rTMS for Alcoholism

(MAGNA Trial)

Overseen By Jonathan Wai, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: New York State Psychiatric Institute

Must not be taking: Sedative-hypnotics, Opiates, Anticonvulsants, others

Disqualifiers: Substance use disorder, Psychiatric illness, Seizures, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

44 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to investigate a treatment approach for alcohol use disorder (AUD) using a novel form of brain stimulation called deep repetitive transcranial magnetic stimulation (rTMS). The investigators will be targeting frontal regions of the brain that are important for memory and decision making. These brain regions have been shown to be impaired in patients with AUD. Previous studies have mostly used rTMS to a different frontal brain region that is not as deep. These studies have shown that rTMS can reduce craving for alcohol, but there is a lack of research showing that rTMS impacts alcohol consumption.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking certain psychotropic medications that affect brain activity or increase seizure risk. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment rTMS for alcoholism?

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

Is rTMS safe for treating alcoholism?

Repetitive Transcranial Magnetic Stimulation (rTMS) is generally considered safe for humans, as it is a non-invasive technique used in various studies for treating addiction, including alcohol dependence. While more research is needed, current studies suggest it can be safely applied to the brain to potentially reduce cravings and alcohol intake. ^{1 2 6 7 8}

How does rTMS treatment for alcoholism differ from other treatments?

rTMS (Repetitive Transcranial Magnetic Stimulation) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, such as the dorsolateral prefrontal cortex, which may help reduce alcohol cravings and intake. Unlike traditional medications, rTMS directly targets brain circuits involved in addiction, offering a novel approach for treating alcohol use disorder. ^{2 3 6 9 10}

Research Team

Jonathan Wai

Principal Investigator

New York State Psychiatric Institute

Eligibility Criteria

This trial is for adults aged 22-55 with moderate to severe alcohol use disorder who drink at least once a week. They must be medically healthy, without major illnesses or psychiatric conditions that could affect the study, not currently pregnant, and have no history of seizures or family epilepsy.

Inclusion Criteria

I am healthy with no history of major illnesses like heart disease or seizures.

You have a serious problem with drinking alcohol, as defined by the DSM-5.

I drink about 2 alcoholic drinks in an hour at least once a week.

Exclusion Criteria

You have a mental health condition, like major depression, that would make it difficult for you to take part in the study.

I do not use drugs other than alcohol or nicotine, especially no sedatives or opiates.

My family has a history of epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Detoxification

Participants undergo a brief detoxification period before starting rTMS treatment

1 week

Treatment

Participants receive 3 weeks of rTMS while in the research unit, including decision-making experiments and MRI scans

3 weeks

Daily sessions (inpatient)

Follow-up

Participants meet with a study physician for assessments of alcohol use and medical management sessions

6 weeks

Weekly visits (in-person)

Treatment Details

Interventions

• rTMS

Trial Overview The study tests deep rTMS brain stimulation on frontal regions involved in memory and decision-making in patients with alcohol use disorder. It aims to see if this can reduce alcohol craving and consumption compared to a sham treatment.

Participant Groups

Group I: Active Stimulation Experimental Treatment 2 Interventions

Participants will be receiving active rTMS.

Group II: Sham Stimulation Placebo Group 2 Interventions

Participants will be receiving sham stimulation with a smaller coil housed within the rTMS device.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

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]

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]

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]

In a study involving 26 recently detoxified alcohol-dependent patients, 15 sessions of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) significantly reduced general alcohol craving, indicating its potential efficacy as a treatment.

However, HF-rTMS did not change cue-induced alcohol craving or the underlying craving neurocircuit, suggesting that while it may help with overall craving, it does not directly affect responses to alcohol-related cues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients. Herremans, SC., Van Schuerbeek, P., De Raedt, R., et al.[2018]

In a study involving 22 alcohol-dependent patients and 22 healthy controls, it was found that patients had lower baseline grey matter volume (GMV) in various brain areas compared to controls, indicating potential brain structure differences related to addiction.

The study revealed that while 15 sessions of accelerated high-frequency rTMS did not significantly change GMV in alcohol-dependent patients, lower baseline GMV was associated with a higher risk of relapse, suggesting that brain structure may be a predictor of relapse in alcohol addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated repetitive transcranial magnetic stimulation does not influence grey matter volumes in regions related to alcohol relapse: An open-label exploratory study. Wu, GR., Baeken, C., Van Schuerbeek, P., et al.[2018]

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]

The study found that alcohol dependent patients (ADPs) exhibited higher connectivity in both the cognitive control network and the motivational network compared to healthy controls, indicating a potential imbalance in these systems.

Repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex significantly increased connectivity within the cognitive control network in ADPs, suggesting that rTMS may enhance cognitive control and help reduce alcohol-related problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resting state connectivity in alcohol dependent patients and the effect of repetitive transcranial magnetic stimulation. Jansen, JM., van Wingen, G., van den Brink, W., et al.[2016]

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 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]

In a study involving 20 patients with alcohol dependence, both right and left dorsolateral prefrontal cortex (DLPFC) rTMS significantly reduced alcohol craving scores, indicating its efficacy in treating cravings.

Despite the effectiveness of rTMS in reducing cravings, there was no significant difference in anticraving efficacy between the right and left DLPFC stimulation, suggesting that either side can be used effectively for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of anticraving efficacy of right and left repetitive transcranial magnetic stimulation in alcohol dependence: a randomized double-blind study. Mishra, BR., Praharaj, SK., Katshu, MZ., 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. 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]

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

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

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

The Impact of Accelerated Right Prefrontal High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Cue-Reactivity: An fMRI Study on Craving in Recently Detoxified Alcohol-Dependent Patients. [2018]

5. Ireland pubmed.ncbi.nlm.nih.gov

Accelerated repetitive transcranial magnetic stimulation does not influence grey matter volumes in regions related to alcohol relapse: An open-label exploratory study. [2018]

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

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Resting state connectivity in alcohol dependent patients and the effect of repetitive transcranial magnetic stimulation. [2016]

8. 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]

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]

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

Comparison of anticraving efficacy of right and left repetitive transcranial magnetic stimulation in alcohol dependence: a randomized double-blind study. [2022]