Transcranial Magnetic Stimulation for Alcoholism

(TMS Trial)

Overseen By Michiyah Kimber

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must not be taking: Psychoactive substances, Seizure threshold

Disqualifiers: Substance use disorder, Psychiatric disorder, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4 days

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants do not take medications known to affect alcohol intake or craving, and those that lower the seizure threshold. If you are on such medications, you may need to stop taking them to participate.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for alcoholism?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce cravings in people with alcohol dependence by targeting specific brain areas. It is also approved for treating depression, suggesting it can influence brain activity in beneficial ways. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS) is generally considered safe for humans and is already approved by the Food and Drug Administration (FDA) for treating depression. It has been used in studies involving various addictions, including alcohol, with no major safety concerns reported. ^{2 4 5 6 7}

How does transcranial magnetic stimulation (TMS) differ from other treatments for alcoholism?

Transcranial magnetic stimulation (TMS) is unique because it is a noninvasive treatment that uses magnetic fields to stimulate specific areas of the brain, unlike traditional treatments that often involve medication or therapy. It is particularly novel for alcoholism as it targets brain circuits involved in addiction, offering a new approach to reduce alcohol cravings and potentially improve treatment outcomes. ^{1 2 3 5 8}

What is the purpose of this trial?

Alcohol use disorder (AUD) is a complex chronic brain disease characterized by compulsive alcohol use, loss of control over drinking, and negative emotional states. Extensive research has identified the general neural circuitry underlying AUD. There is an exciting opportunity to intervene in AUD using neuromodulation. Transcranial magnetic stimulation (TMS) offers a non-invasive method to modulate brain activity, making it a promising tool for investigating, modulating, and potentially treating AUD. However, the precise effects of TMS on neural circuits involved in AUD and the mechanisms underlying these effects must first be understood. Magnetoencephalography (MEG) is a neuroimaging method that provides direct measurement of brain activity within neural circuits with high temporal resolution. Critically, MEG can measure brain activity in a wide range of frequencies that are consistent with those targeted by TMS. The goal of this proposal is therefore to collect preliminary and feasibility data to support a future NIH grant application that would use MEG to investigate TMS effects in individuals with AUD (iAUD).

Research Team

Merideth A Addicott, PhD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for individuals with Alcohol Use Disorder (AUD). To join, participants must have a certain score on the DSM-5 and AUDIT indicating they either consume little to no alcohol or are heavy alcohol consumers. Those who don't meet these specific criteria cannot participate.

Inclusion Criteria

* Diagnostic and Statistical Manual of Mental Disorders (DSM-5) score for AUD = 0

* Alcohol Use Disorders Identification Test (AUDIT) score ≤ 7

* Is not a heavy alcohol consumer

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TMS pulse sequences and undergo MEG scans to measure brain activity

4 days

4 visits (in-person) for Four Day option; 2 visits (in-person) for Two Day option

Follow-up

Participants are monitored for adverse events potentially related to TMS

1 year

Treatment Details

Interventions

• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study tests how Transcranial Magnetic Stimulation (TMS) affects brain activity in people with AUD using Magnetoencephalography (MEG). Different frequencies of TMS, including 10 Hz and 1 Hz, as well as active and sham intermittent Theta Burst Stimulation (iTBS), are being compared.

Participant Groups

Group I: Two Day - Option 2 Experimental Treatment 2 Interventions

Participants will receive sham iTBS then active iTBS.

Group II: Two Day - Option 1 Experimental Treatment 2 Interventions

Participants will receive active iTBS then sham iTBS.

Group III: Four Day - Option 2 Experimental Treatment 4 Interventions

Participants will receive sham iTBS, active iTBS, 1 Hz, 10 Hz.

Group IV: Four Day - Option 1 Experimental Treatment 4 Interventions

Participants will receive active iTBS, sham iTBS, 10 Hz, 1 Hz.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

High-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right dorsolateral pre-frontal cortex significantly reduced alcohol craving in 45 patients with alcohol dependence, demonstrating its potential as an effective treatment strategy.

The study showed a moderate effect size for the anticraving effects of rTMS, suggesting that it could be combined with other medications to further reduce cravings and prevent relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study. Mishra, BR., Nizamie, SH., Das, B., et al.[2022]

Transcranial magnetic stimulation (TMS) is emerging as a promising noninvasive treatment for substance dependence, potentially filling a gap in addiction therapies, as it is already FDA-approved for depression.

Repetitive TMS (rTMS) has shown potential in altering behavior and brain activity related to addiction, and future studies may benefit from combining rTMS with medications and cognitive behavioral therapies to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. Hanlon, CA., Dowdle, LT., Henderson, JS.[2019]

In a chronic alcoholic patient with slight brain atrophy, transcranial magnetic stimulation (TMS) revealed an increased resting threshold and a dominance of D waves, indicating direct stimulation of corticospinal neurons, while I waves were unclear or absent.

The absence of clear I waves suggests impairment in the interneuronal circuitry due to brain damage from chronic alcohol abuse, highlighting how alcohol can affect motor pathways in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy. Di Lazzaro, V., Oliviero, A., Pilato, F., et al.[2019]

In a study involving 60 male inpatients with alcohol dependence, repetitive transcranial magnetic stimulation (rTMS) was administered over ten daily sessions, targeting the left dorsolateral prefrontal cortex (DLPFC).

The results showed no significant reduction in alcohol craving scores immediately after treatment or two weeks later, indicating that rTMS may not be effective for reducing cravings in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sham-controlled trial of repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex and its effects on craving in patients with alcohol dependence. Raikwar, S., Divinakumar, KJ., Prakash, J., et al.[2022]

In a study involving 80 detoxified patients with alcohol use disorder, 10 sessions of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) did not significantly increase the number of abstinent days over a 6-month follow-up compared to a sham treatment.

HF-rTMS also showed no impact on alcohol craving levels, indicating that this treatment may not be effective as an add-on therapy for reducing alcohol use or cravings in patients with alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 10 add-on HF-rTMS treatment sessions on alcohol use and craving among detoxified inpatients with alcohol use disorder: a randomized sham-controlled clinical trial. Hoven, M., Schluter, RS., Schellekens, AF., et al.[2023]

Transcranial magnetic stimulation (TMS) has been explored in 19 studies involving 316 adults for its potential to reduce drug cravings and use, particularly targeting the dorsolateral prefrontal cortex with high-frequency pulses.

While some studies showed promising results, such as decreased smoking and cocaine use, the treatment is still experimental, and the exact mechanisms and optimal parameters for rTMS in addiction treatment remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of substance addiction. Gorelick, DA., Zangen, A., George, MS.[2022]

Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral pre-frontal cortex significantly reduces craving for substances in patients with dependence, with a strong effect size (Hedges' g = -0.62) based on a meta-analysis of 26 randomized controlled trials involving 748 participants.

In addition to reducing cravings, rTMS also effectively decreases substance consumption, particularly when using excitatory stimulation protocols, indicating its potential as a therapeutic intervention for substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Zhang, JJQ., Fong, KNK., Ouyang, RG., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study. [2022]

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

Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. [2019]

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

Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy. [2019]

4. India pubmed.ncbi.nlm.nih.gov

A sham-controlled trial of repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex and its effects on craving in patients with alcohol dependence. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effects of 10 add-on HF-rTMS treatment sessions on alcohol use and craving among detoxified inpatients with alcohol use disorder: a randomized sham-controlled clinical trial. [2023]

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

Transcranial magnetic stimulation in the treatment of substance addiction. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. [2020]

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

Transcranial magnetotherapy in the complex treatment of affective disorders in patients with alcoholism. [2021]