Transcranial Magnetic Stimulation for Alcoholism

Overseen By Brett C Ginsburg, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center at San Antonio

Disqualifiers: Substance use disorder, Bipolar, Schizophrenia, Seizure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is testing a new treatment called IR-TMS (image-guided, robot navigated transcranial magnetic stimulation) to see if it can help people who drink too much alcohol to reduce the amount they drink. Participants will be placed into one of three groups, each receiving a slightly different version of this treatment. The study involves going through a few sessions of IR-TMS, having brain scans (MRI), providing blood and urine samples, and answering questions about their drinking and mental health. These activities are part of the study and aren't usually part of regular treatment for alcohol use. IR-TMS is different from regular treatments like therapy or medication because it uses magnetic fields to target specific parts of the brain. The goal is to see if this treatment can help reduce the urge to drink. There are other options, like sticking with therapy or medication, which are less intense but have been used for a longer time.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to understand how your medications might interact with the trial.

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. Studies have used TMS in various conditions, including alcohol dependence, without significant safety concerns. ^{1 2 3 4 5}

How is the treatment Image-guided, Robot Navigated Transcranial Magnetic Stimulation (TMS) for alcoholism different from other treatments?

This treatment is unique because it uses a non-invasive method to stimulate specific areas of the brain with magnetic pulses, guided by imaging techniques like MRI, to precisely target brain regions involved in alcohol cravings. Unlike other treatments, it offers a direct way to influence brain activity without medication, potentially reducing cravings and aiding in recovery. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Image-guided, Robot Navigated Transcranial Magnetic Stimulation (TMS) for alcoholism?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce alcohol cravings and intake in people with alcohol use disorder. Studies have found that targeting specific brain areas with rTMS can influence brain activity related to addiction, suggesting it may help in treating alcoholism. ^{1 2 4 10 11}

Research Team

Brett C Ginsburg, PhD

Principal Investigator

The University of Texas Health Science Center at San Antonio

Eligibility Criteria

This trial is for individuals struggling with Alcohol Use Disorder (AUD) who are seeking a new treatment option. Participants must be willing to undergo brain scans, provide samples, and answer questions about their drinking habits and mental health.

Inclusion Criteria

Two self-reported heavy drinking episodes (>4 drinks for men, >3 for women) or >13 drinks in the last 14 days (at screening)

I can attend all required study visits.

PEth >20 ng/mL (at baseline)

Exclusion Criteria

Current diagnosis of a moderate or severe substance use disorder (SUD; other than AUD, cannabis, or nicotine)

Inability to provide informed consent

I am not pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 4 IR-TMS treatments per day for up to 10 days, targeting specific brain regions

2 weeks

Daily visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including brain scans and biomarker analysis

6 months

Periodic visits for assessments

Treatment Details

Interventions

• Image-guided, Robot Navigated Transcranial Magnetic Stimulation (TMS)

Trial Overview The study tests IR-TMS, a non-invasive procedure using magnetic fields to target brain areas linked to addiction. It aims to reduce alcohol cravings by varying the treatment across three groups in multiple sessions alongside regular monitoring through MRI scans and sample collection.

Participant Groups

Group I: Orbitofrontal cortex (OFC) IR-TMS Active Control 1 Intervention

Stimulation will be delivered to either the OFC at a depth corrected intensity of 80-95 V/m, using a theta burst stimulation protocol which delivers 1,800 pulses/session. Sessions will be compressed and delivered up to 4 times per day, over the course of 2 weeks.

Group II: Left dorsolateral prefrontal cortex (L-DLPFC) IR-TMS Active Control 1 Intervention

Stimulation will be delivered to the L-DLPFC at a depth corrected intensity of 80-95 V/m, using a theta burst stimulation protocol which delivers 1,800 pulses/session. Sessions will be compressed and delivered up to 4 times per day, over the course of 2 weeks.

