TMS for Alcoholism

Overseen By Rhia Walton

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Naltrexone, Acamprosate, Topiramate, others

Disqualifiers: Seizures, Alcohol withdrawal, Brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 15

Duration: 4 weeks

86 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that participants do not take certain medications known to improve alcohol treatment outcomes, like naltrexone, acamprosate, or topiramate, and psychiatric/sleeping medications, except for stable antidepressants/SSRIs. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment MPFC Theta Burst Stimulation for alcoholism?

Research shows that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can reduce brain reactivity to alcohol cues and decrease drinking behavior in people with alcohol use disorder. Additionally, TBS has been effective in reducing cravings for other substances, like methamphetamine, suggesting its potential for treating addiction. ^{1 2 3 4 5}

Is TMS with Theta Burst Stimulation safe for humans?

Research shows that TMS with Theta Burst Stimulation is generally well-tolerated in humans, with occasional mild side effects like headaches. In one study, a participant experienced a temporary neurological event, but overall, the treatment was considered safe for use in conditions like cocaine use disorder. ^{1 2 3 4 6}

How is MPFC Theta Burst Stimulation different from other treatments for alcoholism?

MPFC Theta Burst Stimulation is unique because it uses a non-invasive technique called transcranial magnetic stimulation (TMS) to target the medial prefrontal cortex, which may help reduce brain reactivity to alcohol cues and decrease drinking behavior. This method is shorter in duration and potentially more tolerable than traditional repetitive TMS, making it a promising option for treating alcohol use disorder. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for adults aged 21-65 who drink heavily, meeting specific criteria (over 14 drinks per week for women and over 21 for men). Participants must have Alcohol Use Disorder as defined by DSM-V. Exclusions include unstable medical conditions, metal implants above the neck, pregnancy or inadequate birth control use, certain psychiatric disorders, history of severe head injury or substance abuse other than nicotine.

Inclusion Criteria

Alcohol Use Disorder determined by DSM-V criteria using the Structured Clinical Interview for DSM-V

I am between 21 and 65 years old.

I drink more than the recommended weekly limit and have heavy drinking days.

Exclusion Criteria

Has metal placed above the neck

Meets DSM V criteria for specific disorders

I am not pregnant, nursing, or I am using reliable birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive theta burst stimulation (TBS) to the medial prefrontal cortex (mPFC) over 4 weeks, with 36 sessions (3x/day on each of 3 days/week)

4 weeks

12 visits (in-person)

Follow-up

Participants are monitored for changes in drinking behavior and brain reactivity to alcohol cues over a 3-month period

3 months

3 visits (in-person)

Treatment Details

Interventions

• MPFC Theta Burst Stimulation

Trial Overview The study tests theta burst stimulation (TBS) to the medial prefrontal cortex (mPFC) using transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique. It aims to see if TBS can reduce alcohol cravings and alter responses to alcohol-related cues. Participants will receive either real TBS or a sham procedure as a control.

Participant Groups

Group I: Real TBS to the mPFC Experimental Treatment 1 Intervention

For continuous theta burst stimulation (cTBS), participants will receive 3 sessions of stimulation per visit over the left medial prefrontal cortex (mPFC) (each train: 3 pulse bursts presented at 5Hz, 15 pulses/sec, 600 pulses/session, 60 sec intertrain interval; 120% RMT, MagPro; 10-15 min inter session interval) using a figure 8 coil (Coil Cool-B65 A/P).

Group II: Sham TBS to the mPFC Placebo Group 1 Intervention

The MagVenture MagPro system has an integrated, active sham which passes current through two surface electrodes placed on the scalp. The electrodes will be placed on the left frontalis muscle for all sessions. A patient identification card will randomize participants to receive either real or sham stimulation. This system maintains blinding by a gyroscope in the coil which indicates to the clinical staff whether the coil should be rotated up or down for this participant once the card is entered into the machine. One side of the coil is active, the other is sham. The integrity of the double-blind procedure will be assessed by asking the patients and study personnel rate their confidence regarding whether they thought they received real or sham (scale 1-10).

