tDCS Plus Virtual Reality for PTSD (TAVRE)

Combined Transcranial Direct Current Stimulation and Virtual Reality for PTSD

This study tests the efficacy of combining non-invasive brain stimulation, called transcranial direct current stimulation (tDCS), with virtual reality exposure as a treatment for Veterans with chronic posttraumatic stress disorder (PTSD). Investigators tested whether this intervention improves PTSD symptoms and improves quality of life. Results from this study may be used to develop a new non-medication approach to treating chronic PTSD.

Study Overview

• Status: Completed
• Conditions: Post-Traumatic Stress Disorder
• Intervention / Treatment: Other: Virtual Reality (VR); Device: Active stimulation; Device: Sham stimulation

Detailed Description

PTSD is highly prevalent in Veterans and is associated with significant psychiatric and medical comorbidity, as well as poor quality of life. Despite its prevalence and impact, the success of currently available treatments is mixed, highlighting the need for novel approaches that aim to reduce symptoms and improve outcomes. Prior research demonstrated that reduced activity in a part of the brain, the ventromedial prefrontal cortex (VMPFC), is associated with an inability to regulate fear responses, preventing the generation of safety memories and allowing PTSD symptoms to persist. Targeting the VMPFC with non-invasive electrical brain stimulation may therefore alleviate these symptoms.

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation that may enhance the likelihood of neuronal activity in the VMPFC. In doing so, tDCS prepares the brain to respond to external stimuli and to facilitate learning and memory. Because therapeutic success from exposure to trauma-related content - as used in exposure-based therapy for PTSD - is thought to be based on an adaptive learning process, applying tDCS in combination with exposure to trauma cues may effectively boost exposure-based learning. In this study, investigators at the VA Providence Healthcare System will use a standardized virtual reality (VR) setting to deliver trauma-related content. The virtual reality setting involves three, 8-minute driving scenarios, constituting one VR session, which consist of VR stimuli (sights, sounds, smells, etc.) often encountered in combat training and in theater.

Eligible participants will be randomized to receive six sessions of either active tDCS plus virtual reality (tDCS+VR) or sham tDCS+VR. Clinical and self-report assessments will be completed at baseline, midpoint, and endpoint, as well as 1 and 3 months following the final VR session. Primary outcome measures occur at the 1 month timepoint. Psychophysiology (skin conductance reactivity) will be collected throughout each VR session to capture habituation. Participants will also undergo a MRI before and after completion of all six active or sham tDCS+VR sessions to assess change over time. Additionally, MRI data will be used for electrical field modeling to predict treatment response based on individually obtained electrical field values in PTSD relevant neural circuitry. Participants may also choose to participate in an optional pre-active or sham tDCS+VR session EEG and an optional 1-month follow-up MRI.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02908-4734
      • Providence VA Medical Center, Providence, RI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be a Veteran
• Located in the greater Providence and Boston areas
• Have a diagnosis of chronic PTSD, meeting DSM-5 criteria
• If in treatment, symptomatic despite ongoing stable treatment regimens for at least 6 weeks prior to study procedures.
• Willing and able to comply with all study related procedures and visits
• Capable of independently reading and understanding study materials and providing informed consent.

Exclusion Criteria:

Contraindications to MRI or tDCS, including:

• Implanted device (e.g., deep brain stimulation) or metal in the brain, cervical spinal cord, or upper thoracic spinal cord.
• Skin lesions at the site of stimulation that may increase conductance (e.g., vascular moles or angiomas)
• Pregnancy/lactation, or planning to become pregnant during the study
• Lifetime history of moderate or severe traumatic brain injury (TBI)
• Current unstable medical conditions
• Current (or past if appropriate) significant neurological disorder, or lifetime history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d) cerebral aneurysm.

