Intermittent Theta Burst for the Treatment of Alcohol Use Disorders in Veterans

NCT03291431 | Terminated Results DMC FDA Device

• 1 other identifier: 41896
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the efficacy of intermittent theta burst repetitive transcranial magnetic stimulation (iTBS) as a treatment for Veterans with an alcohol use disorder (AUD) to decrease the exceedingly high rate of relapse associated with this condition. iTBS has demonstrated equivalent efficacy and safety to repetitive transcranial magnetic stimulation employing 10Hz stimulation protocols in treatment of depressive disorders. The advantage of iTBS is that it can be delivered in approximately 5 minutes where conventional 10Hz repetitive transcranial magnetic stimulation (rTMS) protocols are typically 20-25 minutes. It is hypothesized that Veterans with AUD who receive active iTBS applied to the left dorsolateral prefrontal cortex (DLPFC), compared to controls (i.e., Veterans with AUD who receive sham iTBS), will show significant decreases alcohol craving, depressive symptomatology and cigarette consumptions, as well as improved neurocognition, a longer period of abstinence, and a lower overall rate of relapse over 6 months following standard psychosocial treatment for AUD at VA substance treatment clinics. In exploratory analyses, it is also predicted that magnetic resonance measures of left DLPFC glutamate concentration, volume of anterior frontal cortical brain regions, and performance on fMRI tasks interrogating the function of the salience/reward circuits will serve as biomarkers of iTBS treatment response. The goal of this proposal is to implement treatment that effectively promotes sustained abstinence in Veterans with AUD, given long-term abstinence is related to optimal neurobiological, neuropsychological and psychosocial recovery and functioning.

Conditions

Alcohol Use Disorder; Depressive Disorder; Cigarette Smoking

Keywords

alcohol use disorder; intermittent theta burst; Veterans; depressive disorder; cigarette smoking

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Were Abstinent Through Month 6

  Number of particiants in active vs. sham who maintained completed abstinence from alcohol/substance over 6 months post final rTMS session.

  6 months

Secondary Outcomes (4)

• Left Dorsolateral Prefrontal Region Glutamate/Creatine Ratio

  baseline and follow-up (approximately 2 weeks)

• Left Dorsolateral Prefrontal Cortex Thickness

  baseline and follow-up (approximately 2 weeks)

• General Depressive Symptoms

  baseline and follow-up (approximately 2 weeks)

• Anhedonic Depressive Symptoms

  baseline and follow-up (approximately 2 weeks)

Study Arms (2)

Active iTBS

ACTIVE COMPARATOR

Participants will be randomized to active or sham iTBS.

Device: Intermittent theta burst transcranial magnetic stimulation

Sham iTBS

SHAM COMPARATOR

Participants will be randomized to active or sham iTBS.

Device: Intermittent theta burst transcranial magnetic stimulation

Interventions

Intermittent theta burst transcranial magnetic stimulation DEVICE

20 iTBS sessions (active or sham) administered over the course of 2 weeks

Active iTBS; Sham iTBS

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for alcohol use disorder, and alcohol is self-identified as primary substance of misuse.
• Actively in treatment at VA Palo Alto HCS Addiction Treatment Service
• Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form prior to participation in study procedures.

You may not qualify if:

• History of Schizophrenia Spectrum Disorders, Bipolar Disorders, a
• Current substance use disorder that exceeds the severity of the AUD (based on DSM-5 diagnostic criteria)
• Current use of an FDA approved medication (i.e., disulfiram, acamprosate, and naltrexone) for treatment of AUD,
• Active current suicidal intent or plan (patients with a previous clinical flag for risk for suicide will be required to have an established safety plan involving their primary psychiatrist and the treatment team before entering the clinical trial),
• Any form of previous TMS or electroconvulsive treatment.
• Thyroid disease,
• Unstable congestive heart failure, angina, other severe cardiac illness as defined by treatment regimen changes in the prior 3 months
• Cerebrovascular accident
• Cancer if \< 1 year since end of treatment
• Unstable diabetes
• COPD requiring oxygen supplementation
• Alzheimer's disease
• Parkinson's disease
• Any Biomedical implants with ferromagnetic content
• Neurostimulation devices, cardiac pacemakers or any magnetic resonance contraindications

Sponsors & Collaborators

• Stanford University: lead

Study Sites (2)

Palo Alto VA Health Care System

Palo Alto, California, 94304, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (1)

• Durazzo TC, McNerney MW, Hansen AM, Gu M, Sacchet MD, Padula CB. BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex. Drug Alcohol Depend. 2023 Jul 1;248:109901. doi: 10.1016/j.drugalcdep.2023.109901. Epub 2023 Apr 28.

  PMID: 37146499 DERIVED

MeSH Terms

Conditions

Alcoholism; Depressive Disorder; Cigarette Smoking

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Mood Disorders; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Limitations and Caveats

The study was terminated early before enrolling the planned number of participants, therefore the data analysis is underpowered.

Results Point of Contact

• Title: Dr. Timothy C. Durazzo/Project PI
• Organization: Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences

tdurazzo@stanford.edu

650-493-5000

Study Officials

• Timothy C Durazzo, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 25, 2017
• Study Start: December 1, 2017
• Primary Completion: January 30, 2022
• Study Completion: July 30, 2022
• Last Updated: October 16, 2023
• Results First Posted: June 22, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)