TMS for Alcohol Use Disorder

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Palo Alto Health Care System

Must not be taking: Benzodiazepines, Neuroleptics

Disqualifiers: Substance abuse, Seizure disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that your current medication regimen remains stable throughout the study. However, you must stop taking any medications that increase seizure risk at least two weeks before treatment.

What data supports the effectiveness of this treatment for alcohol use disorder?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) may help reduce alcohol cravings and intake in people with alcohol use disorder. Some studies have shown that rTMS can influence brain activity related to addiction, potentially making it a promising treatment option. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Research suggests that rTMS is generally safe for humans, including those with substance use disorders, although more detailed studies are needed to fully understand its safety in people with varying levels of substance use. ^{4 5 6 7 8}

How does the treatment TMS differ from other treatments for alcohol use disorder?

Transcranial Magnetic Stimulation (TMS) is unique because it is a non-invasive brain stimulation technique that targets specific brain areas to reduce alcohol cravings and use, unlike traditional treatments that often involve medication or therapy. It uses magnetic fields to stimulate nerve cells in the brain, particularly the dorsolateral prefrontal cortex, which is associated with addiction and cravings. ^{1 2 4 7 9}

What is the purpose of this trial?

Alcohol Use Disorders are currently positioned as the third leading cause of preventable death in the United States, constituting a humanitarian crisis with substantial financial burden on society and medical facilities. While several pharmacological interventions exist, 60% of individuals who seek these treatments relapse to alcohol within 6 months. These high relapse rates are due in part to elevated brain response to alcohol cues in the environment. This study seeks to evaluate the efficacy of one session of functional Magnetic Resonance Imaging (fMRI) guided transcranial magnetic stimulation (TMS) as a strategy to reduce brain reactivity to alcohol cues.

Research Team

Daniel McCalley, PhD

Principal Investigator

Palo Alto VA Health Care System

Eligibility Criteria

This trial is for individuals struggling with Alcohol Use Disorder. Participants should have a history of alcoholism and be seeking treatment. Specific details about inclusion and exclusion criteria are not provided, but typically these would outline health conditions, age range, and other factors relevant to the study.

Inclusion Criteria

Able to read, understand and voluntarily sign Informed Consent prior to participating in any study-specific procedures or assessments

My current medication will not change throughout the study.

Current DSM-5 diagnosis of moderate to severe AUD (≥4 diagnostic symptoms)

Exclusion Criteria

General medical condition, disease or neurological disorder that interferes with the assessments or participation

Severe impediment to vision, hearing and/or hand movement, likely to interfere with the ability to follow study protocols

I have had a brain injury with more than 10 minutes of unconsciousness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one session of fMRI-guided TMS targeting peak functional connectivity to the ventral striatum

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in brain reactivity to alcohol cues post-TMS

1 day

1 visit (in-person)

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study is testing the effectiveness of transcranial magnetic stimulation (TMS), guided by brain imaging (fMRI), in reducing the brain's response to alcohol-related cues which can lead to relapse in people with Alcohol Use Disorder.

Participant Groups

Group I: Active fMRI-guided TMS Experimental Treatment 1 Intervention

Group II: Sham fMRI-guided TMS Placebo Group 1 Intervention

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

VA Palo Alto Health Care System

Lead Sponsor

Trials

97

Recruited

58,500+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

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 pilot study involving 14 patients with alcohol use disorder (AUD), deep repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex led to a significant reduction in dopamine transporter (DAT) availability and alcohol intake after four weeks of treatment.

The results suggest that rTMS may modulate dopaminergic activity, indicating its potential efficacy as a therapeutic intervention for reducing alcohol consumption in AUD patients, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex in Alcohol Use Disorder Patients: Effects on Dopamine Transporter Availability and Alcohol Intake. Addolorato, G., Antonelli, M., Cocciolillo, F., et al.[2018]

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]

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising and safe treatment for alcohol use disorders (AUDs), potentially addressing the limited therapeutic options currently available.

rTMS may work by altering neurocircuitries related to alcohol addiction, with evidence from visual imaging studies and clinical pilot studies showing its effects on reducing alcohol craving and intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation: Re-wiring the alcoholic human brain. Diana, M., Bolloni, C., Antonelli, M., et al.[2020]

Repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe and feasible for patients with neuropsychiatric disorders who also have a history of substance use, based on a review of 274 articles.

However, the impact of different levels of substance use on the safety and efficacy of rTMS remains unclear, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. Tang, VM., Ibrahim, C., Rodak, T., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in reducing cravings for tobacco, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC), based on a review of eight studies.

Repeated sessions of high-frequency rTMS over the DLPFC may be particularly beneficial for decreasing smoking and alcohol consumption, suggesting that rTMS could be a promising treatment option for drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. Barr, MS., Farzan, F., Wing, VC., et al.[2019]

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]

In a study involving 30 recently detoxified patients with alcohol use disorder, high-frequency rTMS applied over the right dorsolateral prefrontal cortex significantly reduced alcohol craving and use during the first three months after treatment compared to a sham treatment.

However, the effects of rTMS on craving and alcohol use diminished by the 12-month follow-up, indicating that while rTMS may be a beneficial short-term add-on treatment for alcohol use disorder, its long-term efficacy needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS Reduces Craving and Alcohol Use in Patients with Alcohol Use Disorder: Results of a Randomized, Sham-Controlled Clinical Trial. Belgers, M., Van Eijndhoven, P., Markus, W., et al.[2022]

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

Deep Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex in Alcohol Use Disorder Patients: Effects on Dopamine Transporter Availability and Alcohol Intake. [2018]

4. 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]

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

Repetitive transcranial magnetic stimulation: Re-wiring the alcoholic human brain. [2020]

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

Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. [2023]

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

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

rTMS Reduces Craving and Alcohol Use in Patients with Alcohol Use Disorder: Results of a Randomized, Sham-Controlled Clinical Trial. [2022]