tDCS Plus Virtual Reality for PTSD (TAVRE)

• ClinicalTrials.gov Identifier: NCT03372460
• Recruitment Status: Recruiting
• First Posted: December 13, 2017
• Last Update Posted: January 27, 2023
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Study Description

Brief Summary:

This study will test the effectiveness 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 will test 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.

Condition or disease	Intervention/treatment	Phase
Post-Traumatic Stress Disorder	Device: Active stimulation; Device: Sham stimulation; Other: Virtual Reality (VR)	Not Applicable

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 has 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. To do this, investigators at the Providence VA Medical Center will use a standardized virtual reality (VR) setting to deliver trauma-related content. The virtual reality setting involves three, 8-minute driving scenarios, 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 tDCS+VR session. Participants will also undergo a MRI before and after completion of all six 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-tDCS+VR session EEG and an optional 1-month follow-up MRI.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants are assigned to receive either active or sham stimulation during the tDCS+VR sessions in parallel for the duration of the study
• Masking: Double (Participant, Investigator)
• Masking Description: double blind tDCS
• Primary Purpose: Treatment
• Official Title: Combined Transcranial Direct Current Stimulation and Virtual Reality for PTSD
• Actual Study Start Date: April 2, 2018
• Estimated Primary Completion Date: August 1, 2023
• Estimated Study Completion Date: August 1, 2023

Arms and Interventions

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).	Device: Active stimulation; For active tDCS, the investigators will use a 1x1 configuration with the anode placed over EEG coordinate AF7 (using the 10-20 EEG convention) and the cathode over Fz. The investigators will use 3x3 cm sponge covered electrodes and a 2mA current for 25 minutes per session.; Other Name: Active tDCS; Other: Virtual Reality (VR); Participants will undergo VR exposure to trauma-related context.
Sham Comparator: Sham Stimulation; Sham tDCS will include a 30-second ramp up to 1mA, 30 seconds of stimulation at 1mA, followed by a 30-second ramp down to off. The device will remain off for the remainder of the session. This process will be used for each of the 6 sessions during a 2 week period.	Device: Sham stimulation; For sham tDCS, the investigators will use the same configuration of active tDCS, with the anode over AF7 and the cathode over Fz. The investigators will use 3x3 cm sponge covered electrodes and 1mA for 30 seconds, with a ramp up/down over 30 seconds per session.; Other Name: Sham tDCS; Other: Virtual Reality (VR); Participants will undergo VR exposure to trauma-related context.

Outcome Measures

Primary Outcome Measures :

1. Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) Total Score [ Time Frame: Average 2.5 weeks ]
   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.
2. Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) [ Time Frame: Average 2.5 weeks ]
   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: 14-70). The raw total score is transformed into a percentage maximum possible score using the following formula: (raw total score minimum score)/(maximum possible raw score minimum score). Higher outcomes indicate better quality of life, greater enjoyment, and satisfaction.
3. Psychophysiology (Skin Conductance Reactivity; SCR) [ Time Frame: Average 2.5 weeks ]
   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 endpoint, to correlate these measures and evaluate changes attributable to active tDCS+VR compared to sham.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Noah S Philip, MD; (401) 273-7100 ext 6200; noah.philip@va.gov

Contact: Mascha Frank, PhD; (401) 273-7100 ext 6256; mascha.frank@va.gov

Locations

United States, Rhode Island

Providence VA Medical Center, Providence, RI; Recruiting

Providence, Rhode Island, United States, 02908-4734

Contact: Sydney K Brigido, BA 401-273-7100 ext 4328 Sydney.Brigido@va.gov

Contact: Noah S Philip, MD (401) 273-7100 ext 6200 noah.philip@va.gov

Principal Investigator: Noah S. Philip, MD

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Noah S. Philip, MD; Providence VA Medical Center, Providence, RI

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT03372460
• Other Study ID Numbers: D2450-R; 2017-053 ( Other Identifier: PVAMC IRB ); 1633742 ( Other Identifier: PVAMC IRB )
• First Posted: December 13, 2017
• Last Update Posted: January 27, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by VA Office of Research and Development:

Transcranial Direct Current Stimulation; Stress Disorders, Post-Traumatic; Virtual Reality; Prefrontal Cortex; Veterans; Quality of Life

Additional relevant MeSH terms:

Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Trauma and Stressor Related Disorders; Mental Disorders