D-cycloserine and Virtual Reality Exposure to Treat Iraq War Veterans With PTSD

Study Overview
=================
Brief Summary
-----------------
This study will determine whether a combination of virtual reality exposure therapy and D-cycloserine will reduce post-traumatic stress disorder symptoms in Iraq war veterans.

Detailed Description
-----------------
Post-traumatic stress disorder (PTSD) is a type of anxiety disorder affecting people who have witnessed or experienced a traumatic event. Veterans of war are at an increased risk for developing PTSD because of their experiences with war and combat. Symptoms of PTSD often include flashbacks or nightmares, depression, anxiety or uneasiness, and feeling emotionally numb or distant toward others. Fortunately, PTSD can be treated, usually with some combination of anti-depressants, anti-anxiety medication, and therapy. Virtual reality exposure (VRE) therapy is a new type of treatment that helps people to overcome anxiety about trauma by facing situations with the use of virtual reality. D-cycloserine is a medication that has been found to enhance the effects of psychotherapy in recent studies. This study will determine the effectiveness of VRE therapy plus D-cycloserine at reducing PTSD symptoms in Iraq war veterans. During this study, all participants will undergo one educational session and five VRE sessions. The first session will involve gathering information, learning common reactions to trauma, and participating in a breathing relaxation approach. The following five sessions will involve reviewing memories of Iraq and watching virtual Iraq sequences. Each participant will wear a head-mounted display during which they will view scenario settings such as cities, humvee convoys, and scenes related to combat. Participants will be randomly assigned to receive D-cycloserine, alprazolam (anti-anxiety drug), or placebo one half-hour before each VRE session. Prior to the first treatment session, participants will undergo a startle reaction procedure. This will entail hearing sudden tones that last a fraction of a second, and viewing virtual reality scenes. Three small electrodes, attached to each participant's face, will measure the number of eye blinks during the procedure. At several times throughout the study, heart rate and skin conductance will also be measured with electrodes. Collection of saliva samples and measurement of blood pressure will also occur several times during this study. Before, during, and immediately after treatment, participants will complete questionnaires. Participants will be contacted 3, 6, and 12 months after treatment to assess symptoms and to schedule a time for an interview, additional questionnaires, and the virtual reality-based assessment.

Official Title
-----------------
A Cognitive Enhancer May Facilitate Behavioral Exposure Therapy for Veterans With PTSD

Conditions
-----------------
Stress Disorder, Post Traumatic

Intervention / Treatment
-----------------
* Drug: D-Cycloserine
* Drug: Alprazolam
* Behavioral: Virtual Reality Exposure Therapy
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meets DSM-IV criteria for PTSD due to Iraq military trauma Speaks English Healthy overall Exclusion Criteria: History of mania, schizophrenia, or other psychoses Suicidal Current alcohol or drug dependence Medication free within 2 weeks of study entry for any medication that has been taken less than daily for the past month and medicine free within 4 weeks of study entry for any anxiolytic medication that has been taken daily for the last month or more Pregnant Special medical conditions, such as kidney insufficiency, chronic diseases, or history of significant head injury Stabilized on potentially data obscuring medication such as glucocorticoids

