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

180 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Theta Burst Stimulation (TBS) for alcoholism?

Research shows that Theta Burst Stimulation (TBS), a type of transcranial magnetic stimulation, has been effective in reducing cravings for methamphetamine and cocaine, suggesting it might help with alcohol cravings too. TBS is also similar in effectiveness to other forms of brain stimulation used for depression, which supports its potential use for alcohol use disorder. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation, including its variant theta burst stimulation (TBS), has been shown to be generally safe and well-tolerated in studies for various conditions like depression and substance use disorders. Some participants may experience mild side effects like headaches, but serious adverse events are rare. ^{1 2 3 5 6}

How is Theta Burst Stimulation (TBS) different from other treatments for alcoholism?

Theta Burst Stimulation (TBS) is a unique treatment for alcoholism because it uses magnetic pulses to stimulate specific brain areas, is shorter in duration, and potentially more tolerable than traditional repetitive transcranial magnetic stimulation (rTMS). It has shown promise in reducing cravings in addiction disorders, although its full effects on alcohol use disorder are still being studied. ^{1 2 5 7 8}

Research Team

Merideth A Addicott, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

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]

References

1. 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]

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

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

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019]

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

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. [2016]

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022]