MPFC Theta Burst Stimulation as a Treatment Tool for Alcohol Use Disorder: Effects on Drinking and Incentive Salience

NCT04998916 | Recruiting DMC FDA Device

• 2 other identifiers: 001027092P50AA010761-26
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to develop transcranial magnetic stimulation (TMS), specifically TMS at a frequency known as theta burst stimulation (TBS), to see how it affects the brain and changes the brain's response to alcohol-related pictures. TMS and TBS are stimulation techniques that use magnetic pulses to temporarily excite specific brain areas in awake people (without the need for surgery, anesthetic, or other invasive procedures). TBS, which is a form of TMS, will be applied over the medial prefrontal cortex, (MPFC), which has been shown to be involved with drinking patterns and alcohol consumption. This study will test whether TBS can be used as an alternative tool to reduce the desire to use alcohol and reducing the brain's response to alcohol-related pictures.

Conditions

Alcohol Use Disorder; Alcohol Drinking; Substance Use; Drinking, Alcohol; Alcohol Use Disorder (AUD)

Keywords

Transcranial Magnetic Stimulation; Medial Prefrontal Cortex; Brain Stimulation; Non-invasive; Adult

Outcome Measures

Primary Outcomes (3)

• Change in Percent Heavy Drinking Days (PHDD) from baseline

  The primary outcome analysis will examine the TMS treatment effect (active vs. sham) on drinking outcomes-measured as percent heavy drinking days (PHDD) (heavy drinking day defined as 4 or more drinks for women and 5 or more drinks for men)-in the follow-up period beginning after the final treatment session. Collected via timeline follow back (TLFB) in three 28-day (month) intervals, this will be analyzed using multivariate mixture models to consider the effect of time (month after treatment) and the interaction of treatment with time, baseline drinking, number of treatment sessions received, and any other potential covariates (e.g., age, nicotine use, time since last drink). Drinking data will be collected on all randomized participants, irrespective of treatment completion. Lower percentages indicate fewer heavy drinking days in the 28-day interval.

  Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)

• Change in Percent Days Abstinent (PDA) from baseline

  The primary outcome analysis will examine the TMS treatment effect (active vs. sham) on drinking outcomes-measured as percent days abstinent (PDA) - in the follow-up period beginning after the final treatment session. Collected via timeline follow back (TLFB) in three 28-day (month) intervals, this will be analyzed using multivariate mixture models to consider the effect of time (month after treatment) and the interaction of treatment with time, baseline drinking, number of treatment sessions received, and any other potential covariates (e.g., age, nicotine use, time since last drink). Drinking data will be collected on all randomized participants, irrespective of treatment completion. Higher percentages indicate increased days abstinent from alcohol in the 28-day interval.

  Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)

• Change in alcohol cue task MRI activation 1-week post treatment from baseline

  For the alcohol cue reactivity task, multivariate mixture model analyses will be used to calculate the difference in activation between the ALC and BEV blocks for vmPFC and ventral striatal ROIs, and to analyze maximum likelihood estimates for ALC vs. BEV activation as a function of time, treatment, and the cross-level interactions of these factors. Specifically, the cue task stimuli will be nested within time (post- vs. pre-treatment scan); time will be nested within participant; and participants will be nested within treatment (Sham vs. Active).

  Baseline (Week 1), Post-treatment (4-weeks from baseline)

Secondary Outcomes (6)

• Change in anxiety via State-Trait Anxiety Inventory from baseline

  Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)

• Change in alcohol use via Obsessive-Compulsive Drinking Scale from baseline

  Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)

• Change in depression via Becks Depression Inventory-II from baseline

  Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)

• Change in alcohol use via Alcohol Audit from baseline

  Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)

• Changes in cognitive performance from baseline

  Baseline (Week 1), Post-treatment (4-weeks from baseline)

Study Arms (2)

Real TBS to the mPFC

EXPERIMENTAL

For continuous theta burst stimulation (cTBS), participants will receive 3 sessions of stimulation per visit over the left medial prefrontal cortex (mPFC) (each train: 3 pulse bursts presented at 5Hz, 15 pulses/sec, 600 pulses/session, 60 sec intertrain interval; 120% RMT, MagPro; 10-15 min inter session interval) using a figure 8 coil (Coil Cool-B65 A/P).

Device: Real TBS to the mPFC

Sham TBS to the mPFC

SHAM COMPARATOR

The MagVenture MagPro system has an integrated, active sham which passes current through two surface electrodes placed on the scalp. The electrodes will be placed on the left frontalis muscle for all sessions. A patient identification card will randomize participants to receive either real or sham stimulation. This system maintains blinding by a gyroscope in the coil which indicates to the clinical staff whether the coil should be rotated up or down for this participant once the card is entered into the machine. One side of the coil is active, the other is sham. The integrity of the double-blind procedure will be assessed by asking the patients and study personnel rate their confidence regarding whether they thought they received real or sham (scale 1-10).

Device: Sham TBS to the mPFC

Interventions

Real TBS to the mPFC DEVICE

This will be delivered with the Magventure Magpro system; 600 pulses of continuous theta burst stimulation with the active sham coil (double blinded using the integrated active sham system).

Real TBS to the mPFC

Sham TBS to the mPFC DEVICE

This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded using the integrated active sham system). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the scalp. The electrodes are placed on the left frontalis muscle under the coil for both the real and sham stimulation sessions.

Sham TBS to the mPFC

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65 (to maximize participation; note: Scalp-to-Cortex distance will be included as a covariate to calculate adjusted TMS dose given expected cortical atrophy in heavy alcohol users and older adults and the demonstrated effect50 on TMS-fMRI responses in addiction)
• Alcohol Use Disorder, determined by DSM-V criteria, using the Structured Clinical Interview for DSM-V
• Consumption of more than 14 drinks (women) or 21 drinks (men) per week, with at least 4 heavy drinking days (defined as ≥ 4 drinks for women and ≥ 5 for men) per week during the 30-days prior to enrolling.
• Able to read and understand questionnaires and informed consent.

You may not qualify if:

• Has metal placed above the neck
• Is at elevated risk of seizure (i.e., has a history of seizures, is currently prescribed medications known to lower seizure threshold)
• Has a history of moderate to severe alcohol withdrawal or medicated alcohol withdrawal
• Has a history of claustrophobia
• Has a history of chronic migraines
• Has a history of traumatic brain injury, including a head injury that resulted in hospitalization, loss of consciousness for more than 10 minutes, or having ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage
• Has an unstable medical illness requiring planned medical/surgical intervention (e.g. chemotherapy, surgical procedure)
• Medications: Is currently taking or initiates a new prescription for drugs known to improve alcohol drinking treatment outcomes (e.g. naltrexone, acamprosate, topiramate) or taking psychiatric/sleeping medications except for stable (1 month) antidepressants/SSRI's. \[Note: this criterion is for scientific rather than safety or patient comfort reasons\].
• Has a history of substance use disorder (other than nicotine) by DSM-V criteria in the past 6 months
• Has current suicidal ideation or homicidal ideation
• Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29401, United States

RECRUITING

MeSH Terms

Conditions

Alcoholism; Alcohol Drinking; Substance-Related Disorders

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Drinking Behavior; Behavior

Central Study Contacts

Lisa M McTeague

CONTACT

842-792-8274; mcteague@musc.edu

Rhia Walton

CONTACT

842-792-8274; waltonrh@musc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: This study will utilize a double-blind, sham-controlled clinical trial to evaluate the efficacy of the TBS treatment to the vmPFC
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 10, 2021
• Study Start: July 6, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)