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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Image-guided, Robot Navigated Transcranial Magnetic Stimulation (IR-TMS), a non-invasive brain stimulation technique, to help reduce alcohol intake. Participants will be divided into three groups, each receiving a slightly different version of the treatment targeting specific brain areas. Suitable candidates have experienced multiple recent heavy drinking episodes and are diagnosed with moderate to severe alcohol use disorder. The study requires participants to attend several sessions and complete assessments involving brain scans and surveys about drinking habits. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment options for alcohol use disorder.

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.

What prior data suggests that this IR-TMS technique is safe for treating alcoholism?

Research has shown that transcranial magnetic stimulation (TMS) treatments, like those in this trial, have generally been well-tolerated. Specifically, treatments targeting the orbitofrontal cortex, left dorsolateral prefrontal cortex, and dorsomedial prefrontal cortex have proven safe.

For orbitofrontal cortex TMS, safety guidelines and expert advice confirm its safety when used correctly. No serious side effects have been widely reported in healthy individuals or patients.

The left dorsolateral prefrontal cortex TMS has been studied for aiding smoking cessation and other conditions, with participants typically experiencing only minor side effects. The most common side effects include mild headaches or slight discomfort at the stimulation site, which usually resolve on their own.

Similarly, dorsomedial prefrontal cortex TMS has been tested for safety in various mental health conditions. Studies have shown it to be safe, with no major safety concerns reported.

Overall, TMS treatments like these have been used safely in various conditions, providing reassurance about their safety for this trial. Prospective participants should consult a doctor to understand the benefits and any potential risks based on personal health. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using transcranial magnetic stimulation (TMS) for alcoholism because it offers a non-invasive, brain-focused approach that differs from traditional treatments like medication and behavioral therapy. Unlike standard options, TMS targets specific brain areas such as the orbitofrontal cortex, left dorsolateral prefrontal cortex, and dorsomedial prefrontal cortex, delivering focused magnetic pulses to potentially alter brain activity patterns associated with addiction. This method uses a unique image-guided, robot-navigated system to ensure precision and can deliver results more rapidly, with sessions compressed into a span of just two weeks. Researchers hope this could lead to more effective and quicker interventions for people struggling with alcohol use disorder.

What evidence suggests that this trial's treatments could be effective for reducing alcohol consumption?

This trial will compare the effects of transcranial magnetic stimulation (TMS) on different brain regions to help manage alcohol consumption. Studies have shown that TMS can reduce the desire to drink and the amount of alcohol consumed by people with alcohol use disorder. In this trial, participants will receive TMS targeting the orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (L-DLPFC), or dorsomedial prefrontal cortex (DMPFC). Research suggests that using TMS on these specific brain areas, involved in decision-making and cravings, may lessen the urge to drink. Past patients demonstrated that repetitive TMS on another brain area can help people quit smoking and might also help with alcohol use. Additionally, stimulating a different brain region has been linked to improvements in other mental health conditions, indicating possible benefits for alcohol use. These findings suggest that TMS could be a promising tool to help manage alcohol consumption by focusing on brain areas related to cravings and decision-making. ^{1 2 3 4 6}

Who Is on the Research Team?

Brett C Ginsburg, PhD

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

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)

PEth >20 ng/mL (at baseline)

Fluent in English

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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) 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]

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]

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]

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]

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]

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]

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]

Citations

1. ctv.veeva.com ctv.veeva.com/study/image-guided-robot-navigated-transcranial-magnetic-stimulation-tms-for-alcohol-use-disorder-aud

Image-guided, Robot Navigated Transcranial Magnetic ... The study involves going through a few sessions of IR-TMS, having brain scans (MRI), providing blood and urine samples, and answering questions ...

2. withpower.com withpower.com/trial/phase-alcohol-use-disorders-aud-9-2024-7b9cc

Transcranial Magnetic Stimulation for Alcoholism Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce alcohol cravings and intake in people with alcohol use disorder. Studies have ...

3. reporter.nih.gov reporter.nih.gov/project-details/11178406

Developing Functional Connectivity-Guided TMS for Alcohol ... Evidence from neuroimaging studies of AUD patients has shown that elevated cortico-striatal activity in response to alcohol cues predicts relapse. Thus, there ...

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

rTMS Reduces Craving and Alcohol Use in Patients with ... This small-scale randomized controlled trial showed the efficacy of high-frequency rTMS over the right dlPFC diminished alcohol craving and use in recently ...

5. mdpi.com mdpi.com/2076-3425/12/1/48

Repetitive Transcranial Magnetic Stimulation for Comorbid ... Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method that has demonstrated antidepressant effects.

6. researchgate.net researchgate.net/publication/328832322_A_Comprehensive_Review_of_Dorsomedial_Prefrontal_Cortex_rTMS_Utilizing_a_Double_Cone_Coil_DORSOMEDIAL_PREFRONTAL_CORTEX_DCC_rTMS

DORSOMEDIAL PREFRONTAL CORTEX DCC rTMS Results DCC stimulation over the dmPFC has been proven to be safe and feasible in various neuropsychiatric disorders and in healthy subjects. Clinical results ...