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Participants will receive VRE therapy and D-cycloserine | Drug: D-Cycloserine<br>* D-Cycloserine doses will be 50 mg. There will be 5 pills total during study, each given 30 minutes prior to each VRE session.<br>Behavioral: Virtual Reality Exposure Therapy<br>* VRE includes viewing scenes of virtual Iraq via a head mounted display. Other stimuli presented include sounds, smells and vibration. Each session will be 60 minutes with approximately 30 to 45 minutes of that wearing head mounted display.<br>|
| Active Comparator: B<br>Participants will receive VRE therapy and alprazolam | Drug: Alprazolam<br>* Alprazolam doses will be 0.25 mg. There will be 5 pills total during study, each given 30 minutes prior to each VRE session.<br>* Other names: Xanax;Behavioral: Virtual Reality Exposure Therapy<br>* VRE includes viewing scenes of virtual Iraq via a head mounted display. Other stimuli presented include sounds, smells and vibration. Each session will be 60 minutes with approximately 30 to 45 minutes of that wearing head mounted display.<br>|
| Placebo Comparator: C<br>Participants will receive VRE therapy and placebo | Behavioral: Virtual Reality Exposure Therapy<br>* VRE includes viewing scenes of virtual Iraq via a head mounted display. Other stimuli presented include sounds, smells and vibration. Each session will be 60 minutes with approximately 30 to 45 minutes of that wearing head mounted display.<br>Drug: Placebo<br>* Placebo will be administered in the same manner as the active drugs.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician-Administered PTSD Scale (CAPS) | Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered. | Baseline | 
| Clinician-Administered PTSD Scale (CAPS) | Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered. | Posttreatment, 8 weeks | 
| Clinician-Administered PTSD Scale (CAPS) | Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered. | Month 3 | 
| Clinician-Administered PTSD Scale (CAPS) | Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered. | Month 6 | 
| Clinician-Administered PTSD Scale (CAPS) | Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTSD Symptom Scale Self-Report | PTSD Symptom Scale - Self-Report Version (PSS-SR) is a 17-item self-reported questionnaire to assess symptoms of PTSD. Each of the 17 items describe PTSD symptoms which respondents rate in terms of their frequency or severity using a Likert-type scale ranging from 0 (not at all or only one time) to 3 (almost always or five or more times per week). Ratings on items are summed to create three subscales, including re-experiencing, avoidance, and arousal, as well as a total score (that ranges from 0 to 51). The total score higher than 13 indicates on likelihood of PTSD. | Baseline | 
| PTSD Symptom Scale Self-Report | PTSD Symptom Scale - Self-Report Version (PSS-SR) is a 17-item self-reported questionnaire to assess symptoms of PTSD. Each of the 17 items describe PTSD symptoms which respondents rate in terms of their frequency or severity using a Likert-type scale ranging from 0 (not at all or only one time) to 3 (almost always or five or more times per week). Ratings on items are summed to create three subscales, including re-experiencing, avoidance, and arousal, as well as a total score (that ranges from 0 to 51). The total score higher than 13 indicates on likelihood of PTSD. | Posttreatment, 8 weeks | 
| PTSD Symptom Scale Self-Report | PTSD Symptom Scale - Self-Report Version (PSS-SR) is a 17-item self-reported questionnaire to assess symptoms of PTSD. Each of the 17 items describe PTSD symptoms which respondents rate in terms of their frequency or severity using a Likert-type scale ranging from 0 (not at all or only one time) to 3 (almost always or five or more times per week). Ratings on items are summed to create three subscales, including re-experiencing, avoidance, and arousal, as well as a total score (that ranges from 0 to 51). The total score higher than 13 indicates on likelihood of PTSD. | Month 3 | 
| PTSD Symptom Scale Self-Report | PTSD Symptom Scale - Self-Report Version (PSS-SR) is a 17-item self-reported questionnaire to assess symptoms of PTSD. Each of the 17 items describe PTSD symptoms which respondents rate in terms of their frequency or severity using a Likert-type scale ranging from 0 (not at all or only one time) to 3 (almost always or five or more times per week). Ratings on items are summed to create three subscales, including re-experiencing, avoidance, and arousal, as well as a total score (that ranges from 0 to 51). The total score higher than 13 indicates on likelihood of PTSD. | Month 6 | 
| PTSD Symptom Scale Self-Report | PTSD Symptom Scale - Self-Report Version (PSS-SR) is a 17-item self-reported questionnaire to assess symptoms of PTSD. Each of the 17 items describe PTSD symptoms which respondents rate in terms of their frequency or severity using a Likert-type scale ranging from 0 (not at all or only one time) to 3 (almost always or five or more times per week). Ratings on items are summed to create three subscales, including re-experiencing, avoidance, and arousal, as well as a total score (that ranges from 0 to 51). The total score higher than 13 indicates on likelihood of PTSD. | Month 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
D-Cycloserine, Virtual Reality, Exposure Therapy, Veterans, Cognitive Behavior Therapy, Translational Research