rTMS and Headache Management for mTBI-Related Headaches

Overseen By Caleb Lopez, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Veterans Medical Research Foundation

Disqualifiers: Pregnant, Pacemaker, Dementia, Seizure, others

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

Compensation: Varies

Number of Visits: 30

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of repetitive transcranial magnetic stimulation (rTMS) combined with telehealth therapy in managing headaches after a mild traumatic brain injury (mTBI). Researchers believe that rTMS and telehealth therapy together might reduce headache frequency and severity more effectively than placebo treatments. Participants will receive either active or sham (fake) rTMS and will engage in telehealth sessions focused on headache education or management. Individuals who have experienced persistent headaches for more than three months after an mTBI and have not tried rTMS before might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatment combinations for managing post-mTBI headaches.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What prior data suggests that rTMS and telehealth therapy are safe for managing mTBI-related headaches?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for people. Studies have found that rTMS can be safely used on both healthy individuals and those with brain conditions, provided it adheres to current safety guidelines. This treatment can help reduce chronic headaches without causing side effects like sleepiness or addiction, which are common with some medications.

Additionally, rTMS is already used to treat other conditions, such as depression, and has proven effective even in people with mild traumatic brain injuries (mTBI). This suggests that the treatment is well-tolerated. Overall, evidence supports rTMS as a safe option for managing headaches related to mTBI. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using repetitive Transcranial Magnetic Stimulation (rTMS) for managing mTBI-related headaches because it offers a novel approach by targeting the brain's left dorsolateral prefrontal cortex. Unlike traditional treatments like medications and cognitive therapies that often focus on symptom management, rTMS aims to directly modulate brain activity, potentially addressing the root cause of headaches. This non-invasive technique could provide faster relief with fewer side effects compared to conventional drug therapies. Additionally, integrating telehealth headache management and education elevates the accessibility and comprehensiveness of care, paving the way for more personalized treatment strategies.

What evidence suggests that this trial's treatments could be effective for mTBI-related headaches?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) effectively reduces headaches caused by mild traumatic brain injury (mTBI). Studies have found that rTMS can lower headache intensity by up to 56.3%. This method uses magnetic fields to stimulate nerves in the brain, which helps manage these headaches. In this trial, some participants will receive active rTMS combined with telehealth headache education or management therapy. Telehealth headache management therapy provides patients with guidance and strategies to better handle their headaches. Together, rTMS and telehealth therapy offer a promising way to manage headaches related to mTBI. ^{1 5 6 7 8}

Who Is on the Research Team?

Albert Y Leung, MD

Principal Investigator

San Diego Veterans Healthcare System

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who have had a mild traumatic brain injury (mTBI) and suffer from persistent headaches that started after their injury. They must not have received TMS treatment before, and their headache intensity should be over 30 on a scale of 100. People with metal implants, seizure history, major psychiatric diseases, or chronic pain conditions other than mTBI-related headaches cannot participate.

Inclusion Criteria

I did not have daily headaches before my mild brain injury.

I experience severe headaches rated over 30 on a scale of 100.

I have had a mild traumatic brain injury.

Exclusion Criteria

I cannot understand English.

I have had seizures in the past.

I had chronic headaches or migraines before my brain injury.

Timeline for a Trial Participant

Pre-Treatment Assessments

Participants are screened for eligibility to participate in the trial and undergo baseline assessments with MRI scan

2 weeks

2 visits (in-person)

Induction Treatment

Participants receive 10 weekday neuronavigation guided rTMS sessions

2 weeks

10 visits (in-person)

Post-Treatment Assessments and Maintenance Treatment

Participants undergo post-induction treatment assessments and maintenance treatments

20 weeks

7 visits (in-person)

Telehealth Therapy/Education

Participants receive telehealth therapy or education sessions

8 weeks

11 sessions (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active rTMS
• Headache Education Control
• Headache Management Therapy
• Sham rTMS

Trial Overview The study tests if active repetitive transcranial magnetic stimulation (rTMS), combined with telehealth therapy, can reduce headaches caused by mild traumatic brain injuries better than placebo treatments. Participants will either receive the real rTMS treatment along with headache management therapy or sham rTMS with basic headache education.

How Is the Trial Designed?

Group I: Sham rTMS with telehealth headache management therapy Experimental Treatment 2 Interventions

Participants receive sham rTMS treatment at the left dorsolateral prefrontal cortex and therapy for headache management

Group II: Active rTMS with telehealth headache education control Experimental Treatment 2 Interventions

Participants receive active rTMS treatment at the left dorsolateral prefrontal cortex and headache education

Group III: Active rTMS with telehealth headache management therapy Active Control 2 Interventions

Participants receive both active rTMS treatment at the left dorsolateral prefrontal cortex and therapy for headache management

Group IV: Sham rTMS with telehealth headache education control Placebo Group 2 Interventions

Participants receive sham rTMS treatment at the left dorsolateral prefrontal cortex and headache education

Active rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Smoking Cessation
• Chronic Pain Syndrome

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Chronic Pain Syndrome
• Generalized Anxiety Disorder (GAD)
• Bipolar Disorder

Who Is Running the Clinical Trial?

