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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The objectives of this VA Merit application are to identify a neural target unique to Veterans with co-occurring alcohol use disorder and mild traumatic brain injury (AUD+mTBI) and to test the efficacy of this target as a stimulation site for repetitive transcranial magnetic stimulation (rTMS) treatment to maximize functional recovery. rTMS will soon be a treatment option at 30 VAs nationwide and preliminary studies show promise for AUD and mTBI treatment. A better understanding of how AUD+mTBI impacts the brain needs to occur in order to advance rTMS to optimize function. This research is aligned with the VA RR\&D's mission to generate knowledge and innovations to advance the rehabilitative health and care of Veterans, to effectively integrate clinical and applied rehabilitation research, and translate research results into practice. This research is also aligned with the goal of the Psychological Health \& Social Reintegration portfolio to develop interventions improving psychological health status of Veterans enabling them to function more fully in society.

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 data supports the idea that Magnetic Brain Stimulation for TBI and Alcoholism is an effective treatment?

The available research shows that Magnetic Brain Stimulation, specifically repetitive transcranial magnetic stimulation (rTMS), is promising for treating alcohol addiction. Studies indicate that rTMS can reduce cravings and alcohol consumption when applied to a specific part of the brain called the dorsolateral prefrontal cortex. For example, one study found that high-frequency rTMS sessions helped reduce alcohol use and cravings in patients with alcohol use disorder. Additionally, in the context of traumatic brain injury (TBI), rTMS was shown to improve symptoms of depression in a patient, suggesting potential benefits for TBI-related conditions. Overall, while more research is needed, these findings suggest that rTMS could be an effective treatment for both alcohol addiction and TBI-related issues. ^{1 2 3 4 5}

What data supports the effectiveness of this treatment for TBI and Alcoholism?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can reduce cravings and consumption in people with alcohol addiction when applied to a specific brain area. Additionally, rTMS has been used safely in a case study for improving depression in a person with traumatic brain injury (TBI), suggesting potential benefits for TBI-related conditions. ^{1 2 3 4 5}

What safety data exists for magnetic brain stimulation in TBI and alcoholism?

The safety of repetitive transcranial magnetic stimulation (rTMS) has been evaluated in various studies. For TBI, guidelines suggest that rTMS can be safely used with careful protocol selection, as demonstrated in a case study where a patient tolerated the treatment well without side effects. For alcoholism, studies indicate that rTMS is generally safe, with no significant abnormalities found in healthy volunteers using the MagPro stimulator. However, results on its effectiveness in reducing alcohol use and craving are mixed. Overall, rTMS appears safe at specific intensity, frequency, and duration combinations. ^{1 2 3 6 7}

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

Research indicates that repetitive transcranial magnetic stimulation (rTMS) is generally safe for humans when used at specific settings. Studies have shown it to be well tolerated with no side effects in patients with traumatic brain injury and healthy volunteers, provided that appropriate protocols are followed to minimize risks such as seizures. ^{1 2 3 6 7}

Is the treatment Magnetic Brain Stimulation promising for TBI and Alcoholism?

Yes, Magnetic Brain Stimulation, also known as repetitive transcranial magnetic stimulation (rTMS), is promising for treating alcoholism by reducing cravings and alcohol use. It also shows potential in improving symptoms related to traumatic brain injury, such as depression and tinnitus, without significant side effects. ^{1 3 4 5 8}

How does the treatment of repetitive transcranial magnetic stimulation (rTMS) differ from other treatments for TBI and alcoholism?

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, which can help reduce cravings and improve symptoms in conditions like alcohol dependence and traumatic brain injury. Unlike medications, rTMS directly targets brain activity and has shown promise in reducing alcohol cravings and improving mood without the need for drugs. ^{1 3 4 5 8}

Research Team

Amy A Herrold, PhD BA

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

2. England 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. [2020]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study. [2022]

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. Ireland pubmed.ncbi.nlm.nih.gov

Use and safety of a new repetitive transcranial magnetic stimulator. [2022]

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

Repetitive transcranial magnetic stimulation for the treatment of chronic tinnitus after traumatic brain injury: a case study. [2022]