Clinical trial NCT01352637: Enhancing Exposure Therapy for Post Traumatic Stress Disorder (PTSD): Virtual Reality and Imaginal Exposure With a Cognitive Enhancer
Official title: Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure With a Cognitive Enhancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Traumatic Stress Disorder
Keywords: Traumatic Event
Trauma Survivor
Exposure Therapy
PTSD DCS
Virtual Reality Exposure
Veteran
Combat-related PTSD
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Emory University
name: University of Southern California
name: VA Long Beach Healthcare System
name: National Intrepid Center of Excellence
First posted: 2011-05-12
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The two primary co-aims of this study are

1. to examine the effects of DCS versus placebo (PLA) augmentation of exposure therapy on PTSD symptoms and
2. to examine the relative efficacy of virtual reality enhanced exposure therapy (VRE) and exposure therapy (PE) on PTSD symptoms.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the differences between four active treatment conditions for combat-related Post Traumatic Stress Disorder (PTSD): virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both with DCS or placebo, as well as to examine predictors for PTSD and response to treatment in active duty military personnel, veterans, and civilians who served in Iraq and Afghanistan.

Detailed description: Post Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop following exposure to traumatic events and includes symptoms of re-experiencing the trauma, such as through nightmares and flashbacks, avoidance and numbing, and physical hyperarousal. PTSD has been estimated to affect 10-20% of returning Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) veterans. The most effective intervention found for PTSD is exposure therapy, which can be delivered in different formats, e. g. via virtual reality (VR) and as imaginal exposure. The goal of this study is to test the difference between 4 study conditions: virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both combined with an antibiotic drug, DCS (active pill vs. placebo). D-Cycloserine (DCS), a drug that has been FDA approved for over 20 years, has been hypothesized to enhance the therapeutic effects of exposure therapy.). A secondary purpose of this study is to examine predictors for PTSD and response to PTSD intervention in active duty military personnel, veterans, and civilians who served in Iraq/Afghanistan. Psychophysiological factors (e.g. heart rate, blood pressure) and/or a genetic polymorphism (BDNF Val66Met) obtained from a saliva sample will be examined.

The two primary co-aims are

1. to examine the effects of DCS versus placebo (PLA) augmentation of exposure therapy on PTSD symptoms, and
2. to examine the relative efficacy of virtual reality enhanced exposure therapy (VRE) and exposure therapy (PE) on PTSD symptoms.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of OEF-OIF (Operations Enduring Freedom or Iraqi Freedom) Combat Related PTSD;
2. Female participants of childbearing potential must agree to use an effective method of birth control (i.e., oral contraceptive, Norplant, diaphragm, condom, or spermicide) during the course of the study, or to remain abstinent from sex, to ensure they do not become pregnant during the course of the study;
3. Ability to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments;
4. Participants must be literate in English;
5. Patients must be medically healthy and willing to take the study drug;
6. VRE stimuli available must be consistent with subject's trauma.

Exclusion Criteria:

1. Lifetime or current diagnosis of schizophrenia or other psychotic disorder, bipolar disorder;
2. Participation in a clinical trial during the previous 3 months;
3. Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, CNS tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment;
4. Patients who in the investigator's judgment pose a current suicidal or homicidal risk;
5. Alcohol, medication, or illegal substance dependence within the past 90 days;
6. Treatment with any other concomitant medication with primarily CNS activity, or treatment with any medication that the PI judges not acceptable for this study;
7. history of seizures;
8. Pregnancy or lactation.

Primary outcomes:
measure: CAPS-IV at the End of Treatment
timeFrame: after weekly treatment session 9 (at posttreatment assessment)
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Bethesda
country: United States
facility: Walter Reed Army Medical Center/National Intrepid Center of Excellence (NICoE)
state: Maryland
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: JoAnn Difede, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Barbara Rothbaum, Ph.D., ABPP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Skip Rizzo, Ph. D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Difede J, Rothbaum BO, Rizzo AA, Wyka K, Spielman L, Reist C, Roy MJ, Jovanovic T, Norrholm SD, Cukor J, Olden M, Glatt CE, Lee FS. Enhancing exposure therapy for posttraumatic stress disorder (PTSD): a randomized clinical trial of virtual reality and imaginal exposure with a cognitive enhancer. Transl Psychiatry. 2022 Jul 27;12(1):299. doi: 10.1038/s41398-022-02066-x.
citation: Difede J, Rothbaum BO, Rizzo AA, Wyka K, Spielman L, Jovanovic T, Reist C, Roy MJ, Norrholm SD, Glatt C, Lee F. Enhanced exposure therapy for combat-related Posttraumatic Stress Disorder (PTSD): Study protocol for a randomized controlled trial. Contemp Clin Trials. 2019 Dec;87:105857. doi: 10.1016/j.cct.2019.105857. Epub 2019 Oct 24.