Post Traumatic Stress DisorderPhase 3NCT01352637

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

A Phase 3 study testing DCS (D-Cycloserine ) + Prolonged Imaginal Exposure and DCS (D-Cycloserine ) + Virtual Reality Exposure in people with Post Traumatic Stress Disorder, run by Weill Medical College of Cornell University at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Post Traumatic Stress Disorder
What is being tested?: DCS (D-Cycloserine ) + Prolonged Imaginal Exposure and DCS (D-Cycloserine ) + Virtual Reality Exposure
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 192 participants
Where: 5 sitesUnited States
Study dates: May 2011to Sep 2018
Phase: Phase 3
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 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Emory University
Atlanta, Georgia
Walter Reed Army Medical Center/National Intrepid Center of Excellence (NICoE)
Bethesda, Maryland
VA Long Beach Healthcare System
Long Beach, California
University of Southern California
Los Angeles, California
Weill Cornell Medical College
New York, New York

Other trials in United States

About this study

Official title: Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure With a Cognitive Enhancer

Read the 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.

Conditions: Post Traumatic Stress Disorder
Being tested: DCS (D-Cycloserine ) + Prolonged Imaginal Exposure, DCS (D-Cycloserine ) + Virtual Reality Exposure, Placebo + Prolonged Imaginal Exposure, Placebo (sugar pill) + Virtual Reality Exposure
Keywords: Traumatic Event, Trauma Survivor, Exposure Therapy, PTSD DCS, Virtual Reality Exposure, Veteran, Combat-related PTSD
Medical subject headings: Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DCS (D-Cycloserine ) + Prolonged Imaginal ExposureDrug
50mg DCS (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure
DCS (D-Cycloserine ) + Virtual Reality ExposureDrug
50mg DCS (taken once a week on the day of the therapy session) + Virtual Reality Exposure
Placebo + Prolonged Imaginal ExposureDrug
Placebo (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure
Placebo (sugar pill) + Virtual Reality ExposureDrug
Placebo (taken once a week on the day of the therapy session) + Virtual Reality Exposure

Study groups in NCT01352637
Study group	Role	What they receive
Placebo + Prolonged Imaginal Exposure	Placebo comparator	Drug: Placebo (sugar pill) + Prolonged Imaginal Exposure (PE) PTSD treatment Receives: Drug: Placebo + Prolonged Imaginal Exposure
Placebo + VR exposure	Placebo comparator	Drug: Placebo (sugar pill) + Virtual Reality Exposure (VR) PTSD treatment Receives: Drug: Placebo (sugar pill) + Virtual Reality Exposure
DCS + Prolonged Imaginal Exposure	Active comparator	Drug: 50mg DCS (D-Cycloserine ) + Prolonged Imaginal Exposure (PE) PTSD treatment Receives: Drug: DCS (D-Cycloserine ) + Prolonged Imaginal Exposure
DCS+VR exposure	Active comparator	Drug: 50mg DCS (D-Cycloserine ) + Virtual Reality Exposure (VR) PTSD treatment Receives: Drug: DCS (D-Cycloserine ) + Virtual Reality Exposure

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: after weekly treatment session 9 (at posttreatment assessment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2011Sep 2018

First posted12 May 2011 (estimated)
Study startMay 2011
Primary completionSep 2018
Study completionSep 2018

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 (2)Papers the sponsor has linked to this study.
Other trials for Post Traumatic Stress DisorderStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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.
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 192 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01352637
Sponsor's protocol ID: 1005011047
Status last verified: Jun 2019
First submitted: 18 Feb 2011
Last updated: 2 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 35896533
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.
PubMed 31669451

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 2 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure With a Cognitive Enhancer
ClinicalTrials.gov ID: NCT01352637
Acronym / sponsor ID: 1005011047
Conditions: Post Traumatic Stress Disorder
Keywords: Traumatic Event, Trauma Survivor, Exposure Therapy, PTSD DCS, Virtual Reality Exposure, Veteran, Combat-related PTSD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 192 participants (actual)
Lead sponsor: Weill Medical College of Cornell UniversityUniversity, hospital or other
Collaborators: United States Department of Defense, Emory University, University of Southern California, VA Long Beach Healthcare System, National Intrepid Center of Excellence
Study start: May 2011 (actual)
Primary completion: Sep 2018 (actual)
Study completion: Sep 2018 (actual)
First posted: 12 May 2011 (estimated)
Results: Posted 2 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4
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.

