Assessing the Impact of dTMS on Neural Targets Associated With Alcohol Use Disorder (NEST-A)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder (AUD); Transcranial Magnetic Stimilation
• Intervention / Treatment: Device: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Active; Device: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Sham

Detailed Description

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
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eileen G Fischer, BS; Phone Number: 210-993-2065; Email: grace.fischer@stanford.edu
• Study Contact Backup: Name: Samantha J Ward, BS; Phone Number: 64975 650-493-5000; Email: samward@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • VA Palo Alto Health Care System
      • Contact: Eileen G Fischer, BS; Phone Number: 210-993-2065; Email: grace.fischer@stanford.edu
      • Principal Investigator: Claudia B Padula, PhD
      • Principal Investigator: Michelle R Madore, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: 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.	Device: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Sham; The study will utilize an identical protocol using the H7 coil to administer a sham condition.
Experimental: 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.	Device: Deep Transcranial Magnetic Stimulation (dTMS) H7 coil - Active; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	1-4 days post-treatment
Change in Resting-State Salience Network Functional Connectivity, Measured via fMRI	Resting-state functional connectivity between the dACC and prefrontal cortex (PFC) will be measured using CONN.	1-4 days post treatment
Relapse Status, assessed by Timeline Followback (TLFB)	Relapse will be defined as any alcohol use following the post-treatment period, assessed using TLFB. Outcome will be reported as a binary (yes/no) variable.	3 months post-treatment
Total Number of Alcoholic Drinks Consumed, Assessed by Timeline Followback (TLFB)	Self-reported alcohol use over the 3-month follow-up period will be assessed via TLFB, and the total number of standard alcoholic drinks consumed will be calculated and reported.	3 months post-treatment

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Claudia B Padula, PhD, Stanford University; Principal Investigator: Michelle R Madore, PhD, Stanford University

Publications and helpful links

General Publications

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

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 21, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Veterans; Neuroimaging; Relapse; Deep Transcranial Magnetic Stimulation (dTMS)
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Pathological Conditions, Signs and Symptoms; Recurrence; Alcoholism
• Other Study ID Numbers: 78836; R01AA031552 (U.S. NIH Grant/Contract: National Institutes of Health); 1R01AA031552-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Any data, specimens, forms, reports, and other records that leave the site will be identified only by a participant ID number to maintain confidentiality. The ID Number will have no relationship to any aspect of identifiable private information. Therefore, the data associated with each participant will be completely de-identified and there will be no mechanism by which users can re-identify participant data (e.g., name, address) with the subject code.
• IPD Sharing Time Frame: Three to twelve months after publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes