rTMS for AUD+mTBI

(TMS_AUD+mTBI Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Anti-epileptics, Tricyclics, Antipsychotics, others

Disqualifiers: Severe TBI, Schizophrenia, Bipolar, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called repetitive Transcranial Magnetic Stimulation (rTMS) to reduce alcohol cravings in Veterans with mild traumatic brain injury or post-traumatic stress disorder. Participants will receive either the real rTMS treatment or a placebo version over 10 sessions, conducted once every weekday for two weeks. The trial seeks Veterans who speak English, meet specific criteria for alcohol use disorder, and have mild traumatic brain injury or PTSD. Veterans dealing with these issues and interested in exploring new treatment options might find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including anti-epileptic drugs, tricyclic anti-depressants, antipsychotic agents, and any anti-craving or addiction medications like naltrexone or bupropion. If you are currently using opiates, cocaine, amphetamines, barbiturates, benzodiazepines, or have marijuana dependence, you would also need to stop.

What prior data suggests that rTMS is safe for treating alcohol use disorder with mild traumatic brain injury?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe. rTMS uses magnetic fields to stimulate brain cells, potentially aiding certain mental health issues.

Previous studies have examined rTMS for conditions like alcohol use disorder, mild traumatic brain injury, and post-traumatic stress disorder. These studies found rTMS safe, even for individuals with multiple head injuries. Participants reported few side effects, usually mild, such as headaches or slight discomfort at the magnet site.

The fact that rTMS has been studied for various conditions and is being tested in this trial suggests it is safe enough to explore further. However, individual experiences can vary. For personalized information, discussing concerns with the study team is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcohol use disorder?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive approach to treating Alcohol Use Disorder (AUD) with mild Traumatic Brain Injury (mTBI), unlike traditional treatments which often include medications and behavioral therapies. Researchers are excited about rTMS because it uses magnetic fields to stimulate nerve cells in the brain, which could potentially target the underlying neural pathways involved in AUD and mTBI more directly. This method has the potential to provide therapeutic benefits without the side effects associated with medications, and it could offer a new solution for those who haven't found relief with existing treatments.

What evidence suggests that rTMS might be an effective treatment for alcohol use disorder with mild traumatic brain injury?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) can help reduce alcohol cravings. One study found that combining high-frequency rTMS with cognitive-behavioral therapy (CBT) effectively prevented relapse in individuals with alcohol dependence. In this trial, participants will receive either active rTMS or placebo rTMS. For veterans with mild traumatic brain injury (mTBI), research indicates that rTMS works well, even if they also experience symptoms like PTSD. This treatment targets specific brain areas to improve function and reduce symptoms. Overall, rTMS has shown promise in helping with conditions like alcohol use disorder (AUD), particularly when other issues like mTBI are present. ^{1 2 3 4 6}

Who Is on the Research Team?

Amy A Herrold, PhD BA

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Are You a Good Fit for This Trial?

This trial is for English-speaking Veterans aged 22-65 with alcohol use disorder (AUD) and mild traumatic brain injury or PTSD. They must pass an MRI safety screening, have specific AUDIT-C scores, and not be in severe alcohol withdrawal. Exclusions include severe TBI, psychotic disorders, seizure history, certain medication use, substance dependence other than alcohol, recent mild TBI or surgery involving the heart/brain vessels.

Inclusion Criteria

Criterion: Military veterans

I am between 22 and 65 years old.

Your CIWA-Ar score is 10 or higher.

Exclusion Criteria

You have had a moderate to severe traumatic brain injury in the past.

You have talked about wanting to hurt yourself or have tried to hurt yourself in the past 6 months.

You have been diagnosed with schizophrenia or bipolar disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive 10 sessions of rTMS treatment, occurring once daily on weekdays over two weeks

2 weeks

10 visits (in-person)

Follow-up

Participants complete follow-up phone interviews to assess alcohol craving, mTBI symptoms, and PTSD symptoms

1 month

3 visits (phone)

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests repetitive Transcranial Magnetic Stimulation (rTMS) to reduce alcohol cravings in Veterans with AUD plus mTBI/PTSD. It's a randomized controlled trial where half receive real rTMS and half get placebo over two weeks (10 sessions). Follow-up calls assess craving levels post-treatment.

How Is the Trial Designed?

Group I: active Active Control 1 Intervention

active rTMS

Group II: placebo Placebo Group 1 Intervention

placebo rTMS

Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

In a study involving 7 participants with disordered consciousness after severe traumatic brain injury, repetitive transcranial magnetic stimulation (rTMS) was found to have a relatively safe profile, with only 75 mild nonserious adverse events and 1 serious adverse event (a seizure).

Despite the potential for seizure induction, the study suggests that rTMS can be safely administered to this vulnerable population, indicating that future research could include a broader range of patients who were previously excluded due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury. Kletzel, SL., Aaronson, AL., Guernon, A., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) can be safely administered to individuals with traumatic brain injury (TBI) when following specific guidelines, minimizing risks such as seizures.

In a case study of a 48-year-old man with severe TBI, rTMS treatment for post-TBI depression over 6 weeks led to a 49% reduction in depression symptoms, demonstrating its potential efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury. Nielson, DM., McKnight, CA., Patel, RN., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) was found to be safe for a patient with an implanted subdural cortical electrode, showing no serious adverse effects during treatment.

Ex-vivo experiments indicated that rTMS caused only a slight increase in coil temperature and no displacement of the electrodes, suggesting that rTMS can be safely applied in clinical settings for patients with such implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of repetitive transcranial magnetic stimulation in patients with implanted cortical electrodes. An ex-vivo study and report of a case. Phielipp, NM., Saha, U., Sankar, T., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is safe and well-tolerated in patients with persistent postconcussive symptoms (PCS) following mild traumatic brain injury (mTBI), with 12 out of 15 participants completing the treatment protocol.

The treatment resulted in a significant reduction in PCS severity, with an average decline of 14.6 points on the PCS Scale, and increased brain activation in the DLPFC during cognitive tasks, suggesting rTMS may effectively alleviate symptoms associated with mTBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation for persistent postconcussion symptoms in mild traumatic brain injury. Koski, L., Kolivakis, T., Yu, C., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduced headache intensity in veterans with mild traumatic brain injury (MTBI), with a 56.3% reduction in the REAL group compared to 15.4% in the SHAM group after one week.

The treatment was clinically feasible and effective, with 58.3% of the REAL group experiencing at least a 50% reduction in headache intensity, and a significant decrease in overall headache-related disability observed at the four-week assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. Leung, A., Shukla, S., Fallah, A., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Repetitive transcranial magnetic stimulation (rTMS) at the left prefrontal cortex significantly reduced headache intensity in veterans with persistent mild traumatic brain injury-related headaches (MTBI-HA), with a 25.3% reduction at one week and 23.0% at four weeks post-treatment compared to a sham group.

The rTMS treatment also led to a notable improvement in depressive symptoms, as measured by the Hamilton Rating Scale for Depression, indicating potential mood-enhancing benefits alongside headache relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. Leung, A., Metzger-Smith, V., He, Y., et al.[2022]

In a safety and efficacy study involving a 26-year-old man with severe traumatic brain injury (TBI), a 6-week rTMS protocol showed no adverse events, indicating it is a safe treatment option for individuals in a minimally conscious state.

The rTMS treatment was associated with a trend toward significant neurobehavioral improvements and enhanced neural conduction, suggesting its potential to facilitate recovery in patients with severe TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. Louise-Bender Pape, T., Rosenow, J., Lewis, G., et al.[2016]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40550124/

Protocol for a Pilot Randomized Controlled Trial This study aims to (1) test the preliminary efficacy of high-frequency rTMS provided to a customized neural target to treat functional disability among ...

2. researchprotocols.org researchprotocols.org/2025/1/e64909

A Customized Neural Transcranial Magnetic Stimulation ... Both our research and that of others show that co-occurring AUD and mTBI (AUD+mTBI) may exacerbate brain impairment, exacerbate symptoms (eg, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12235201/

A Customized Neural Transcranial Magnetic Stimulation ... Both our research and that of others show that co-occurring AUD and mTBI (AUD+mTBI) may exacerbate brain impairment, exacerbate symptoms (eg, alcohol craving ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03910686

Efficacy of Repetitive Transcranial Magnetic Stimulation ... In order to test whether combined therapy of high frequency rTMS (hf-rTMS) with CBT is better for preventing from relapse of alcohol dependence, we recruit ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S109471592201399X

Repetitive Transcranial Magnetic Stimulation for ... Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness.

6. journals.lww.com journals.lww.com/nrronline/fulltext/2014/09190/transcranial_magnetic_stimulation__potential.4.aspx

Transcranial magnetic stimulation: potential treatment for... Alcohol use disorder (AUD), mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD) share symptoms (Pape et al., 2013) and neuropathology.