rTMS for Post-Concussion Syndrome

Overseen By Yi-Ling Kuo, PT, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: State University of New York - Upstate Medical University

Must not be taking: CNS medications

Disqualifiers: Chronic headaches, Neurologic conditions, others

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

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

Compensation: Varies

Number of Visits: 13

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain therapy, might help people with persistent headaches following a mild concussion. The goal is to determine if rTMS can effectively reduce these headaches, which often resist regular treatments and can seriously impact daily life. Participants will be divided into groups to receive varying amounts of rTMS or a sham treatment. Individuals with persistent headaches that began within a week of a concussion and continued for over three months might be suitable for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a history of neurologic conditions with medications affecting the central nervous system, you may be excluded from participating.

What prior data suggests that this technique is safe for managing chronic headaches?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for individuals who have recently experienced a concussion. Studies have used rTMS without causing common medication side effects such as drowsiness or addiction. The risk of a seizure from rTMS is less than 1%, which is very low. Importantly, past patients have reported that rTMS can alleviate long-lasting headaches following a concussion. Overall, rTMS is considered a safe option for managing post-concussion symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive approach to treating Post-Concussion Syndrome, unlike the standard care options that often include medication and rest. Most treatments for this condition focus on symptom management, but rTMS targets the brain's electrical activity directly, which could address the root cause of symptoms. Researchers are particularly excited about rTMS because it has the potential to provide faster relief and recovery with different dosing protocols, such as moderate-dose, high-dose, and low-dose regimens, each offering tailored benefits depending on the patient's needs. Additionally, the sham rTMS arm ensures that any improvements can be confidently attributed to the active treatments, strengthening the validity of the results.

What evidence suggests that this trial's treatments could be effective for post-concussion syndrome?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can alleviate long-lasting headaches following a concussion. Studies have found that rTMS reduces headaches without causing side effects such as sleepiness and addiction, often associated with medication. Some patients have also reported improved memory and mood after rTMS treatment. This trial will compare different doses of rTMS—moderate-dose, high-dose, and low-dose—as well as a sham rTMS group. Overall, rTMS provides a non-invasive option to potentially relieve ongoing symptoms after a mild brain injury. ^{3 6 7 8 9}

Who Is on the Research Team?

Yi-Ling Kuo, PT, PhD

Principal Investigator

State University of New York - Upstate Medical University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 who developed headaches within a week after a mild brain injury and have had these headaches persist for at least 3 months despite treatment. Participants must have been working before the injury, lost consciousness for less than 30 minutes, and not have other neurological conditions or chronic headache history.

Inclusion Criteria

I have had headaches for 3 months or more after a head injury, despite treatment.

I am between 18 and 55 years old and was working before my mild brain injury.

I had a mild brain injury with brief unconsciousness or confusion.

Exclusion Criteria

I had chronic headaches like migraine before my brain injury.

I take medication for a brain or nerve condition.

I don't have epilepsy, a pacemaker, or brain vessel clips.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 12 sessions of active or sham rTMS over 4 weeks to manage chronic headaches and improve post-concussion symptoms

4 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at multiple follow-up points

6 months

Follow-up assessments at 1, 3, and 6 months

Open-label extension (optional)

Participants may opt into receiving active rTMS after the study is completed

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation
• Sham Repetitive Transcranial Magnetic Stimulation

Trial Overview

The study tests repetitive transcranial magnetic stimulation (rTMS), which uses magnetic fields to stimulate nerve cells in the brain. It's compared with sham rTMS to see if it can reduce long-term headaches caused by mild traumatic brain injuries without medication side effects.

How Is the Trial Designed?

Group I: Moderate-dose rTMS Active Control 1 Intervention

12 sessions (1 session/day, 3 days/week for 4 weeks) of active rTMS

Group II: High-dose rTMS Active Control 1 Intervention

24 sessions (4 sessions/day, 3 days/week for 2 weeks) of active rTMS

Group III: Low-dose rTMS Active Control 1 Intervention

6 sessions (1 session/day, 3 days/week for 2 weeks) of active rTMS

Group IV: Sham rTMS Placebo Group 1 Intervention

12 sessions (1 session/day, 3 days/week for 4 weeks) of sham rTMS will be administered at the same location and duration as the Moderate-rTMS protocol. After the study is completed, participants will be offered an opportunity to receive active rTMS.

