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

Trial Summary

What is the purpose of this trial?

This is a pilot randomized controlled trial (RCT) for Veteran participants with alcohol use disorder co-occurring with mild traumatic brain injury and/or post-traumatic stress disorder. The treatment intervention is repetitive Transcranial Magnetic Stimulation (rTMS) and the goal is to reduce alcohol craving with this treatment. The study will enroll 20 Veteran participants. Half of these participants will receive real rTMS and half of the participants will receive placebo rTMS. rTMS treatment will be provided over 10 sessions that will occur once every weekday for 2 weeks. Veteran participants will then complete follow-up phone calls to further evaluate alcohol craving and other symptoms.

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 data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for co-occurring Alcohol Use Disorder (AUD) and mild Traumatic Brain Injury (mTBI)?

Research shows that rTMS can help reduce symptoms in people with either AUD or mTBI when treated separately. For mTBI, rTMS has been found to alleviate headaches and improve mental focus, suggesting it might be effective for co-occurring conditions. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, with safety guidelines established and updated over the years. Common side effects can include headaches and sleep disturbances, but these are usually mild and temporary. Careful selection of protocols and patient screening can minimize risks, such as seizures, especially in individuals with traumatic brain injuries. ^{2 6 7 8 9}

How is the treatment rTMS unique for AUD and mTBI?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, potentially addressing overlapping symptoms of alcohol use disorder (AUD) and mild traumatic brain injury (mTBI) together. Unlike traditional treatments, rTMS can target the brain directly without the need for medication, making it a novel option for these co-occurring conditions. ^{4 5 8 9 10}

Research Team

Amy A Herrold, PhD BA

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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]

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 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]

References

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

Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. [2022]

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

Noninvasive brain stimulation for persistent postconcussion symptoms in mild traumatic brain injury. [2022]

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

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. [2022]

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

Repetitive transcranial magnetic stimulation-associated neurobehavioral gains during coma recovery. [2016]

5. India pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders. [2020]

6. Netherlands 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. [2019]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

8. United States 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. [2022]

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

Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. [2019]