Combat DisordersNCT00371176
A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD
A study testing Exposure therapy and D-Cycloserine in people with Combat Disorders and Stress Disorders, Post-Traumatic, run by US Department of Veterans Affairs at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Combat Disorders, Stress Disorders, Post-Traumatic
- What is being tested?
- Exposure therapy and D-Cycloserine
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Jul 2012
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- A lifetime history of:
- bipolar disorder
- schizophrenia
- psychosis
- delusional disorders or obsessive-compulsive disorder
- organic brain syndrome
Show all 18Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Boston Health Care System
Boston, Massachusetts, 02130
About this study
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.
Read the 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.
- Conditions
- Combat Disorders, Stress Disorders, Post-Traumatic
- Being tested
- Exposure therapy, D-Cycloserine, Placebo pill
- Keywords
- Cognitive Behavior Therapy, Cognitive enhancers, Combat Disorders, D-Cycloserine, Stress Disorders, Post-Traumatic
- Medical subject headings
- Combat Disorders, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure therapyBehavioural
A manualized form of treatment that involves vividly visualizing indexed trauma with the guidance of a therapist
D-CycloserineDrug
A partial NMDA agonist that has been shown in human trials to facilitate and strengthen extinction with CBT.
Placebo pillOther
| Study group | Role | What they receive |
|---|---|---|
| D-Cycloserine | Experimental | Brief imaginal exposure therapy plus DCS pill Receives: Behavioral: Exposure therapy; Drug: D-Cycloserine |
| Placebo | Placebo comparator | Brief imaginal exposure therapy plus Placebo pill Receives: Behavioral: Exposure therapy; Other: Placebo pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Pre Intervention
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.
Measured: Post Intervention
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.
Measured: 3 month follow-up
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.
Measured: 6 month follow-up
Secondary outcomes (8)
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.
Measured: Pre Intervention
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.
Measured: Post intervention
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.
Measured: 3 month follow-up
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.
Measured: 6 month follow-up
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.
Measured: Pre intervention
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.
Measured: Post intervention
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.
Measured: 3 month follow-up
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.
Measured: 6 month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2006 (estimated)
- Study startOct 2006
- Primary completionSep 2011
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Combat DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Brett T. Litz, PhD, Principal investigator, VA Boston Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00371176
- Sponsor's protocol ID
- ORD-NIMH-20061
- Status last verified
- Dec 2013
- First submitted
- 31 Aug 2006
- Last updated
- 4 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22694905
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Trial of D-Cycloserine and Exposure Therapy for Combat-PTSD
- ClinicalTrials.gov ID
- NCT00371176
- Acronym / sponsor ID
- ORD-NIMH-20061
- Conditions
- Combat Disorders, Stress Disorders, Post-Traumatic
- Keywords
- Cognitive Behavior Therapy, Cognitive enhancers, Combat Disorders, D-Cycloserine, Stress Disorders, Post-Traumatic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Oct 2006
- Primary completion
- Sep 2011 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 1 Sep 2006 (estimated)
- Results
- Posted 4 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-Cycloserine | Experimental | Behavioral: Exposure therapy, Drug: D-CycloserineBrief imaginal exposure therapy plus DCS pill |
| Placebo | Placebo comparator | Behavioral: Exposure therapy, Other: Placebo pillBrief imaginal exposure therapy plus Placebo pill |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (18 listed)
- bipolar disorder
- schizophrenia
- psychosis
- delusional disorders or obsessive-compulsive disorder
- organic brain syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exposure therapyA manualized form of treatment that involves vividly visualizing indexed trauma with the guidance of a therapist | Behavioural | D-Cycloserine, Placebo |
| D-CycloserineA partial NMDA agonist that has been shown in human trials to facilitate and strengthen extinction with CBT. | Drug | D-Cycloserine |
| Placebo pill | Other | Placebo |
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.
8 secondary outcomes
PTSD Checklist
Time frame: Pre Intervention
PTSD Checklist
Time frame: Post intervention
PTSD Checklist
Time frame: 3 month follow-up
PTSD Checklist
Time frame: 6 month follow-up
Beck Depression Inventory
Time frame: Pre intervention
Beck Depression Inventory
Time frame: Post intervention
Beck Depression Inventory
Time frame: 3 month follow-up
Beck Depression Inventory
Time frame: 6 month follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22694905Litz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brett T. Litz, PhD principal investigator
VA Boston Health Care System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exposure therapy and D-Cycloserine in people with Combat Disorders and Stress Disorders, Post-Traumatic, run by US Department of Veterans Affairs at 1 site 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 2 inclusion and 18 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 4 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2014). 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-IV (time frame: Pre Intervention). The study lists 4 primary outcomes in all. 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 NCT00371176, which also lists 1 linked publication.
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 4 Feb 2014.