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

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

State University of New York - Upstate Medical University

Lead Sponsor

Trials

176

Recruited

27,600+

Published Research Related to This Trial

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]

In a study of 22 participants with persistent post-concussion syndrome (PCS), those who received Active Repetitive Transcranial Magnetic Stimulation (rTMS) showed significant improvements in symptoms compared to those who received Sham treatment, particularly in individuals with injuries less than 12 months old.

The improvements were measured using the Rivermead Post-Concussion Symptoms Questionnaire, with notable symptom reduction observed at 1 and 2 months post-treatment, indicating that rTMS may be a safe and effective option for treating recent concussions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Randomised Double-Blind Study of the Tolerability and efficacy of repetitive Transcranial Magnetic Stimulation on Persistent Post-Concussion Syndrome. Moussavi, Z., Suleiman, A., Rutherford, G., et al.[2021]

Transcranial magnetic stimulation (TMS) is a painless technique that can stimulate the brain and potentially improve brain function by altering neuronal excitability and promoting brain plasticity.

Repetitive TMS (rTMS) has shown positive therapeutic effects in individuals with motor disorders and psychiatric conditions, indicating its potential as a promising treatment for traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation: a possible treatment for TBI. Pape, TL., Rosenow, J., Lewis, G.[2019]

In a pilot study involving 15 patients with mild traumatic brain injury (mTBI), twice-daily low frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex was found to be safe and well-tolerated, with no serious adverse events reported.

The treatment led to significant improvements in post-concussion symptoms, pain, and mood, as well as cognitive enhancements in areas like verbal fluency and working memory, suggesting rTMS may be an effective intervention for managing chronic symptoms after concussion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated repetitive transcranial magnetic stimulation in the treatment of post-concussion symptoms due to mild traumatic brain injury: a pilot study. Meek, BP., Hill, S., Modirrousta, M.[2021]

Repetitive transcranial magnetic stimulation (rTMS) shows promising preliminary results in treating post-concussive symptoms, particularly for depression and headaches, based on a systematic review of 11 studies involving small pilot samples.

While rTMS demonstrated positive outcomes in some studies, the overall methodological diversity and small sample sizes highlight the need for further research to confirm its efficacy in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for the Treatment of Concussion: A Systematic Review. Mollica, A., Safavifar, F., Fralick, M., 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) has been found to be safe for military service members with concussions, showing no reports of seizures or increased adverse events compared to general rTMS studies.

However, the evidence supporting the effectiveness of rTMS in treating neuropsychiatric and neurocognitive symptoms following concussions is currently limited, indicating a need for more comprehensive research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Repetitive Transcranial Magnetic Stimulation in the Treatment of Neuropsychiatric and Neurocognitive Symptoms Associated With Concussion in Military Populations. Oberman, LM., Exley, S., Philip, NS., 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) 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]

A clinical trial involving 44 adults with persistent postconcussion syndrome (PPCS) is investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) compared to sham treatment, aiming to reduce symptom burden and improve quality of life.

The study will also utilize functional near-infrared spectroscopy (fNIRS) to explore the neurological changes associated with rTMS treatment, potentially enhancing our understanding of its mechanism in alleviating PPCS symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Persistent Postconcussion Syndrome With Repetitive Transcranial Magnetic Stimulation Using Functional Near-Infrared Spectroscopy as a Biomarker of Response: Protocol for a Randomized Controlled Clinical Trial. du Plessis, S., Oni, IK., Lapointe, AP., et al.[2022]

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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

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Most treatment recommendations for TMS-related seizures are supportive in nature. The risk of TMS-related seizures is <1% overall. TMS has ...

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