Arm	Type	Receives
Placebo + Prolonged Imaginal Exposure	Placebo comparator	Drug: Placebo + Prolonged Imaginal ExposureDrug: Placebo (sugar pill) + Prolonged Imaginal Exposure (PE) PTSD treatment
Placebo + VR exposure	Placebo comparator	Drug: Placebo (sugar pill) + Virtual Reality ExposureDrug: Placebo (sugar pill) + Virtual Reality Exposure (VR) PTSD treatment
DCS + Prolonged Imaginal Exposure	Active comparator	Drug: DCS (D-Cycloserine ) + Prolonged Imaginal ExposureDrug: 50mg DCS (D-Cycloserine ) + Prolonged Imaginal Exposure (PE) PTSD treatment
DCS+VR exposure	Active comparator	Drug: DCS (D-Cycloserine ) + Virtual Reality ExposureDrug: 50mg DCS (D-Cycloserine ) + Virtual Reality Exposure (VR) PTSD treatment

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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;

Key exclusion criteria (8 listed)

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;

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
DCS (D-Cycloserine ) + Prolonged Imaginal Exposure50mg DCS (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure	Drug	DCS + Prolonged Imaginal Exposure
DCS (D-Cycloserine ) + Virtual Reality Exposure50mg DCS (taken once a week on the day of the therapy session) + Virtual Reality Exposure	Drug	DCS+VR exposure
Placebo + Prolonged Imaginal ExposurePlacebo (taken once a week on the day of the therapy session) + Prolonged Imaginal Exposure	Drug	Placebo + Prolonged Imaginal Exposure
Placebo (sugar pill) + Virtual Reality ExposurePlacebo (taken once a week on the day of the therapy session) + Virtual Reality Exposure	Drug	Placebo + VR exposure

Primary outcome

CAPS-IV at the End of Treatment
Time frame: after weekly treatment session 9 (at posttreatment assessment)
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.

Results and safety

Results posted to the registry on 2 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Virtual Reality Exposure (VRE)	97	70
Prolonged Imaginal Exposure (PE)	95	62
Drug: D-Cycloserine (DCS)	0	0
Drug: Placebo	0	0

Primary outcome: CAPS-IV at the End of Treatment

Time frame: after weekly treatment session 9 (at posttreatment assessment). Mean (Standard Deviation). Unit: units on a scale

Measure	Virtual Reality Exposure (VRE) n = 97	Prolonged Imaginal Exposure (PE) n = 95	Drug: D-Cycloserine (DCS) n = 95	Drug: Placebo n = 97
Value	52.42 (26.55)	50.61 (25.22)	54.20 (26.72)	48.59 (24.71)

Population analysed: Total sample size is n=192. Randomization allocation ratio was 1:1:1:1 to VRE vs. PE and DCS vs. placebo. Study had 2 co-primary aims to examine: 1. the effects of DCS (n=95) vs placebo (n=97) augmentation of exposure therapy 2. the relative efficacy of VRE (n=97) and PE (n=95) on PTSD symptoms.

Adverse events

Time frame: During treatment (9 weekly therapy sessions).. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Virtual Reality Exposure (VRE)	0 of 97 (0%)	0 of 97 (0%)	0 of 97
Prolonged Imaginal Exposure (PE)	3 of 95 (3.2%)	0 of 95 (0%)	0 of 95
Drug: D-Cycloserine (DCS)	0 of 95 (0%)	0 of 95 (0%)	0 of 95
Drug: Placebo	1 of 97 (1%)	0 of 97 (0%)	0 of 97

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35896533Difede 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.
Derived from this study: PubMed 31669451Difede 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.
Related InfoLink provided by the sponsor.

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.

JoAnn Difede, Ph.D. principal investigator

Weill Medical College of Cornell University

Barbara Rothbaum, Ph.D., ABPP principal investigator

Emory University

Skip Rizzo, Ph. D. principal investigator

University of Southern California

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 6 inclusion and 8 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 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2019). 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?

CAPS-IV at the End of Treatment (time frame: after weekly treatment session 9 (at posttreatment assessment)). 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 NCT01352637, which also lists 2 linked publications.

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 2 Jul 2019.

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

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Publications

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (6 listed)

Key exclusion criteria (8 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: CAPS-IV at the End of Treatment

Adverse events

Research links

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Improving Student Mental Health Through a Universal Trauma-Informed Intervention

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Assessing of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies

Trauma-Related Attributions in Trauma Treatment: An Observational Study

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Referral and contact

Questions about this trial

Log in to keep searching

Participant flow

Primary outcome: CAPS-IV at the End of Treatment

Adverse events