Veterans Medical Research Foundation

Lead Sponsor

Trials

46

Recruited

5,100+

Published Research Related to This Trial

In a pilot study involving 30 patients with chronic tension-type headache (CTTH), low-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced pain levels and increased pain thresholds compared to a placebo, indicating its potential efficacy as a treatment.

Subjective assessments showed improvements in pain ratings and psychological factors, suggesting that rTMS may not only alleviate pain but also positively impact anxiety and pain beliefs, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in chronic tension-type headache: A pilot study. Mattoo, B., Tanwar, S., Bhatia, R., et al.[2020]

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) is a safe and effective non-invasive treatment for depression, with a low seizure risk of less than 0.1%.

Common side effects like headache and discomfort typically decrease with continued treatment, highlighting the importance of monitoring patient safety and medication interactions during rTMS sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application and Safety of rTMS in Japan and Overseas]. Kito, S.[2015]

Single-pulse transcranial magnetic stimulation (sTMS) has been shown to be a low-risk technique with minimal adverse events, making it a promising option for diagnosing and treating neurological and psychiatric conditions, including migraines.

Extensive clinical experience over two decades indicates that sTMS does not cause harm to brain tissue or neurophysiological function, supporting its safety as a nonpharmacologic treatment for acute migraine headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for migraine: a safety review. Dodick, DW., Schembri, CT., Helmuth, M., et al.[2010]

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) 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 small study of 6 men with mild traumatic brain injury-related headaches (MTBI-HA), repetitive transcranial magnetic stimulation (rTMS) significantly reduced average headache intensity by 53% and the frequency of severe headache episodes by nearly 79%.

The rTMS treatment was well tolerated, suggesting it could be a promising non-invasive therapy for managing chronic pain from MTBI-HA, warranting further investigation in larger randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS in Alleviating Mild TBI Related Headaches--A Case Series. Leung, A., Fallah, A., Shukla, S., et al.[2018]

In a study involving 26 participants with mild traumatic brain injury (MTBI) and persistent headaches, real repetitive transcranial magnetic stimulation (rTMS) significantly reduced headache frequency and intensity one week after treatment, while sham treatment showed no such effects.

fMRI results indicated that real rTMS enhanced functional connectivity in the left prefrontal cortex, which is crucial for pain modulation, suggesting that rTMS may improve the brain's ability to manage pain in MTBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

fMRI findings in MTBI patients with headaches following rTMS. Vaninetti, M., Lim, M., Khalaf, A., et al.[2022]

Citations

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Long-term Efficacy of Repetitive Transcranial Magnetic ... Long-term Efficacy of Repetitive Transcranial Magnetic Stimulation at Motor Cortex for Mild Traumatic Brain Injury-Related Headaches.

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Long-term Efficacy of Repetitive Transcranial Magnetic ... Long-term Efficacy of Repetitive Transcranial Magnetic Stimulation at Motor Cortex for Mild Traumatic Brain Injury-Related Headaches. Author ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03314584

Managing Mild Traumatic Brain Injury Related Headaches ... This study aims to assess the long-term effect of repetitive transcranial magnetic stimulation (rTMS) in managing MTBI related headaches for up to 2-3 months by ...

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT05176392

Combined Transcranial Magnetic Stimulation and Therapy ... The investigators hypothesize that active rTMS combined with telehealth therapy will provide marked reduction in mTBI related headaches and ...

5. research.va.gov research.va.gov/currents/1115-7.cfm

Can magnetic stimulation help TBI headaches? A small study involving Veterans with headaches related to mild traumatic brain injury found positive results from a treatment called repetitive transcranial ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06112093?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(manage%20syndrome%20OR%20%22mirage%22%20OR%20%22%20myelodysplasia-infection-restriction%20of%20growth-adrenal%20hypoplasia-genital%20anomalies-enteropathy%20syndrome%22%20OR%20%22%20myelodysplasia-infection-restriction%20of%20growth-adrenal%20hypoplasia-genital%20phenotypes-enteropathy%20syndrome%22%20OR%20%22%20myelodysplasia,%20infection,%20restriction%20of%20Growth,%20adrenal%20Hypoplasia,%20genital%20phenotypes,%20and%20enteropathy%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING))&rank=4

Repetitive Transcranial Magnetic Stimulation for Post- ... rTMS has been shown to be effective in reducing chronic headaches without side effects commonly seen in medications, such as sleepiness and addiction. This ...

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Repetitive transcranial magnetic stimulation for depression ... Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9879417/

Safety Review for Clinical Application of Repetitive ... rTMS conforming to the current safety guidelines (Tables 3, 4, 5) can be applied safely to both healthy volunteers and patients with acquired brain diseases ...