Other exclusions:

• Primary psychotic disorder
• Bipolar I disorder
• Active moderate/severe substance use disorders (within the last month, excluding nicotine/caffeine)
• Active suicidal intent or plan as detected on screening instruments or in the investigative team's judgment is likely to attempt suicide within 6 months
• Other conditions or circumstances that, in the opinion of the investigator team, have the potential to prevent completion and/or have a confounding effect on outcome assessments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Stimulation; Active stimulation (tDCS) will be used in the dose of 2mA /25 min per day, for 6 sessions over the course of 2 weeks (3 sessions per week).	Other: Virtual Reality (VR); Participants will undergo VR exposure to trauma-related context.; Device: Active stimulation; For active tDCS, the investigators will use a 1x1 configuration with the anode placed over EEG coordinates AF7/Fp1/AF3 (using the 10-20 EEG convention) and the cathode between EEG coordinate OZ and the contralateral mastoid (covering approximately PO8/P8). The investigators will use 3x3 cm sponge covered electrodes and a 2mA current for 25 minutes per session.; Other Names: Active tDCS
Sham Comparator: Sham Stimulation; Sham tDCS uses the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). This process will be used for each of the 6 sessions during a 2 week period.	Other: Virtual Reality (VR); Participants will undergo VR exposure to trauma-related context.; Device: Sham stimulation; For sham tDCS, the investigators will use the same electrode and sponge configuration as active tDCS, but using the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current).; Other Names: Sham tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) Total Score	The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Items are rated on how much the symptom bothered the respondent in the past month (0 = "not at all bothered by" to 4 = "extremely bothered "). A total symptom severity score (range: 0-80) can be obtained by summing the scores for each of the 20 items, with higher scores indicating more severe PTSD symptoms. PCL-5 scores at 1 month was the primary symptom outcome measure for this study.	Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up
Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)	The 16-item QLESQ (short form) evaluates quality of life and other areas of change related to functioning outside of symptom domains (e.g., physical health, mood, leisure time activities, social relationships, etc.). Items are rated on how satisfied the respondent has been in the past week (1 = "very poor" to 5 = "very good "). A total raw score (range: 16-80). Higher outcomes indicate better quality of life, greater enjoyment, and satisfaction.	Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up
Psychophysiology (Skin Conductance Reactivity; SCR)	Psychophysiology will include skin conductance reactivity to specific trauma context virtual reality (VR) cues presented in the VR scenario. SCR to VR events will be measured by the phasic responses that occur after the presentation of discreet VR events. SCR will be compared from baseline to end of tDCS+VR, to correlate these measures and evaluate changes attributable to active tDCS+VR compared to sham.	Measured during each tDCS+VR session, each session up to 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inventory of Depressive Symptomatology Self-Report (IDSSR)	The 28-item IDSSR is a self-report measure of depressive symptom severity. Each item is rated on a scale of 0 to 3 by the participant for a total minimum score of 0 and a maximum score of 84. A higher score on the IDSSR indicates increased depressive symptom severity.	Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up
Social and Occupational Function Scale (SOFAS)	The SOFAS is a scale that focuses on the individual's level of social and occupational functioning and is not directly influenced by the overall severity of the individual's psychological symptoms. Any impairment in social and occupational functioning that is due to general medical conditions is considered in making the SOFAS rating. The SOFAS is usually used to rate functioning for the current period (i.e., the level of functioning at the time of the evaluation). Scores range from 0 to 100, with higher scores indicating better social and occupational functioning.	Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up
Clinician Administered PTSD Scale for the DSM-5 (CAPS-5)	The CAPS-5 is the gold standard in clinician-assessed PTSD symptoms. The CAPS-5 is a 30-item structured interview that can be used to make current (past month) diagnosis of PTSD, make lifetime diagnosis of PTSD, and assess PTSD symptoms over the past week. In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). An interviewee's total severity score on the CAPS-5 represents the sum of the individual severity scores (0-4) for each of the 20 PTSD symptoms; total scores range from 0-80, with higher scores indicating more severe PTSD symptoms.	Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Noah S. Philip, MD, Providence VA Medical Center, Providence, RI

Publications and helpful links

General Publications

• van 't Wout-Frank M, Arulpragasam AR, Faucher C, Aiken E, Shea MT, Jones RN, Greenberg BD, Philip NS. Virtual Reality and Transcranial Direct Current Stimulation for Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2024 May 1;81(5):437-446. doi: 10.1001/jamapsychiatry.2023.5661.

Helpful Links

• Virtual Reality and Transcranial Direct Current Stimulation for Posttraumatic Stress Disorder

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2018
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Quality of Life; Transcranial Direct Current Stimulation; Veterans; Virtual Reality; Stress Disorders, Post-Traumatic; Prefrontal Cortex
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: D2450-R; 2017-053 (Other Identifier: PVAMC IRB); 1633742 (Other Identifier: PVAMC IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No