Group III: Dorsomedial prefrontal cortex (DMPFC) IR-TMS Active Control 1 Intervention

Stimulation will be delivered to either the DMPFC at a depth corrected intensity of 80-95 V/m, using a theta burst stimulation protocol which delivers 1,800 pulses/session. Sessions will be compressed and delivered up to 4 times per day, over the course of 2 weeks.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Wellcome Leap Inc.

Collaborator

Trials

2

Recruited

280+

Wellcome Leap Inc.

Industry Sponsor

Trials

1

Recruited

150+

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 study involving 51 patients with alcohol use disorder, deep repetitive transcranial magnetic stimulation (dTMS) significantly reduced the percentage of heavy drinking days compared to a sham treatment, indicating its potential efficacy as a treatment for alcohol addiction.

The treatment was associated with changes in brain connectivity, particularly in areas linked to addiction, suggesting that dTMS may work by altering neural circuits involved in alcohol use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices. Harel, M., Perini, I., Kämpe, R., 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) shows promise as a neuromodulation treatment for alcohol use disorder (AUD), particularly by targeting the salience network in the brain, which is linked to addiction and relapse.

Stimulation of specific brain areas, such as the anterior insula and dorsal anterior cingulate cortex, may enhance the effectiveness of rTMS in reducing relapse rates in individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Padula, CB., Tenekedjieva, LT., McCalley, DM., et al.[2022]

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 12 healthy male volunteers, acamprosate was found to increase the motor threshold, indicating a reduction in the excitability of the motor cortex compared to a placebo.

This hypoexcitability effect of acamprosate may be linked to subcortical mechanisms rather than direct changes in cortical inhibition or facilitation, suggesting a complex interaction in the brain's response to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acamprosate reduces motor cortex excitability determined by transcranial magnetic stimulation. Wohlfarth, K., Schneider, U., Haacker, T., et al.[2018]

Transcranial magnetic stimulation (TMS) is a non-invasive brain imaging technique that can causally link specific cortical areas to physiological responses, making it more precise than other imaging methods.

Navigated TMS has shown clinical effectiveness in mapping motor areas, assessing recovery after stroke, and treating conditions like depression, but further development of targeting and dosing protocols is needed for improved accuracy and reproducibility in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation. Ruohonen, J., Karhu, J.[2016]

Navigated transcranial magnetic stimulation (TMS) combined with MRI allows for precise mapping of brain functions by accurately correlating the position of the stimulating coil on the scalp with the underlying cortical anatomy.

This technique enhances the reliability of TMS for localizing cortical functions, making it a valuable tool for preoperative planning in patients with brain lesions near critical areas like the rolandic cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology. Krings, T., Chiappa, KH., Foltys, H., et al.[2019]

Stereotactic transcranial magnetic stimulation (TMS) was successfully used in two patients to map motor functions in the brain before surgery, showing it is a well-tolerated and noninvasive technique.

The TMS results closely matched those obtained from direct electrical cortical stimulation during surgery, with over 75% of TMS responses occurring within 1 cm of the stimulation site, indicating its accuracy for presurgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation. Krings, T., Buchbinder, BR., Butler, WE., et al.[2019]

Transcranial magnetic stimulation (TMS) can effectively generate functional brain maps by stimulating neurons and measuring responses in motor and sensory functions, allowing for detailed mapping of areas like the motor and visual cortex.

The developed registration system enhances the accuracy of TMS by providing real-time feedback for probe placement, which is crucial for applications in neuroanatomy research, surgical planning, and monitoring treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimentation with a transcranial magnetic stimulation system for functional brain mapping. Ettinger, GJ., Leventon, ME., Grimson, WE., et al.[2019]

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

Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices. [2022]

4. 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]

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

Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. [2022]

6. 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]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Acamprosate reduces motor cortex excitability determined by transcranial magnetic stimulation. [2018]

8. France pubmed.ncbi.nlm.nih.gov

Navigated transcranial magnetic stimulation. [2016]

9. Germany pubmed.ncbi.nlm.nih.gov

Introducing navigated transcranial magnetic stimulation as a refined brain mapping methodology. [2019]

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

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Experimentation with a transcranial magnetic stimulation system for functional brain mapping. [2019]