Magnetic Brain Stimulation for TBI and Alcoholism

(rTMS-TARGET-ID Trial)

Overseen By Ibuola Kale

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Benzodiazepines, Opiates, Cocaine, Amphetamines

Disqualifiers: Moderate-severe TBI, Neurodegenerative diseases, Psychotic disorders, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for Veterans with both mild traumatic brain injury (mTBI) and alcohol use disorder (AUD). The focus is on repetitive transcranial magnetic stimulation (rTMS), a non-invasive method that uses magnetic fields to stimulate specific brain areas. Participants will be divided into groups receiving different types of brain stimulation to determine which target is most effective. The trial seeks Veterans who meet specific diagnostic criteria for AUD and mTBI but have not experienced more severe brain injuries or certain other conditions. The goal is to find the best way to help Veterans improve their daily functioning and mental health. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in care.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used benzodiazepines, opiates, cocaine, or amphetamines in the past 30 days.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used benzodiazepines, opiates, cocaine, or amphetamines in the past 30 days.

What prior data suggests that this magnetic brain stimulation technique is safe for treating TBI and alcoholism?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for people with traumatic brain injuries (TBI). Studies have found that when administered according to specific guidelines, the treatment is well-tolerated and safe. Common side effects might include mild headaches or scalp discomfort, but these usually resolve quickly.

rTMS is also used to treat depression and has FDA approval for that purpose, indicating a reasonable safety profile. However, individual experiences may vary, so discussing any concerns with a healthcare provider before joining a clinical trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about magnetic brain stimulation for treating traumatic brain injury (TBI) and alcoholism because it offers a novel approach that could enhance brain recovery and reduce addiction. Unlike traditional treatments that might involve medication or psychotherapy, this technique uses targeted magnetic pulses to stimulate specific brain areas, potentially improving function and reducing cravings. The use of custom neural targets, identified via neuroimaging, allows for precision in stimulation, which could lead to more effective outcomes compared to more generalized treatments. Additionally, the non-invasive nature of magnetic brain stimulation means it could be a safer alternative with fewer side effects.

What evidence suggests that this trial's treatments could be effective for AUD and mTBI?

Research shows that repetitive transcranial magnetic stimulation (rTMS) could help treat alcoholism and traumatic brain injury. Studies suggest that rTMS can improve brain function by protecting brain cells and aiding brain adaptation and change. Some early findings indicate that rTMS might reduce symptoms in people with alcohol use disorder and those who have had brain injuries. For example, it has been reported to change brain activity, which could aid recovery. This trial will explore different neural targets for rTMS, including custom neural anatomical targets and the Left Dorsolateral Prefrontal Cortex. While more research is needed, these results are promising for people dealing with these conditions. ^{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 Veterans who can read and speak English, have been diagnosed with alcohol use disorder (AUD) and mild traumatic brain injury (mTBI) according to specific criteria. They shouldn't have severe TBI, neurodegenerative diseases, psychotic disorders, low IQ scores (<70), or recent drug abuse. Pregnant/nursing individuals or those with MRI contraindications are excluded.

Inclusion Criteria

I have a mild traumatic brain injury according to SACA criteria.

You meet the criteria for Alcohol Use Disorder according to the DSM-5.

Exclusion Criteria

You have been identified as not putting in enough effort during the testing or have not been truthful about your symptoms.

You have been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder.

Pregnant or nursing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neuroimaging and Target Identification

Participants undergo neuroimaging to identify neural targets for rTMS treatment

2 weeks

1 visit (in-person)

Treatment

Participants receive 10 placebo and 10 active rTMS sessions targeting identified neural sites

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for changes in functional disability using WHODAS assessments

6 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P

Trial Overview The study aims to find a unique neural target in Veterans with AUD+mTBI for rTMS treatment to improve functional recovery. It will test the effectiveness of this target using the Magventure MagProX100 stimulator and Cool Coil B65 A/P as part of advancing rehabilitative health care in VAs nationwide.

How Is the Trial Designed?

