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Enhancing Exposure Therapy for Post Traumatic Stress Disorder (PTSD): Virtual Reality and Imaginal Exposure With a Cognitive Enhancer

Primary Purpose

Post Traumatic Stress Disorder

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
DCS (D-Cycloserine ) + Prolonged Imaginal Exposure
DCS (D-Cycloserine ) + Virtual Reality Exposure
Placebo + Prolonged Imaginal Exposure
Placebo (sugar pill) + Virtual Reality Exposure
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post Traumatic Stress Disorder focused on measuring Traumatic Event, Trauma Survivor, Exposure Therapy, PTSD DCS, Virtual Reality Exposure, Veteran, Combat-related PTSD

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • VA Long Beach Healthcare System
  • University of Southern California
  • Emory University
  • Walter Reed Army Medical Center/National Intrepid Center of Excellence (NICoE)
  • Weill Cornell Medical College

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo + Prolonged Imaginal Exposure

Placebo + VR exposure

DCS + Prolonged Imaginal Exposure

DCS+VR exposure

Arm Description

Drug: Placebo (sugar pill) + Prolonged Imaginal Exposure (PE) PTSD treatment

Drug: Placebo (sugar pill) + Virtual Reality Exposure (VR) PTSD treatment

Drug: 50mg DCS (D-Cycloserine ) + Prolonged Imaginal Exposure (PE) PTSD treatment

Drug: 50mg DCS (D-Cycloserine ) + Virtual Reality Exposure (VR) PTSD treatment

Outcomes

Primary Outcome Measures

CAPS-IV at the End of Treatment
Clinician Administered PTSD Scale (CAPS) for the DSM-IV [34]. The CAPS-IV is a structured clinical interview designed to assess the 17 DSM-IV PTSD symptoms. CAPS-IV provides categorical ratings of diagnostic status as well as a quantitative index of symptom severity. The CAPS total severity score is based on response to the 17 items that assess the frequency and intensity of current PTSD symptoms. Symptom severity is assessed separately for past month and past week time frames. CAPS-IV range is 0-136, higher scores mean a worse outcome.

Secondary Outcome Measures

Full Information

First Posted
February 18, 2011
Last Updated
June 13, 2019
Sponsor
Weill Medical College of Cornell University
Collaborators
United States Department of Defense, Emory University, University of Southern California, VA Long Beach Healthcare System, National Intrepid Center of Excellence
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1. Study Identification

Unique Protocol Identification Number
NCT01352637
Brief Title
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

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
May 2011 (Actual)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
September 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
United States Department of Defense, Emory University, University of Southern California, VA Long Beach Healthcare System, National Intrepid Center of Excellence

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Traumatic Stress Disorder
Keywords
Traumatic Event, Trauma Survivor, Exposure Therapy, PTSD DCS, Virtual Reality Exposure, Veteran, Combat-related PTSD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The two primary co-aims of this study are to examine the effects of DCS versus placebo (PLA) augmentation of exposure therapy on PTSD symptoms and to examine the relative efficacy of virtual reality enhanced exposure therapy (VRE) and exposure therapy (PE) on PTSD symptoms.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
192 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo + Prolonged Imaginal Exposure
Arm Type
Placebo Comparator
Arm Description
Drug: Placebo (sugar pill) + Prolonged Imaginal Exposure (PE) PTSD treatment
Arm Title
Placebo + VR exposure
Arm Type
Placebo Comparator
Arm Description
Drug: Placebo (sugar pill) + Virtual Reality Exposure (VR) PTSD treatment
Arm Title
DCS + Prolonged Imaginal Exposure
Arm Type
Active Comparator
Arm Description
Drug: 50mg DCS (D-Cycloserine ) + Prolonged Imaginal Exposure (PE) PTSD treatment
Arm Title
DCS+VR exposure
Arm Type
Active Comparator
Arm Description
Drug: 50mg DCS (D-Cycloserine ) + Virtual Reality Exposure (VR) PTSD treatment
Intervention Type
Drug
Intervention Name(s)
DCS (D-Cycloserine ) + Prolonged Imaginal Exposure
Intervention Description
50mg DCS (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure
Intervention Type
Drug
Intervention Name(s)
DCS (D-Cycloserine ) + Virtual Reality Exposure
Intervention Description
50mg DCS (taken once a week on the day of the therapy session) + Virtual Reality Exposure
Intervention Type
Drug
Intervention Name(s)
Placebo + Prolonged Imaginal Exposure
Intervention Description
Placebo (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure
Intervention Type
Drug
Intervention Name(s)
Placebo (sugar pill) + Virtual Reality Exposure
Intervention Description
Placebo (taken once a week on the day of the therapy session) + Virtual Reality Exposure
Primary Outcome Measure Information:
Title
CAPS-IV at the End of Treatment
Description
Clinician Administered PTSD Scale (CAPS) for the DSM-IV [34]. The CAPS-IV is a structured clinical interview designed to assess the 17 DSM-IV PTSD symptoms. CAPS-IV provides categorical ratings of diagnostic status as well as a quantitative index of symptom severity. The CAPS total severity score is based on response to the 17 items that assess the frequency and intensity of current PTSD symptoms. Symptom severity is assessed separately for past month and past week time frames. CAPS-IV range is 0-136, higher scores mean a worse outcome.
Time Frame
after weekly treatment session 9 (at posttreatment assessment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of OEF-OIF (Operations Enduring Freedom or Iraqi Freedom) Combat Related PTSD; 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; Ability to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments; Participants must be literate in English; Patients must be medically healthy and willing to take the study drug; VRE stimuli available must be consistent with subject's trauma. Exclusion Criteria: Lifetime or current diagnosis of schizophrenia or other psychotic disorder, bipolar disorder; Participation in a clinical trial during the previous 3 months; 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; Patients who in the investigator's judgment pose a current suicidal or homicidal risk; Alcohol, medication, or illegal substance dependence within the past 90 days; Treatment with any other concomitant medication with primarily CNS activity, or treatment with any medication that the PI judges not acceptable for this study; history of seizures; Pregnancy or lactation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
JoAnn Difede, Ph.D.
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Barbara Rothbaum, Ph.D., ABPP
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Skip Rizzo, Ph. D.
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Long Beach Healthcare System
City
Long Beach
State/Province
California
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Walter Reed Army Medical Center/National Intrepid Center of Excellence (NICoE)
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35896533
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.
Results Reference
derived
PubMed Identifier
31669451
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.
Results Reference
derived
Links:
URL
http://www.patss.com
Description
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Enhancing Exposure Therapy for Post Traumatic Stress Disorder (PTSD): Virtual Reality and Imaginal Exposure With a Cognitive Enhancer

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