针对同时患有酒精使用障碍和轻度创伤性脑损伤的退伍军人功能残疾的定制神经经颅磁刺激靶点：一项试点随机对照试验方案

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.

作者信息

Herrold Amy A, Aaronson Alexandra L, Bhaumik Dulal, Durazzo Timothy, Livengood Sherri L, Ramic Alma, Riordan Patrick, Jordan Neil, Parrish Todd, Mallinson Trudy, Kale Ibuola O, Billups Andrea, Krese Kelly, Kletzel Sandra, Philip Noah S, Bender Pape Theresa L

机构信息

Edward Hines Jr, VA Hospital, Hines, IL, United States.

Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

出版信息

JMIR Res Protoc. 2025 Jun 23;14:e64909. doi: 10.2196/64909.

DOI:10.2196/64909

PMID:40550124

Abstract

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.

摘要

背景

酒精使用障碍（AUD）和轻度创伤性脑损伤（mTBI）常同时出现，会加重症状并对功能产生负面影响。AUD与mTBI同时存在（AUD + mTBI）代表了一种独特的异质性脑状态，会影响症状和功能。重复经颅磁刺激（rTMS）是一种非侵入性神经调节治疗方法，越来越多的证据表明其可单独改善AUD和mTBI的脑功能及症状。然而，对于单独的每种情况或二者同时出现时，最佳的神经靶点或刺激治疗部位尚无共识。

目的

本研究旨在（1）测试针对定制神经靶点进行高频rTMS治疗AUD + mTBI退伍军人功能残疾的初步疗效，以及（2）评估rTMS对AUD + mTBI退伍军人功能残疾影响的可持续性。

方法

这项单盲随机对照试验（RCT）纳入了从退伍军人事务部医院招募的寻求治疗的AUD + mTBI退伍军人。退伍军人将被随机分配到（1）使用神经导航的新型TMS靶点部位，或（2）使用Beam F3方法刺激标准临床左侧背外侧前额叶皮层。所有参与者首先接受10次每日的假rTMS治疗，随后由经过培训的TMS管理人员进行10次每日的主动rTMS（10 Hz）治疗。退伍军人将在假rTMS和主动rTMS疗程前后以及治疗后2周、1个月、3个月和6个月的随访时间点完成自我报告研究问卷。主要结局是世界卫生组织残疾评估量表2.0。次要结局包括时间追溯日历上的酒精使用情况、宾夕法尼亚酒精渴望量表、强迫性饮酒量表、酒精渴望问卷、神经行为症状量表、DSM - 5创伤后应激障碍检查表、贝克抑郁量表第二版、贝克焦虑量表以及情绪和焦虑症状问卷。

结果

本研究方案已获得爱德华·H·海因斯退伍军人事务部医院机构审查委员会的批准（19 - 021）。本研究包括美国食品药品监督管理局的研究设备豁免（G180292）。制定了一个6年的研究计划时间表，包括因2019冠状病毒病大流行而产生的成本和无成本延期。截至2025年6月，总体而言，27名参与本研究的AUD + mTBI退伍军人已完成神经靶点识别阶段，正在等待随机对照试验阶段的入组。随机对照试验阶段的数据收集即将开始，预计2026年4月完成。我们预计本研究结果将于2027年5月公布。