Group I: Active + Placebo rTMS for Custom Neural Target Group 2 Active Control 1 Intervention

Custom neural anatomical target 2 defined by neuroimaging data

Group II: Active + Placebo rTMS for Custom Neural Target Group 1 Active Control 1 Intervention

Custom neural anatomical target 1 defined by neuroimaging data

Group III: Active + Placebo rTMS for Custom Neural Target Group 3 Active Control 1 Intervention

Custom neural anatomical target 3 defined by neuroimaging data

Group IV: Active + Placebo rTMS for Left DLPFC Neural Target Active Control 1 Intervention

Neural anatomical target will be the Left Dorsolateral Prefrontal Cortex identified using the 5cm from the motor "hot spot" rule.

Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

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 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 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 80 detoxified patients with alcohol use disorder, 10 sessions of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) did not significantly increase the number of abstinent days over a 6-month follow-up compared to a sham treatment.

HF-rTMS also showed no impact on alcohol craving levels, indicating that this treatment may not be effective as an add-on therapy for reducing alcohol use or cravings in patients with alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 10 add-on HF-rTMS treatment sessions on alcohol use and craving among detoxified inpatients with alcohol use disorder: a randomized sham-controlled clinical trial. Hoven, M., Schluter, RS., Schellekens, AF., et al.[2023]

Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral pre-frontal cortex significantly reduces craving for substances in patients with dependence, with a strong effect size (Hedges' g = -0.62) based on a meta-analysis of 26 randomized controlled trials involving 748 participants.

In addition to reducing cravings, rTMS also effectively decreases substance consumption, particularly when using excitatory stimulation protocols, indicating its potential as a therapeutic intervention for substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Zhang, JJQ., Fong, KNK., Ouyang, RG., et al.[2020]

The study involving 10 healthy volunteers demonstrated that repetitive transcranial magnetic stimulation (rTMS) using the Dantec MagPro stimulator is safe when applied at specific intensity and frequency settings, with no reported abnormalities in memory, verbal fluency, or hormone levels.

1 Hz stimulation at 125% of motor threshold significantly increased finger tapping rates, particularly in the hand opposite to the stimulation site, indicating a potential efficacy in enhancing motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and safety of a new repetitive transcranial magnetic stimulator. Wassermann, EM., Grafman, J., Berry, C., 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]

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]

A 53-year-old male with severe tinnitus following traumatic brain injury successfully underwent 5 series of repetitive transcranial magnetic stimulation (rTMS) without any side effects, suggesting that rTMS can be safely administered in such patients.

The treatment led to consistent improvements in tinnitus symptoms, as measured by validated questionnaires, indicating that rTMS may be an effective intervention for tinnitus associated with traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus after traumatic brain injury: a case study. Kreuzer, PM., Landgrebe, M., Frank, E., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03995173?tab=history&a=11

Record History | ver. 11: 2025-02-26 | NCT03995173 Eligible participants will be randomized to receive active or placebo rTMS. Participants will then complete motor thresholding (MT) to determine rTMS intensity.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03995173?tab=history&a=10

Record History | ver. 10: 2024-01-03 | NCT03995173 This is a prospective, pilot, double-blind randomized controlled trial of the intervention rTMS. There will be 2 groups of Veterans with AUD and co-occurring ...

3. withpower.com withpower.com/trial/phase-3-brain-injuries-2019-5ef93

Magnetic Brain Stimulation for TBI and Alcoholism Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury. [2022]. 2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4594992/

Repetitive Transcranial Magnetic Stimulation (rTMS) for the ... Preliminary guidelines for safe and effective use of repetitive transcranial magnetic stimulation in moderate to severe traumatic brain injury.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000658

Neuroprotective and plasticity promoting effects of ... Emerging evidence indicates that rTMS modulates microglial activation, promoting neuroprotective and plasticity-enhancing processes.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10119368/

PMC - PubMed Central Analgesic effects of directed repetitive transcranial magnetic stimulation in acute neuropathic pain after spinal cord injury. Pain Med ...