Last updated on July 2020

Theta Burst Stimulation as a Tool to Decrease Drinking in Treatment-seeking Alcohol Users

Brief description of study

There is growing interest in the utilization of transcranial magnetic stimulation (TMS) as a novel, non-pharmacologic approach to decreasing alcohol use among treatment-seeking individuals with Alcohol Use Disorder (AUD). The results of this study will be used to determine which of the 2 proposed TMS strategies has a larger effect on drinking behavior (% days abstinent, % heavy drinking days) as well as alcohol cue-reactivity in a 4 month period. These data will pave the way for TMS to be used as an innovative, new treatment option for individuals with AUD.

Detailed Study Description

Alcohol Use Disorder (AUD) is prevalent, devastating, and difficult to treat. The majority of the therapeutic approaches available to date have relied on pharmaceutical modulation or and/or psychotherapy. With a growing knowledge of the neural circuits that contribute to relapse in AUD, there is an emerging interest in developing a novel, neural-circuit specific therapeutic tool to enhance AUD treatment outcomes. The long term goal of the multidisciplinary research team is to develop an evidence-based brain stimulation treatment protocol which will improve AUD treatment outcomes. The competing neurobehavioral decision systems (CNDS) theory posits that in addiction, choice results from a regulatory imbalance between two decision-making systems (impulsive and executive) (25-27). These behavioral systems are functionally linked to two discrete frontal- striatal circuits which regulate limbic and executive control (28). Modulating these competing neural circuits (e.g. either dampening the limbic/impulsive system or amplifying the executive control system) may render alcohol users less vulnerable to relapse (43). These two frontal-striatal neural circuits - the limbic loop (ventromedial prefrontal cortex (vmPFC)-ventral striatum), and executive control loop (dorsolateral prefrontal cortex (dlPFC)-dorsal striatum) can be differentially stimulated by theta burst stimulation (TBS), a patterned form of transcranial magnetic stimulation (TMS) (15). Continuous TBS (cTBS) results in long term depression (LTD) of cortical excitability and intermittent TBS (iTBS) results in long term potentiation (LTP) (14).

Over the past 7 years, through the scaffolding of a National Institute on Alcohol Abuse and Alcoholism (NIAAA) P50 Center and a strong Brain Stimulation Research program, the multidisciplinary group of clinicians and neuroscientists have demonstrated 1) it is possible to differentially activate these circuits through TMS/Blood oxygenation level dependent (BOLD) imaging (15), 2) LTD-like TMS (cTBS) to the vmPFC (Strategy 1) decreases orbitofrontal cortex and ventral striatal/accumbens BOLD signal in heavy alcohol users (14), 3) cTBS also decreases alcohol cue reactivity in this population (17), and 4) in AUD patients currently enrolled in intensive outpatient treatment, 10 days of cTBS to the vmPFC is feasible, well-tolerated, increases 1 and 2 month retention rates, and attenuates limbic brain reactivity to alcohol cues after 1 month (17). While these studies provide a strong foundation for pursuing a larger multisite trial of cTBS, the CNDS theory and other alcohol TMS studies suggests that the dlPLC may also be a fruitful treatment target (25-27). Recently, a sham-controlled pilot study compared the efficacy of vmPFC cTBS (Strategy 1) to dlPFC iTBS (Strategy 2), and demonstrated that a single session of dlPFC iTBS had a greater effect on the brain response to alcohol cues that vmPFC cTBS (15). To resolve this gap in the literature, this protocol will propose a randomized, double-blind, sham-controlled clinical trial to evaluate the relative efficacy of these 2 strategies as novel tools to improve AUD treatment outcomes (e.g. percent days abstinent up to 4 months after treatment initiation). These outcomes will be measured with urine ethyl glucuronide (ETG) and carbohydrate-deficient transferrin (CDT) measurements. The brain reactivity to alcohol will also be used to evaluate the effect of these TBS treatments. The long-term vision is that TBS would be used as an adjuvant to behavioral treatment, enabling individuals to maximize the likelihood of behavioral change.

180 treatment-seeking men and women enrolled in Wake Forest University (WFU) associated clinics, including the Department of Psychiatry Outpatient Program and Comprehensive Cancer Center, will be randomized to receive 20 sessions (2x/day; 10 days, 20 min intersession interval) of either real or sham TBS to the vmPFC (Aim 1, Strategy 1) of left dlPFC (Aim 2, Strategy 2) while they are enrolled in the outpatient treatment program. Randomization will occur during the 1st week of the outpatient program. Real/Sham TBS will be delivered immediately before their outpatient therapy visit during weeks 2 & 3 of the program. Quantitative ETG will be collected daily. ETG and CDT will be collected monthly for 4 months. Additional assessments and brain reactivity to alcohol cues will be measured at 4 time points: before TMS treatment (Outpatient program, week 1), after TMS treatment (week 5), and at the 3 monthly Follow Up visits. Building on recent pilot data, the investigators will test the hypotheses that for both Strategy 1 & 2, real TBS will improve AUD treatment outcomes significantly more than sham. Analysis will be performed using repeated measures analysis of variance (ANOVA) on change scores from baseline for each visit. The main independent variable in the ANOVA will be time (visits on day 1, 6, 10), group (vmPFC vs. dlPFC TBS vs. sham) and their interaction.

Aim 1 (Strategy 1): Modulating the limbic system: vmPFC cTBS. The investigators will evaluate effect of vmPFC cTBS, relative to sham, on number of days abstinent (primary outcome) and heavy drinking days in 30 day intervals for 4 months. Participants will receive stimulation over the left frontal pole (EEG 10-20 system: FP1). This location has been used in previous studies in alcohol users which demonstrate vmPFC target engagement.

Aim 2 (Strategy 2): Modulating the executive system: dlPFC iTBS. The investigators will evaluate the effect of dlPFC iTBS, relative to sham, on the parameters listed. iTBS will be delivered over the left dlPFC (EEG 10-20 system: F3) as this location has also been validated to reliable result in target engagement by the investigators.

Exploratory Aim- Baseline alcohol cue reactivity as a mediator of TBS clinical response. The investigators will test the hypotheses that individuals with a higher ratio of (dlPFC-striatal)/(vmPFC-striatal) response to alcohol cues will be more likely to have a change in drinking after Strategy 2.

Clinical Study Identifier: NCT04154111

Find a site near you

Start Over

Wake Forest School of Medicine

Winston-Salem, NC United States
  Connect »

Recruitment Status: Open

Brief Description Eligibility Contact Research Team

Volunteer Sign-up

Sign up for our FREE service to receive email notifications when clinical trials are posted in the medical category of interest to you.