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

Tracking Information
First Submitted Date ICMJE	July 24, 2006
First Posted Date ICMJE	July 25, 2006
Results First Submitted Date	November 7, 2014
Results First Posted Date	November 19, 2014
Last Update Posted Date	January 8, 2016
Study Start Date ICMJE	September 2006
Actual Primary Completion Date	June 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 17, 2014)	Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Baseline ]Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered.; Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Posttreatment, 8 weeks ]Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered.; Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Month 3 ]Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered.; Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Month 6 ]Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered.; Clinician-Administered PTSD Scale (CAPS) [ Time Frame: Month 12 ]Scores may range from 0 (no symptoms) to 136 (severe symptoms). The score is based on the first 17 CAPS items administered.
Original Primary Outcome Measures ICMJE; (submitted: July 24, 2006)	psychophysiological measures Pre-and Post-tx;3,6,12 month FU; Clinician Administered PTSD Scale Pre-and Post-tx;3,6,12 month FU; PTSD Symptom Scale Self-Report Pre-and Post-tx;3,6,12 month FU; Cognitive Global Impressions each session; post-tx, 3,6,12 month FU; Quality of Life Inventory Pre-and Post-tx;3,6,12 month FU; State-Trait Anxiety Inventory Pre-and Post-tx;3,6,12 month FU; Beck Depression Inventory Pre-and Post-tx;3,6,12 month FU
Change History	Complete list of historical versions of study NCT00356278 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 17, 2014)	PTSD Symptom Scale Self-Report [ Time Frame: Baseline ]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.; PTSD Symptom Scale Self-Report [ Time Frame: Posttreatment, 8 weeks ]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.; PTSD Symptom Scale Self-Report [ Time Frame: Month 3 ]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.; PTSD Symptom Scale Self-Report [ Time Frame: Month 6 ]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.; PTSD Symptom Scale Self-Report [ Time Frame: Month 12 ]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.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	D-cycloserine and Virtual Reality Exposure to Treat Iraq War Veterans With PTSD
Official Title ICMJE	A Cognitive Enhancer May Facilitate Behavioral Exposure Therapy for Veterans With PTSD
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.
Study Type ICMJE	Interventional
Study Phase	Phase 2; Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Stress Disorder, Post Traumatic
Intervention ICMJE	Drug: D-Cycloserine D-Cycloserine doses will be 50 mg. There will be 5 pills total during study, each given 30 minutes prior to each VRE session.; Drug: Alprazolam Alprazolam doses will be 0.25 mg. There will be 5 pills total during study, each given 30 minutes prior to each VRE session. Other Name: Xanax; Behavioral: Virtual Reality Exposure Therapy 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.; Drug: Placebo Placebo will be administered in the same manner as the active drugs.
Study Arms	Experimental: A Participants will receive VRE therapy and D-cycloserine Interventions: Drug: D-Cycloserine Behavioral: Virtual Reality Exposure Therapy; Active Comparator: B Participants will receive VRE therapy and alprazolam Interventions: Drug: Alprazolam Behavioral: Virtual Reality Exposure Therapy; Placebo Comparator: C Participants will receive VRE therapy and placebo Interventions: Behavioral: Virtual Reality Exposure Therapy Drug: Placebo
Publications *	Norrholm SD, Jovanovic T, Gerardi M, Breazeale KG, Price M, Davis M, Duncan E, Ressler KJ, Bradley B, Rizzo A, Tuerk PW, Rothbaum BO. Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy. Behav Res Ther. 2016 Jul;82:28-37. doi: 10.1016/j.brat.2016.05.002. Epub 2016 May 7.; Rothbaum BO, Price M, Jovanovic T, Norrholm SD, Gerardi M, Dunlop B, Davis M, Bradley B, Duncan EJ, Rizzo A, Ressler KJ. A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans. Am J Psychiatry. 2014 Jun;171(6):640-8. doi: 10.1176/appi.ajp.2014.13121625.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 11, 2013)	156
Original Enrollment ICMJE; (submitted: July 24, 2006)	150
Actual Study Completion Date	June 2014
Actual Primary Completion Date	June 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	21 Years to 65 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00356278
Other Study ID Numbers ICMJE	IRB00024846; DATR AD-TS ( Other Identifier: Other ); R01MH070880 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Barbara O. Rothbaum, PhD, Emory University
Study Sponsor ICMJE	Emory University
Collaborators ICMJE	National Institute of Mental Health (NIMH)
Investigators ICMJE	Principal Investigator: Barbara O. Rothbaum, PhD, ABPP Emory University
PRS Account	Emory University
Verification Date	January 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP