Deep Repetitive Transcranial Magnetic Stimulation for Alcohol Use Disorder

Exploration of the Potential Role of Anterior Cingulate (ACC) dTMS in Relapse to Alcohol Use

dTMS intervention to reduce recurrent alcohol abuse among alcohol users who are abstinent for at least 5 days.

Study Overview

• Status: Completed
• Conditions: Alcohol Abuse
• Intervention / Treatment: Device: Active dTMS; Device: Sham dTMS

Detailed Description

Phase 1: (up to 2 weeks), participants undergo a set of baseline assessments, including questionnaires, rating scales, and resting state functional magnetic resonance imaging (rsfMRI).

Phase 2, patients receive one of two treatments: High-frequency (10Hz, 100 trains of 3 sec with 15 sec inter train interval) dTMS targeting the ACC or sham stimulation for 30 min. Each treatment is preceded by provocation (pouring, holding and smelling the subject's favorite alcoholic beverage) designed to activate the relevant brain circuitry (provocation of symptoms may increase response rate to Deep TMS as was evident in the treatment of PTSD, cigarette smoking and OCD). dTMS sessions are conducted five times per week for 3 weeks, for a total of 15 sessions. A second scan that include rsfMRI and a risk-related decision-making task is conducted at the end of this phase.

Phase 3 includes 12 weeks of patients' follow-up, including clinical visits at weeks 1, 2, 4, 8 and 12 post treatment. During this phase, subjective and objective measures of alcohol use (self-report and analysis of urine samples for levels of ethyl glucuronide (EtG) and ethyl sulfate (EtS), respectively) are collected. Following completion of the main part by the individual, an "open label" treatment using the same parameters of the experiment is offer (regardless of treatment group).

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 - 65
• Current diagnosis of alcohol dependence
• Alcohol use in the past month
• Right handed (self-report)
• If female, negative urine pregnancy test
• If female, must either agree to practice an effective birth control method; agree to abstinence from intercourse; be surgically sterile or postmenopausal for at least one year

Exclusion Criteria:

• Currently pregnant or breastfeeding
• More than mild cognitive impairment, as determined by a score on the Montreal cognitive assessment (MoCA) <25.
• Current diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder
• Use in the past 2 weeks of medication or illicit drug with known high pro-convulsant action, as self-reported, or detected using urine toxicology screening; and with accordance to the Physician best Judgment.
• Any history of clinically significant neurological disorders, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery or personal history of head trauma that resulted in loss of consciousness for > 5 minutes and retrograde amnesia for > 30 minutes (self-reported history).
• Any history of seizures other than febrile childhood seizures (self-reported history)
• Clinically significant hearing impairment
• Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces). Eligibility will be determined by the "MRI Safety Screening Questionnaire" and verified, if necessary, by a radiology consultant. Some of the patients that will be excluded from the imaging part of the study will be included in the clinical part.
• Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the investigators and after any consults if indicated, participation in the study is not in the best interest of the patient.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study group; alcoholics - dTMS group	Device: Active dTMS; dTMS to ACC
Sham Comparator: control group; alcoholics - sham group	Device: Sham dTMS; SHAM - no stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol usage	The percentage of heavy drinking days (pHDD; 4+ alcohol units per women and 5+ for men, within one day) between the active and sham groups over the follow up period.	12 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol craving	The scores of the Penn alcohol craving scale (PACS) between the active and sham groups over the follow up period. The PACS is a 5-item questionnaire that measures the individual's alcohol craving in the past week, with each item scored on a scale between 0 and 6 (i.e., minimum value of 0 and maximum value of 30) and higher scores denote higher levels of craving.	12 weeks post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modifications to brain volume	Changes to volumes (cm3) of brain areas that are implicated in alcohol abuse pathophysiology, as measured by MRI from pre- to post-treatment between the active and sham groups.	3 weeks of treatment
Modifications to functional connectivity	Changes to functional connectivity (correlation coefficient) of networks that are implicated in alcohol abuse pathophysiology, as measured by resting state fMRI from pre- to post-treatment between the active and sham groups	3 weeks of treatment
Modifications to blood-oxygen-level-dependent (BOLD) signal	Changes to blood-oxygen-level-dependent (BOLD) signal (arbitrary units) of brain areas that are implicated in alcohol abuse pathophysiology during behavioral tasks, as measured by fMRI following treatment between the active and sham groups.	3 weeks of treatment

Collaborators and Investigators

• Sponsor: Soroka University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: February 7, 2016
• First Submitted That Met QC Criteria: February 21, 2016
• First Posted (Estimate): February 25, 2016

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 27, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism
• Other Study ID Numbers: sor040415ctil

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO