Beck Depression Inventory
Description
A 21-item, self-report measure of depression symptoms. The range of scores is 0-63, with a higher value representing a worse outcome.
Time Frame
6 month follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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., intra uterine device, 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brett T. Litz, PhD
Organizational Affiliation
VA Boston Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Boston Health Care System
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02130
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22694905
Citation
Litz BT, Salters-Pedneault K, Steenkamp MM, Hermos JA, Bryant RA, Otto MW, Hofmann SG. A randomized placebo-controlled trial of D-cycloserine and exposure therapy for posttraumatic stress disorder. J Psychiatr Res. 2012 Sep;46(9):1184-90. doi: 10.1016/j.jpsychires.2012.05.006. Epub 2012 Jun 12.
Results Reference
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A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD

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