Assessing the Impact of Deep TMS Neuromodulation on Neural Circuits Associated With Alcohol Use Disorder

N/ANot Yet RecruitingNCT06949423

Stanford University100 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

100

Conditions

Alcohol Use Disorder (AUD)Transcranial Magnetic Stimilation

Interventions

Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - ActiveDEVICE

The study will utilize the H7 coil to administer active Deep Transcranial Magnetic Stimulation (dTMS) to the dorsal anterior cingulate cortex (dACC), a core salience network node.

Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - ShamDEVICE

The study will utilize an identical protocol using the H7 coil to administer a sham condition.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18-75. * 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. Exclusion Criteria: * 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

Locations (1)

VA Palo Alto Health Care System

Palo Alto, California, United States

Outcomes

Primary Outcomes

Change in Dorsal Anterior Cingulate Cortex Function (dACC) Activation During the FACES Task, Measured via fMRI

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.

Time frame: 1-4 days post treatment

Percentage of Days Abstinent from Alcohol, Assessed by Timeline Followback (TLFB)

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.

Time frame: 3-months post treatment

Percentage of Heavy Drinking Days, Assessed by Timeline Followback (TLFB)

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.

Time frame: 3 months post-treatment

Secondary Outcomes

Change in Salience Network Functional Connectivity During FACES Task, Measured via fMRI

Functional connectivity between the dACC and prefrontal cortex (PFC) will be assessed using fMRI during the FACES Task. Connectivity strength will be calculated using psychophysiological interaction (PPI) analysis or similar methods.

Time frame: 1-4 days post treatment

Change in Resting-State Salience Network Activation, Measured via fMRI

Resting-state fMRI will assess dACC activation. Measures will include percent signal change pre- to post-treatment.

Time frame: 1-4 days post-treatment

Central Contacts

Samantha J Ward, BS

CONTACT

650-493-5000 samward@stanford.edu

Eileen G Fischer, BS

CONTACT

210-993-2065 grace.fischer@stanford.edu

Data from ClinicalTrials.gov

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