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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for alcohol use disorder (AUD) using deep repetitive transcranial magnetic stimulation (rTMS), which applies magnetic pulses to specific brain areas. Researchers aim for rTMS to reduce alcohol cravings and influence drinking behavior by targeting brain regions linked to memory and decision-making. The trial includes an active treatment group and a sham (inactive) group for comparison. Suitable participants have a moderate to severe alcohol use disorder, drink regularly, and have no other major health issues or psychiatric conditions. As an unphased trial, participants can contribute to groundbreaking research that could lead to new treatment options for AUD.

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 prior data suggests that this brain stimulation technique is safe for treating alcohol use disorder?

Research has shown that rTMS (repetitive transcranial magnetic stimulation) is generally safe when used according to current guidelines. In one study, participants with alcohol use disorder (AUD) who received rTMS reported few serious side effects. Most side effects were mild, such as headaches or discomfort on the scalp where the treatment was applied.

Safety reviews indicate that rTMS can be safely used in both healthy individuals and those with brain-related conditions, including AUD. So far, the treatment appears well-tolerated, with very few reports of serious adverse effects. Overall, rTMS is considered a safe option for those exploring new treatments for AUD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about rTMS (repetitive Transcranial Magnetic Stimulation) for alcoholism because it offers a novel approach compared to traditional treatments like counseling, medication, and support groups. Unlike these methods, rTMS uses magnetic fields to stimulate specific areas of the brain associated with addiction, potentially reducing cravings and relapse rates. Its non-invasive nature and the ability to target brain circuits directly make it a promising alternative that could enhance recovery outcomes for individuals struggling with alcoholism.

What evidence suggests that rTMS is effective for alcohol use disorder?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help reduce the urge to drink in people with alcohol use disorder (AUD). In this trial, participants will join either an active stimulation arm, receiving active rTMS, or a sham stimulation arm, receiving sham stimulation with a smaller coil within the rTMS device. Studies have also found that rTMS might lower the number of days people drink heavily. This treatment targets specific brain areas involved in memory and decision-making, which can be affected in those with AUD. Magnetic fields activate nerve cells in these regions. While promising evidence suggests it can reduce cravings, more research is needed to confirm its effect on actual drinking habits. ^{1 3 6 7 8}

Who Is on the Research Team?

Jonathan Wai

Principal Investigator

New York State Psychiatric Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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 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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006322321018266

Repetitive Transcranial Magnetic Stimulation in Alcohol ... Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8878126/

rTMS Reduces Craving and Alcohol Use in Patients with ... These findings suggest that rTMS might be an effective add-on in treating patients with AUD and warrant replication in future large-scale ...

3. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05940-z

Efficacy of repetitive transcranial magnetic stimulation (rTMS ... Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior ...

4. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(21)01826-6/fulltext

Repetitive Transcranial Magnetic Stimulation in Alcohol ... Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02691390

Deep Repetitive Transcranial Magnetic Stimulation for ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4202564/

Repetitive Transcranial Magnetic Stimulation (rTMS) in the ... Therefore, the purpose of this review is to critically evaluate the efficacy of TMS in the treatment of alcohol dependence and other substance abuse disorders.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9879417/

Safety Review for Clinical Application of Repetitive ... rTMS conforming to the current safety guidelines (Tables 3, 4, 5) can be applied safely to both healthy volunteers and patients with acquired brain diseases ...

8. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20240403

Assessment and Management of Concurrent Substance ... Clinical practice recommendations for the assessment and management of alcohol use during repetitive transcranial magnetic stimulation (rTMS) ...