Accessing the Impact of Deep TMS Neuromodulation on Neural Circuits Associated With Alcohol Use Disorder
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change in Dorsal Anterior Cingulate Cortex Function (dACC) Activation During the FACES Task, Measured via fMRI
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of deep transcranial magnetic stimulation as a treatment for Veterans with Alcohol Use Disorder (AUD) to decrease the exceedingly high rate of relapse associated with this condition.
详细描述
Alcohol use disorder (AUD) is a highly prevalent disorder with a chronic relapse-remit cycle, and over 60% of individuals relapse within months of treatment. Preclinical and human research over the last several decades have defined AUD as a neural circuit-based disorder, which are driven by changes in salience network (SN) function. Emerging non-invasive neuromodulation techniques, such as deep transcranial magnetic stimulation (dTMS), can directly modify neural targets that are related to AUD relapse risk, including the SN.
Preclinical and clinical studies have shown that manipulation of deep cortical nodes within the salience network (SN), such as the dorsal anterior cingulate cortex (dACC), can reduce compulsive drinking. Our lab has demonstrated that blunted dACC activation to affective cues predicts relapse - identifying dACC as a promising neuromodulation target. A systematic interrogation of salience network neuromodulation bridges preclinical and clinical research and has the potential to revolutionize AUD treatment. Our preliminary data demonstrates 1) feasibility of the proposed dTMS protocol and 2) promising neural and clinical outcomes. Specifically, those who received this innovative intervention demonstrated increased dACC activation to affective cues from pre- to post-treatment, dynamic changes in functional connectivity and 100% abstinence at follow up.
Building on these data and a theory-driven conceptual framework, the current proposal aims to systematically address three remaining scientific gaps: 1) to what extent does dTMS stimulation of the dACC modify drinking rates and neural targets, 2) can target engagement be a marker of early treatment response, and 3) how long do the effects of dTMS last? This research is significant and innovative as it utilizes a novel, neuromodulation technique to directly manipulate neural networks that drive relapse in AUD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomization will be completed and stored with staff in the Biostatistic Core. Treatment assignments will be recorded on a USB drive read by the device in order to ensure treaters and study investigators remain blinded. In the instance that a serious adverse event (SAE) occur, consultation with the Data Safety and Monitoring Board and the Institutional Review Board will occur to determine the appropriateness of breaking the blind. The blind may be broken for a specific individual in order to determine whether the SAE is related to the treatment.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Current DSM-5 diagnosis of moderate to severe AUD (≥4 diagnostic symptoms).
- •Ability to obtain a Motor Threshold (MT) will be determined during the screening process.
- •Has an adequately stable condition and environment to enable attendance at scheduled clinic visits.
- •Able to read, understand and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments.
- •If on a medication regimen for comorbid symptoms, that regimen will be stable for the duration of the study and patient will be willing to remain on this regimen during the treatment phase.
- •Fluency in English.
排除标准
- •Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) contraindications: such as a cardiac pacemaker, cochlear implant, or an implanted device (deep brain stimulation, metal in the head, metal in the body, claustrophobia, pregnant or breastfeeding or other ferromagnetic device/objected in the head and body within 30 cm of the treatment coil.
- •General medical condition, disease or neurological disorder that interferes with the assessments or participation.
- •Unable to safely withdraw, at least two weeks prior to treatment, from medications that increase seizure risk.
- •Current substance abuse (except caffeine or nicotine) as determined by positive toxicology screen.
- •Have a mass lesion, cerebral infarct, or other active CNS disease, including an alcohol-related seizure or a seizure disorder.
- •A recent suicide attempt (defined as within the last 30 days) or presence of current suicidal plan or intent. Patients at risk for suicide will be required to establish a written safety plan involving their primary therapist before entering the study.
- •Severe impediment to vision, hearing and/or hand movement, likely to interfere with the ability to follow study protocols.
- •Greater than mild traumatic brain injury (defined as greater than 10 minutes loss of consciousness).
- •Taking benzodiazepine or neuroleptic medications, or any medication known to alter seizure threshold
- •Acute or unstable chronic illness.
- •Current or lifetime history of bipolar disorder or psychosis
研究组 & 干预措施
Active dTMS
Participants will receive 30 sessions of active-dTMS to the dACC/mPFC with the H7 coil, administered 3 times per day over 10 consecutive business days. Each treatment visit will last approximately 30 minutes in total.
干预措施: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Active (Device)
Sham dTMS
Participants will receive 30 sham dTMS sessions, administered 3 times per day over 10 consecutive business days. Each treatment visit will last approximately 30 minutes in total.
干预措施: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Sham (Device)
结局指标
主要结局
Change in Dorsal Anterior Cingulate Cortex Function (dACC) Activation During the FACES Task, Measured via fMRI
时间窗: 1-4 days post treatment
dACC activation to threat faces will be measured using fMRI during the FACES task, designed to assess emotional processing. Activation will be quantified as percent signal change from baseline (pre-treatment) to post-treatment scan.
Percentage of Days Abstinent from Alcohol, Assessed by Timeline Followback (TLFB)
时间窗: 3-months post treatment
Alcohol abstinence will be assessed using the TLFB structured interview method. The outcome will be calculated as the percentage of alcohol-free days out of the total number of days in the 3-month follow-up period post-treatment.
Percentage of Heavy Drinking Days, Assessed by Timeline Followback (TLFB)
时间窗: 3 months post-treatment
Heavy drinking days are defined as ≥5 drinks/day for men and ≥4 drinks/day for women within a 2-hour period. Self-reported data via TLFB used to calculate the percentage of heavy drinking days during the 3-month follow-up treatment.
次要结局
- Change in Salience Network Functional Connectivity During FACES Task, Measured via fMRI(1-4 days post treatment)
- Change in Resting-State Salience Network Activation, Measured via fMRI(1-4 days post-treatment)
- Change in Resting-State Salience Network Functional Connectivity, Measured via fMRI(1-4 days post treatment)
- Relapse Status, assessed by Timeline Followback (TLFB)(3 months post-treatment)
- Total Number of Alcoholic Drinks Consumed, Assessed by Timeline Followback (TLFB)(3 months post-treatment)
研究者
Claudia Padula
Assistant Professor
Stanford University