MPFC Theta Burst Stimulation as a Treatment Tool for Alcohol Use Disorder: Effects on Drinking and Incentive Salience

Overview

The purpose of this study is to develop transcranial magnetic stimulation (TMS), specifically TMS at a frequency known as theta burst stimulation (TBS), to see how it affects the brain and changes the brain's response to alcohol-related pictures. TMS and TBS are stimulation techniques that use magnetic pulses to temporarily excite specific brain areas in awake people (without the need for surgery, anesthetic, or other invasive procedures). TBS, which is a form of TMS, will be applied over the medial prefrontal cortex, (MPFC), which has been shown to be involved with drinking patterns and alcohol consumption. This study will test whether TBS can be used as an alternative tool to reduce the desire to use alcohol and reducing the brain's response to alcohol-related pictures.

Detailed description

With advances in optogenetic stimulation techniques, preclinical studies have demonstrated that activity in frontal-striatal neural circuits has a causal influence on heavy drinking and alcohol reinstatement. Clinically, however, this research has not yet been translated into a neural circuit based therapeutic technique for patients with alcohol use disorder (AUD). The long term goal of this multidisciplinary research study team is to determine the optimal parameters through which non-invasive transcranial magnetic stimulation can be used to improve alcohol drinking outcomes (abstinence, heavy drinking days) among individuals seeking behavioral treatment for AUD. Building on a foundation of several target identification studies and a small double-blinded clinical trial in treatment-engaged AUD patients performed by the study team in the Charleston Alcohol Research Center, here the investigator proposes a double-blind placebo controlled, randomized study to evaluate the efficacy of theta burst stimulation (TBS) to medial prefrontal cortex (mPFC) as a tool to decrease drinking and brain reactivity to alcohol cues among treatment-seeking individuals with AUD. Individuals will be screened initially by the Clinical Intake and Assessment core, then given an opportunity to enroll in this study, provide informed consent, and be randomized to receive real or sham TBS to the mPFC 36 sessions (3x/day on each of 3 days/week over 4 weeks, i.e., 12 days). The scientific premise of this 5 year proposal is that, by modulating the neural circuits that regulate alcohol cue-reactivity it will be possible to increase alcohol abstinence rates and decrease heavy drinking days over a 4 month period. With the combined scientific expertise in brain stimulation, neuroimaging, alcohol use disorder research in the Charleston Alcohol Research Center, and clinical practice at MUSC, the study team is uniquely suited to develop this critical line of research. The outcomes of the proposed Aims will provide an evidence-based foundation for a multisite clinical trial and will hasten progress towards developing a new neural circuit based treatment for patients with AUD.

Interventions

• Device Real TBS to the mPFC
  This will be delivered with the Magventure Magpro system; 600 pulses of continuous theta burst stimulation with the active sham coil (double blinded using the integrated active sham system).
• Device Sham TBS to the mPFC
  This will be delivered with the Magventure Magpro system; 600 pulses with the active sham coil (double blinded using the integrated active sham system). The MagVenture MagPro system has an integrated active sham that passes current through two surface electrodes placed on the scalp. The electrodes are placed on the left frontalis muscle under the coil for both the real and sham stimulation sessions.

Primary outcome measures

• Change in Percent Heavy Drinking Days (PHDD) from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)]
• Change in Percent Days Abstinent (PDA) from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)]
• Change in alcohol cue task MRI activation 1-week post treatment from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline)]

Secondary outcome measures (6)

• Change in anxiety via State-Trait Anxiety Inventory from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)]
• Change in alcohol use via Obsessive-Compulsive Drinking Scale from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)]
• Change in depression via Becks Depression Inventory-II from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)]
• Change in alcohol use via Alcohol Audit from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline), 1-month post treatment (Follow-up #1), 2-months post treatment (Follow-up #2), 3-months post treatment (Follow-up #3)]
• Changes in cognitive performance from baseline [Time frame: Baseline (Week 1), Post-treatment (4-weeks from baseline)]
• Changes in Snaith-Hamilton Pleasure Scale from baseline [Time frame: Baseline (Week 1), Weekly throughout treatment (Weeks 1-4), Post-treatment (4-weeks from baseline)]

Eligibility criteria

Inclusion criteria

• Age 21-65 (to maximize participation; note: Scalp-to-Cortex distance will be included as a covariate to calculate adjusted TMS dose given expected cortical atrophy in heavy alcohol users and older adults and the demonstrated effect50 on TMS-fMRI responses in addiction)
• Alcohol Use Disorder, determined by DSM-V criteria, using the Structured Clinical Interview for DSM-V
• Consumption of more than 14 drinks (women) or 21 drinks (men) per week, with at least 4 heavy drinking days (defined as ≥ 4 drinks for women and ≥ 5 for men) per week during the 30-days prior to enrolling.
• Able to read and understand questionnaires and informed consent.

Exclusion criteria

• Has metal placed above the neck
• Is at elevated risk of seizure (i.e., has a history of seizures, is currently prescribed medications known to lower seizure threshold)
• Has a history of moderate to severe alcohol withdrawal or medicated alcohol withdrawal
• Has a history of claustrophobia
• Has a history of chronic migraines
• Has a history of traumatic brain injury, including a head injury that resulted in hospitalization, loss of consciousness for more than 10 minutes, or having ever been informed that they have an epidural, subdural, or subarachnoid hemorrhage
• Has an unstable medical illness requiring planned medical/surgical intervention (e.g. chemotherapy, surgical procedure)
• Medications: Is currently taking or initiates a new prescription for drugs known to improve alcohol drinking treatment outcomes (e.g. naltrexone, acamprosate, topiramate) or taking psychiatric/sleeping medications except for stable (1 month) antidepressants/SSRI's. \[Note: this criterion is for scientific rather than safety or patient comfort reasons\].
• Has a history of substance use disorder (other than nicotine) by DSM-V criteria in the past 6 months
• Meets DSM V criteria for panic disorder, bipolar disorder, obsessive-compulsive disorder, schizophrenia, dissociative disorders, eating disorders, and any other psychotic disorder. \[Note: The inclusion of participants with other affective and anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with AUD at large\]
• Has current suicidal ideation or homicidal ideation
• Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Medical University of South Carolina — Charleston

Identifiers

NCT: NCT04998916 · 00102709 · 2P50AA010761-26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