## Protocol Section
### Identification Module
**NCT ID:** NCT06415721

**Brief Title:** Developing Functional Connectivity-Guided TMS for Alcohol Use Disorder

**Official Title:** Developing Functional Connectivity-Guided TMS for Alcohol Use Disorder

#### Organization Study ID Info
**ID:** PADNEW_0003
#### Organization
**Class:** FED
**Full Name:** VA Palo Alto Health Care System
### Status Module
#### Completion Date
**Date:** 2026-01-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-01-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Stanford University

**Class:** NIH

**Name:** National Institute on Alcohol Abuse and Alcoholism (NIAAA)

#### Lead Sponsor

**Class:** FED

**Name:** VA Palo Alto Health Care System

#### Responsible Party

**Investigator Affiliation:** VA Palo Alto Health Care System

**Investigator Full Name:** Daniel McCalley

**Investigator Title:** Postdoctoral Fellow

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** True

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Alcohol Use Disorders are currently positioned as the third leading cause of preventable death in the United States, constituting a humanitarian crisis with substantial financial burden on society and medical facilities. While several pharmacological interventions exist, 60% of individuals who seek these treatments relapse to alcohol within 6 months. These high relapse rates are due in part to elevated brain response to alcohol cues in the environment. This study seeks to evaluate the efficacy of one session of functional Magnetic Resonance Imaging (fMRI) guided transcranial magnetic stimulation (TMS) as a strategy to reduce brain reactivity to alcohol cues.

**Detailed Description:** At least 60% of those with AUD will experience a major relapse period within 6 months of treatment, irrespective of the intervention (psychosocial and/or pharmacological) employed. Consequently, the high prevalence of AUD and relapse following treatment in Veterans is associated with substantial resource allocation and costs for the VA Health Care System. Current pharmacological and psychosocial interventions demonstrate only a moderate level of efficacy, which is reflected in the high rate of relapse in AUD. Transcanial Magnetic Stimulation (TMS) is a neurostimulation method that is at the forefront of innovative, non-invasive, and safe treatments for AUD, and other psychiatric disorders. To reduce the high rate of relapse in Veterans with AUD, it is necessary for interventions to more effectively address the associated neurobiological dysfunction. Non-invasive neuromodulation techniques are showing promise toward the aim of modifying specific and selective neural targets related to AUD and relapse. To date, TMS has been primarily delivered to the dorsolateral and medial prefrontal cortices as these regions are, on average, highly reactive to alcohol cues. On an individual basis, however, peak brain response to alcohol cues can vary substantially in spatial location within the brain. Retrospective analyses of TMS-AUD clinical trails has demonstrated that when TMS is delivered to an individual's peak brain response to alcohol cues, the likelihood of remaining abstinent is increased by a factor of 5.6 (relative to sham TMS treatment). This study aims to deliver one session of TMS to a cortical target which displays peak functional connectivity to the ventral striatum, a key brain region mediating reward and alcohol cue reactivity. The ultimate goal of this study evaluate change in brain reactivity to alcohol cues following active and sham TMS.

### Conditions Module

**Conditions:**

- Alcohol Use Disorder

- Alcohol Abuse

- Alcoholism

- Drinking Behavior

- Drinking Problem

**Keywords:**

- Transcranial Magnetic Stimulation

- Veterans

- Neuroimaging

- Relapse

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Device: Active Transcranial Magnetic Simulation

**Label:** Active fMRI-guided TMS

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Device: Sham

**Label:** Sham fMRI-guided TMS

**Type:** SHAM_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Active fMRI-guided TMS

**Description:** 1 session of active continuous theta burst stimulation (3600 pulses, 110% RMT) will be delivered to the cortical region demonstrating maximal functional connectivity with the striatum during alcohol cue presentation. TMS will be delivered using the Magventure MagPro X100.

**Name:** Active Transcranial Magnetic Simulation

**Other Names:**

- MagVenture MagPro X100

- Continuous Theta Burst Stimulation

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- Sham fMRI-guided TMS

**Description:** 1 session of sham continuous theta burst stimulation (3600 pulses, 110% RMT) will be delivered to the cortical region demonstrating maximal functional connectivity with the striatum during alcohol cue presentation. The MagVenture MagPro x100 is capable of administering a sham stimulation. The reverse side of the TMS coil is plated with a magnetic shield such that electromagnetic energy cannot stimulate the brain. The device offers compatibility with Transcutaneous Electrical Nerve Stimulation devices such that titrated electrical pulses can be delivered to the scalp location to mimic the sensation of a TMS pulse without stimulating the brain.

**Name:** Sham

**Other Names:**

- MagVenture MagPro X100

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** The effect of real versus sham fMRI-guided TMS on alcohol cue reactivity will be assessed by comparing brain reactivity to images of alcohol ('alcohol cues') shown during the fMRI scan. Change in blood-oxygen level dependent signal magnitude will be measured within the striatum, a key brain region involved in cue-reactivity.

**Measure:** Change in blood-oxygen level dependent signal as a measure of change in alcohol cue reactivity

**Time Frame:** Baseline (pre-TMS) and Day 2 (post-TMS)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Between age 25 and 75.
* Current DSM-5 diagnosis of moderate to severe AUD (≥4 diagnostic symptoms).
* Able to attend scheduled clinic visits
* Able to read, understand and voluntarily sign Informed Consent prior to participating in any study-specific procedures or assessments.
* If on a medication regimen, that regimen will be stable for the duration of the study;
* 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
* unstable chronic illness.
* Current or lifetime history of bipolar disorder or psychosis.
* Participation in another concurrent intervention based clinical trial.

**Maximum Age:** 75 Years

**Minimum Age:** 25 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Palo Alto

**Country:** United States

**Facility:** VA Palo Alto Health Care System

**State:** California

**Zip:** 94304

#### Overall Officials

**Official 1:**

**Affiliation:** Palo Alto VA Health Care System

**Name:** Daniel McCalley, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** Researchers who provide a methodologically sound proposal.

**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 with the subject code.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

**IPD Sharing:** YES

**Time Frame:** Three to twelve months after publication

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019973

- Term: Alcohol-Related Disorders

- ID: D000019966

- Term: Substance-Related Disorders

- ID: D000064419

- Term: Chemically-Induced Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC25

- Name: Substance Related Disorders

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M3783

- Name: Alcoholism

- Relevance: HIGH

- As Found: Alcohol Use Disorder

- ID: M3774

- Name: Alcohol Drinking

- Relevance: HIGH

- As Found: Alcohol Use

- ID: M7502

- Name: Drinking Behavior

- Relevance: HIGH

- As Found: Drinking Behavior

- ID: M21842

- Name: Alcohol-Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M21837

- Name: Substance-Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M30302

- Name: Chemically-Induced Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000437

- Term: Alcoholism

- ID: D000000428

- Term: Alcohol Drinking

- ID: D000004327

- Term: Drinking Behavior

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M3777

- Name: Ethanol

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
