Transcranial Magnetic Stimulation for Alcoholism

Overseen By Michiyah Kimber

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

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

Disqualifiers: Psychoactive substance use, Schizoaffective disorder, Suicidal ideation, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people reduce alcohol use through transcranial magnetic stimulation (TMS). The researchers aim to determine if TMS can increase alcohol-free days and reduce heavy drinking days over four months. Participants will receive either real or sham (fake) TMS sessions to identify the most effective method. This trial suits individuals who struggle with Alcohol Use Disorder and have a history of frequent drinking. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to new treatment options.

Will I have to stop taking my current medications?

If you are currently taking medications that affect alcohol intake or craving, like disulfiram, naltrexone, acamprosate, or topiramate, you will need to stop taking them to participate in this trial. The protocol does not specify about other medications, so it's best to discuss your specific situation with the trial coordinators.

What prior data suggests that transcranial magnetic stimulation is safe for individuals with Alcohol Use Disorder?

Research has shown that Theta Burst Stimulation (TBS) is generally well-tolerated by people with Alcohol Use Disorder (AUD). When applied to the dorsolateral prefrontal cortex (dlPFC), studies have found it can improve treatment outcomes without significant side effects. This method has successfully helped veterans reduce alcohol consumption.

Similarly, TBS targeting the medial prefrontal cortex (mPFC) also shows promise. Previous studies report that it is well-tolerated, with participants drinking less and showing reduced brain response to alcohol-related cues. These positive effects can last up to three months after treatment begins.

Overall, both TBS methods appear safe for people with AUD based on current research. While no treatment is completely without risk, available evidence suggests that TBS does not cause serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for alcoholism involve medication or behavioral therapy, but Theta Burst Stimulation (TBS) offers a unique approach by using magnetic fields to target specific brain regions. Researchers are excited about TBS because it focuses on the brain's prefrontal cortex, which plays a crucial role in decision-making and impulse control. This method could potentially reduce alcohol cravings and improve self-control more directly than traditional therapies. Additionally, TBS is non-invasive and could provide faster results compared to medications that often require weeks to take effect.

What evidence suggests that this trial's treatments could be effective for Alcohol Use Disorder?

Research has shown that Theta Burst Stimulation (TBS) to the medial prefrontal cortex (mPFC) can help reduce drinking and decrease the brain's responsiveness to alcohol-related triggers. This effect may last up to three months after treatment. In this trial, some participants will receive real TBS to the mPFC, while others will receive sham TBS. Additionally, studies suggest that TBS to the dorsolateral prefrontal cortex (dlPFC) may also help decrease alcohol use. Participants will also be assigned to receive either real or sham TBS to the dlPFC. These findings indicate that TBS to either the mPFC or dlPFC could be promising treatments for Alcohol Use Disorder (AUD). The ongoing research aims to determine which brain area is more effective in reducing alcohol consumption. ^{2 3 4 6 7}

Who Is on the Research Team?

Merideth A Addicott, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults aged 21-75 with Alcohol Use Disorder (AUD), as indicated by an AUDIT score above 8. Participants must meet DSM-V criteria for AUD and cannot be at risk of pregnancy, nursing, or planning a pregnancy without reliable birth control. They should not have suicidal/homicidal thoughts, expect major medical changes soon, use psychoactive substances (except marijuana/nicotine) recently, or be on medications affecting alcohol intake/craving.

Inclusion Criteria

I am between 21 and 75 years old.

You have a score of 8 or higher on the AUDIT (Alcohol Use Disorders Identification Test), which means you are considered a medium or high-risk drinker.

Meets the DSM V criteria for having a current AUD, determined by DSM-V criteria, using the Structured Clinical Interview for DSM-V

Exclusion Criteria

I have had a serious brain injury that required hospitalization or caused me to lose consciousness for over 10 minutes.

You have used any drugs that affect your mind or mood, except for marijuana and nicotine, in the past month according to what you have told us.

Does not meet safety criteria for MRI and TMS

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 15 sessions of TMS (2x/day; 3x/week) over 5 weeks, targeting either the VMPFC or DLPFC.

5 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including alcohol consumption and craving.

4 months

3 monthly visits (in-person)

Extension

Optional continuation of monitoring and assessment for long-term outcomes.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Theta Burst Stimulation

Trial Overview

The study tests two transcranial magnetic stimulation (TMS) strategies to reduce alcohol consumption in individuals seeking treatment for AUD. It compares the effects of Real TBS versus Sham TBS applied to either the ventromedial prefrontal cortex (vmPFC) or dorsolateral prefrontal cortex (dlPFC) over four months on abstinence and reaction to alcohol cues.

How Is the Trial Designed?

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

Thirty sessions of real Theta Burst Stimulation (TBS) will be delivered to the left medial prefrontal cortex (mPFC)

Group II: Real TBS to the dlPFC Experimental Treatment 1 Intervention

Thirty sessions of real Theta Burst Stimulation (TBS) will be delivered to the left dorsolateral prefrontal cortex (dlPFC)

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

Thirty sessions of sham Theta Burst Stimulation (TBS) will be delivered to the left medial prefrontal cortex (mPFC)

Group IV: Sham TBS to the dlPFC Placebo Group 1 Intervention

Thirty sessions of sham Theta Burst Stimulation (TBS) will be delivered to the left dorsolateral prefrontal cortex (dlPFC)

Theta Burst Stimulation is already approved in United States for the following indications:

Approved in United States as Theta Burst Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

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]

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]

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

Repeated applications of Theta Burst stimulation (TBS) in rats showed complex effects on neuronal activity markers, with some markers increasing while others decreased, indicating that the response to TBS is not simply accumulative.

Specifically, while the expression of the vesicular glutamate transporter (VGLUT1) increased with stimulation, markers for inhibitory activity like GAD67 and calcium-binding proteins decreased, suggesting a nuanced interaction between excitatory and inhibitory neuronal responses to repeated TBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. Volz, LJ., Benali, A., Mix, A., et al.[2016]

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) 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]

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]

In a study involving 300 patients with treatment-resistant depression, accelerated bilateral theta burst stimulation (TBS) was found to be effective and safe, with a treatment response rate of 43.7% and a remission rate of 28.2%.

The study revealed no significant differences in efficacy between different TBS intensities or when compared to traditional unilateral 10 Hz rTMS, indicating that the accelerated TBS does not provide faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. Chen, L., Thomas, EHX., Kaewpijit, P., et al.[2022]

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