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

Not Applicable

Terminated

• Conditions: Alcohol Use Disorder; Depressive Disorder; Cigarette Smoking
• Interventions: Device: Intermittent theta burst transcranial magnetic stimulation

• Registration Number: NCT03291431
• Lead Sponsor: Stanford University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-09-19
• Study First Submitted QC: 2017-09-19
• Study First Posted: 2017-09-25
• Study Start: 2017-12-01
• Primary Completion: 2022-01-30
• Study Completion: 2022-07-30
• Results First Submitted: 2023-02-24
• Results First Submitted QC: 2023-06-20
• Results First Posted: 2023-06-22
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• 21-65 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.

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Exclusion Criteria

• 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
• Traumatic brain injury with self-reported or observed loss of consciousness > 30 minutes
• Any primary or traumatically induced seizure disorder
• Lack of fluency in English, Wechsler Adult Reading Test below the 7th percentile (i.e., moderate or greater impairment in estimated general intelligence),
• Females who are pregnant or actively attempting pregnancy (conservative exclusion for magnetic resonance research),
• Current use of any medication or substance that is documented to lower seizure threshold or has been identified as a contraindication for TMS treatment.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham iTBS	Intermittent theta burst transcranial magnetic stimulation	Participants will be randomized to active or sham iTBS.
Active iTBS	Intermittent theta burst transcranial magnetic stimulation	Participants will be randomized to active or sham iTBS.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Were Abstinent Through Month 6	6 months	Number of particiants in active vs. sham who maintained completed abstinence from alcohol/substance over 6 months post final rTMS session.

Secondary Outcome Measures

Name	Time	Method
Left Dorsolateral Prefrontal Region Glutamate/Creatine Ratio	baseline and follow-up (approximately 2 weeks)	Left dorsolateral prefrontal region glutamate/creatine ratio pre and post active/sham iTBS. Data were recorded in international units (IU) and converted to Z scores based on the entire sample (unit normal distribution, mean of 0, standard deviation of 1). Higher Z scores (standard deviation above the mean) indicate a greater metabolite concentration ratio and better functioning.
General Depressive Symptoms	baseline and follow-up (approximately 2 weeks)	Beck Depression Inventory-II score pre and post active/sham iTBS (score range, 0 to 63, higher scores indicate more severe symptoms).
Anhedonic Depressive Symptoms	baseline and follow-up (approximately 2 weeks)	Anhedonic depressive symptoms from Mood and Anxiety Symptom Questionnaire (MASQ, 30-item version; score range: 10 to 50, high scores correspond to more severe symptoms).
Left Dorsolateral Prefrontal Cortex Thickness	baseline and follow-up (approximately 2 weeks)	Left dorsolateral prefrontal cortex thickness pre and post active/sham iTBS; hypothesized that increased thickness corresponds to improved cytoarchitectural integrity of the left dorsolateral prefrontal cortex.

Trial Locations

Locations (2)

Stanford University; 🇺🇸 Stanford, California, United States

Palo Alto VA Health Care System; 🇺🇸 Palo Alto, California, United States