A Customized Neural Transcranial Magnetic Stimulation Target for Functional Disability Among Veterans With Co-Occurring Alcohol Use Disorder and Mild Traumatic Brain Injury: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND

Alcohol use disorder (AUD) and mild traumatic brain injury (mTBI) commonly co-occur, exacerbating symptoms and negatively impacting function. Co-occurring AUD and mTBI (AUD+mTBI) represents a unique and heterogeneous brain state impacting symptoms and function. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory treatment with burgeoning evidence for improving brain function and symptoms for AUD and mTBI each alone. However, there is no consensus on the optimal neural target or treatment site of stimulation for either condition alone or when they co-occur.

OBJECTIVE

This study aims to (1) test the preliminary efficacy of high-frequency rTMS provided to a customized neural target to treat functional disability among veterans with AUD+mTBI and (2) assess the sustainability of rTMS effects on functional disability among veterans with AUD+mTBI.

METHODS

This single-blind randomized controlled trial (RCT) involved treatment-seeking veterans with AUD+mTBI recruited from a Department of Veterans Affairs hospital. Veterans will be randomly assigned to (1) a novel TMS target site using neuronavigation or (2) standard clinical left dorsolateral prefrontal cortex using the Beam F3 method. All participants first receive 10 daily sessions of sham rTMS, followed by 10 daily sessions of active rTMS (10 Hz) provided by a trained TMS administrator. Veterans will complete self-report study questionnaires before and after sham and active rTMS session blocks as well as at 2-week, 1-month, 3-month, and 6-month posttreatment follow-up time points. The primary outcome is the WHO Disability Assessment Schedule 2.0. The secondary outcomes include alcohol use on the Timeline Follow-Back calendar, the Penn Alcohol Craving Scale, the Obsessive-Compulsive Drinking Scale, the Alcohol Craving Questionnaire, the Neurobehavioral Symptom Inventory, the PTSD Checklist for DSM-5, the Beck Depression Inventory-II, the Beck Anxiety Inventory, and the Mood and Anxiety Symptom Questionnaire.

RESULTS

This study protocol was approved by the institutional review board of the Edward Hines Jr Department of Veterans Affairs Hospital (19-021). This study includes a Food and Drug Administration investigational device exemption (G180292). A 6-year research plan timeline was developed, including cost and no-cost extensions due to the COVID-19 pandemic. As of June 2025, overall, 27 veterans with AUD+mTBI who had been enrolled in the study had completed the neural target identification phase and were awaiting enrollment in the RCT phase. Data collection for the RCT phase will be initiated soon and is expected to be completed by April 2026. We expect the results of this study to be available by May 2027.

CONCLUSIONS

We will be able to provide preliminary evidence of the efficacy, safety, and feasibility of a novel TMS target for veterans with AUD+mTBI.

TRIAL REGISTRATION

ClinicalTrials.gov NCT04043442; https://www.clinicaltrials.gov/study/NCT04043442.