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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
17
20 iTBS sessions (active or sham) administered over the course of 2 weeks
Palo Alto VA Health Care System
Palo Alto, California, United States
Stanford University
Stanford, California, United States
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.
Time frame: 6 months
Left Dorsolateral Prefrontal Region Glutamate/Creatine Ratio
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.
Time frame: baseline and follow-up (approximately 2 weeks)
Left Dorsolateral Prefrontal Cortex Thickness
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.
Time frame: baseline and follow-up (approximately 2 weeks)
General Depressive Symptoms
Beck Depression Inventory-II score pre and post active/sham iTBS (score range, 0 to 63, higher scores indicate more severe symptoms).
Time frame: baseline and follow-up (approximately 2 weeks)
Anhedonic Depressive Symptoms
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).
Time frame: baseline and follow-up (approximately 2 weeks)
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