Clinical trial NCT03372460: tDCS Plus Virtual Reality for PTSD
Official title: Combined Transcranial Direct Current Stimulation and Virtual Reality for PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post-Traumatic Stress Disorder
Keywords: Transcranial Direct Current Stimulation
Stress Disorders, Post-Traumatic
Virtual Reality
Prefrontal Cortex
Veterans
Quality of Life
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2017-12-13
Enrollment: 65
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: Participants are assigned to receive either active or sham stimulation during the tDCS+VR sessions in parallel for the duration of the study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) Total Score
timeFrame: Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up
measure: Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ)
timeFrame: Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up
measure: Psychophysiology (Skin Conductance Reactivity; SCR)
timeFrame: Measured during each tDCS+VR session, each session up to 1 hour
Secondary outcomes:
measure: Inventory of Depressive Symptomatology Self-Report (IDSSR)
timeFrame: Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up
measure: Social and Occupational Function Scale (SOFAS)
timeFrame: Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up
measure: Clinician Administered PTSD Scale for the DSM-5 (CAPS-5)
timeFrame: Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up
Other outcomes:
Locations:
city: Providence
country: United States
facility: Providence VA Medical Center, Providence, RI
state: Rhode Island
Study officials:
affiliation: Providence VA Medical Center, Providence, RI
name: Noah S. Philip, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.