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

In a clinical trial with 50 individuals suffering from alcohol use disorder (AUD), continuous theta burst stimulation (TBS) to the medial prefrontal cortex significantly reduced drinking behavior and brain reactivity to alcohol cues for up to 3 months after treatment.

Participants receiving real TBS were 2.71 times more likely to stay in the study and 3.09 times more likely to remain sober compared to those receiving sham treatment, indicating the potential efficacy of TBS as a therapeutic intervention for AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study. McCalley, DM., Kaur, N., Wolf, JP., et al.[2023]

Intermittent theta burst stimulation (iTBS) over the left DLPFC and continuous theta burst stimulation (cTBS) over the right DLPFC significantly reduced cue-induced craving in abstinent methamphetamine-dependent subjects, indicating their potential efficacy as treatments for addiction.

The study involved 83 participants and showed that while iTBS had higher self-reported adverse effects initially, both stimulation methods were feasible and tolerable, suggesting a promising approach to reduce craving with shorter treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study. Zhao, D., Li, Y., Liu, T., et al.[2023]

Intermittent theta burst stimulation (iTBS) was found to be safe for veterans with PTSD, even those with mild alcohol use disorder (AUD), although AUD patients reported more adverse events.

Patients with comorbid AUD who received active iTBS showed greater improvement in depression symptoms compared to those without AUD, while the presence of AUD did not affect changes in PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation in Veterans with Mild Alcohol Use Disorder. Bozzay, ML., Brigido, S., van 't Wout-Frank, M., et al.[2022]

A randomized controlled trial involving 60 patients with alcohol use disorder is investigating the efficacy of intermittent theta burst stimulation (iTBS) on reducing cravings, targeting the left dorsolateral prefrontal cortex (DLPFC).

The study aims to determine if iTBS can effectively decrease craving levels, as measured by visual analogue scale (VAS) scores, and if successful, it could offer a tolerable and accessible treatment option for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Intermittent Theta Burst Stimulation (iTBS) in Patients With Alcohol Use Disorder: Study Protocol for a Randomized Controlled Trial. Yuan, C., Su, H., Chen, T., et al.[2022]

In a study involving 49 substance-dependent individuals (25 cocaine users and 24 alcohol users), continuous theta burst stimulation (cTBS) to the left frontal pole significantly reduced brain activity in regions associated with drug cues, such as the orbitofrontal cortex and caudate, indicating a potential mechanism for reducing cravings.

The results suggest that cTBS may effectively dampen neural circuits activated by drug-related stimuli in both cocaine and alcohol users, but further research is needed to assess the long-term effects on brain function and substance use behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users. Hanlon, CA., Dowdle, LT., Correia, B., et al.[2022]

A proof-of-concept study involving 19 individuals with cocaine use disorder showed that administering intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex was well-tolerated and safe, even in participants actively using cocaine.

Participants who completed at least 26 of the 30 iTBS sessions reduced their weekly cocaine use by 78% in spending and 70% in frequency, indicating that iTBS may effectively modulate addiction-related circuits and reduce substance use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. Steele, VR., Maxwell, AM., Ross, TJ., et al.[2020]

Intermittent theta burst stimulation (iTBS) of the prefrontal cortex has shown effects on reducing cocaine craving and consumption that are comparable to traditional high-frequency rTMS (15 Hz) in a study of 25 treatment-seeking cocaine addicts.

Both iTBS and 15 Hz rTMS demonstrated similar safety and tolerability profiles, with low dropout rates, suggesting that iTBS could be a more efficient treatment option due to its shorter duration (3 minutes) compared to the 15-minute standard protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. Sanna, A., Fattore, L., Badas, P., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation in Veterans with Mild Alcohol Use Disorder. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Effect of Intermittent Theta Burst Stimulation (iTBS) in Patients With Alcohol Use Disorder: Study Protocol for a Randomized Controlled Trial. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta-Burst Stimulation as a Treatment for Cocaine Use Disorder: A Proof-of-Concept Study. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. [2020]