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

NCT06949423 | Not Yet Recruiting FDA Device

• 2 other identifiers: 78836R01AA031552
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol Use Disorder (AUD); Transcranial Magnetic Stimilation

Keywords

Veterans; Deep Transcranial Magnetic Stimulation (dTMS); Neuroimaging; Relapse

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  3 months post-treatment

Secondary Outcomes (5)

• 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

Study Arms (2)

Active dTMS

EXPERIMENTAL

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.

Device: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Active

Sham dTMS

SHAM COMPARATOR

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.

Device: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Sham

Interventions

Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Active DEVICE

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.

Active dTMS

Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Sham DEVICE

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

Sham dTMS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

VA Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

Related Publications (5)

• Padula CB, Tenekedjieva LT, McCalley DM, Al-Dasouqi H, Hanlon CA, Williams LM, Kozel FA, Knutson B, Durazzo TC, Yesavage JA, Madore MR. Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Front Psychiatry. 2022 May 17;13:893833. doi: 10.3389/fpsyt.2022.893833. eCollection 2022.

  PMID: 35656355 BACKGROUND

• Padula CB, Tenekedjieva LT, McCalley DM, Morales JM, Madore MR. Accelerated deep TMS in alcohol use disorder: A preliminary pilot trial targeting the dorsal anterior cingulate cortex increases neural target engagement and abstinence. Brain Stimul. 2024 Sep-Oct;17(5):1098-1100. doi: 10.1016/j.brs.2024.09.002. Epub 2024 Sep 13. No abstract available.

  PMID: 39265786 BACKGROUND

• Harel M, Perini I, Kampe R, Alyagon U, Shalev H, Besser I, Sommer WH, Heilig M, Zangen A. Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices. Biol Psychiatry. 2022 Jun 15;91(12):1061-1069. doi: 10.1016/j.biopsych.2021.11.020. Epub 2021 Dec 6.

  PMID: 35067356 BACKGROUND

• Peters SK, Dunlop K, Downar J. Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment. Front Syst Neurosci. 2016 Dec 27;10:104. doi: 10.3389/fnsys.2016.00104. eCollection 2016.

  PMID: 28082874 BACKGROUND

• Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010 Jan;35(1):217-38. doi: 10.1038/npp.2009.110.

  PMID: 19710631 BACKGROUND

MeSH Terms

Conditions

Alcoholism; Recurrence

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Claudia B Padula, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Michelle R Madore, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha J Ward, BS

CONTACT

650-493-5000; samward@stanford.edu

Eileen G Fischer, BS

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 2-arm, 1:1 ratio, randomized, double-blind, sham-controlled

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 29, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Three to twelve months after publication.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

US (1)