Developing Functional Connectivity-Guided TMS for Alcohol Use Disorder

May 9, 2024 updated by: Daniel McCalley, VA Palo Alto Health Care System
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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active fMRI-guided TMS
Device: Active Transcranial Magnetic Simulation
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.
Other Names:
  • MagVenture MagPro X100
  • Continuous Theta Burst Stimulation
Sham Comparator: Sham fMRI-guided TMS
Device: Sham
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.
Other Names:
  • MagVenture MagPro X100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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.
Baseline (pre-TMS) and Day 2 (post-TMS)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Palo Alto Health Care System

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Stanford University

Investigators

  • Principal Investigator: Daniel McCalley, PhD, Palo Alto VA Health Care System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

May 9, 2024

First Submitted That Met QC Criteria

May 9, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 9, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PADNEW_0003

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 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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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