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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a non-invasive brain treatment called transcranial magnetic stimulation (TMS) to determine its effectiveness in reducing alcohol cravings. TMS uses magnetic pulses to stimulate specific brain areas linked to drinking behavior. The study will test TMS, specifically MPFC Theta Burst Stimulation, on individuals who drink heavily and have an alcohol use disorder, examining its impact on their reaction to alcohol-related images. Participants should consume more than 14 drinks a week for women or 21 for men and experience frequent heavy drinking days. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research on innovative treatments for alcohol use disorder.

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 prior data suggests that TMS and TBS are safe for use in humans?

Research has shown that theta burst stimulation (TBS) applied to the medial prefrontal cortex (MPFC) is generally well-tolerated. In one study, participants received this treatment for ten days and found it manageable, experiencing no major negative side effects. The study also found that TBS reduced alcohol consumption and lessened the brain's response to alcohol-related cues for up to three months. This suggests the treatment offers potential benefits and is safe for short-term use.

Overall, current evidence supports using this non-invasive brain stimulation for treating alcohol use disorder, indicating it is a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using MPFC Theta Burst Stimulation (TBS) for alcoholism because it employs a cutting-edge technique called continuous theta burst stimulation directly to the brain's medial prefrontal cortex (mPFC). Unlike standard treatments like medications or behavioral therapy, TBS offers a non-invasive approach that targets specific brain areas involved in addiction. This method uses rapid, repetitive magnetic pulses to potentially alter brain activity linked to alcohol cravings, providing a novel way to address the underlying neurological aspects of alcoholism. The precision and non-invasive nature of TBS make it a promising new avenue for those seeking alternatives to traditional therapies.

What evidence suggests that MPFC Theta Burst Stimulation is effective for reducing alcohol cravings?

Research shows that MPFC Theta Burst Stimulation (TBS) may help reduce alcohol consumption. In this trial, participants will receive either real TBS or sham TBS to the medial prefrontal cortex. Earlier studies found that ten days of TBS treatment on the medial prefrontal cortex (a part of the brain linked to drinking habits) led to less drinking and a reduced brain response to alcohol-related cues. These effects lasted for up to three months after starting treatment. This suggests that TBS might help decrease the desire for alcohol by changing how the brain reacts to alcohol-related images. Early findings also indicate that TBS is generally well tolerated, meaning participants usually don't experience significant negative effects. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10140456/

Medial Prefrontal Cortex Theta Burst Stimulation Improves ... Ten days of MPFC TBS is well tolerated, reduces drinking, and decreases brain reactivity to alcohol cues for up to 3 months after treatment initiation.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04998916

MPFC Theta Burst Stimulation as a Treatment Tool ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37124360/

Medial Prefrontal Cortex Theta Burst Stimulation ... - PubMed Conclusions: Ten days of MPFC TBS is well tolerated, reduces drinking, and decreases brain reactivity to alcohol cues for up to 3 months after ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2451902224003768

A Randomized Controlled Trial of Medial Prefrontal Cortex ... This early-stage trial demonstrates that TBS to the MPFC reduces brain reactivity to cocaine cues in key nodes of the salience network in treatment-seeking ...

5. biologicalpsychiatrycnni.org biologicalpsychiatrycnni.org/article/S2451-9022(24)00376-8/abstract

A Randomized Controlled Trial of Medial Prefrontal Cortex ... Theta burst stimulation (TBS) to the left frontal pole of the medial prefrontal cortex (MPFC) has previously been shown to reduce drinking and brain reactivity ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301382X

Non-invasive Brain Stimulation for Alcohol Use Disorders Currently available data generally supports the use of non-invasive brain stimulation as a near-term treatment for alcohol use disorder.

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00210/full

The Effect of Intermittent Theta Burst Stimulation (iTBS) in ... This study is a randomized controlled trial to investigate the efficacy of left DLPFC iTBS in a population of alcohol use disorder patients, compared with sham ...