Repetitive Transcranial Magnetic Stimulation for Post-concussion Headaches

Study Overview
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Brief Summary
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This study aims to examine the long-term effect of repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, on chronic headaches following mild traumatic brain injury (mTBI). rTMS has been shown to be effective in reducing chronic headaches without side effects commonly seen in medications, such as sleepiness and addiction. This study uses rTMS to manage chronic headaches to improve post-concussion symptoms and reduce the economic burden due to delayed recovery. This project aims to better identify biomarkers for diagnosis and prognosis and maximize recovery from mTBI.

Official Title
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Using Repetitive Transcranial Magnetic Stimulation to Manage Headaches and Improve Rehabilitation Outcomes in Mild Traumatic Brain Injury: A Longitudinal Study

Conditions
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Brain Concussion, Mild Traumatic Brain Injury, Headache, Post-Concussion Symptoms

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation
* Device: Sham Repetitive Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 55 years old who were actively working prior to mTBI first-ever mTBI with loss of consciousness for less than 30 min, initial Glasgow Coma Scale between 13 and 15, or post-traumatic amnesia for ≤ 24 hours diagnosis of persistent post-traumatic headache according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria by a board-certified physician with subspecialty certification in Brain Injury Medicine headache develops within 7 days after head trauma headache persists for >=3 months after head trauma despite receiving standard care average persistent headache intensity is >= 3/10 of the numerical rating scale (NRS) on >=3days/week no evidence of radiculopathy or peripheral neuropathy on electromyography or clinical evaluation no evidence of other possible causes of headaches Exclusion Criteria: history of chronic headache diagnoses such as migraine, tension, or cluster headaches prior to the incidence of mTBI history of other neurologic conditions with medications affecting the central nervous system contraindications of receiving TMS (e.g., a history of epileptic seizure and having implants like a cardiac pacemaker or intracerebral vascular clip

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The Active rTMS group will receive 12 sessions (3 sessions/week) of rTMS and the Sham rTMS group will receive rTMS from a sham coil at the same location and duration as the Active rTMS group.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Repetitive transcranial magnetic stimulation (rTMS)<br>12 sessions (3 sessions/week) of active rTMS at the left motor cortex to upregulate brain excitability and reduce headaches and post-concussion symptoms. | Device: Repetitive Transcranial Magnetic Stimulation<br>* rTMS will be used to regulate the motor cortex to reduce headaches and post-concussion symptoms.<br>* Other names: Transcranial magnetic stimulation;|
| Sham Comparator: Sham rTMS<br>12 sessions (3 sessions/week) of sham rTMS will be administered at the same location and duration as the active rTMS but will not modulate brain function. After the study is completed, participants will be offered an opportunity to receive active rTMS. | Device: Sham Repetitive Transcranial Magnetic Stimulation<br>* Sham rTMS will be delivered by a sham coil as a comparator to the (active) rTMS. Sham rTMS will not change the brain function of the control group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily headache diary - intensity | Headaches will be documented by a daily headache diary during rTMS intervention about the intensity (by numerical rating scale). | daily documentation throughout the treatment course (4 weeks) | 
| Daily headache diary - frequency | Headaches will be documented by a daily headache diary during rTMS intervention about the frequency (by episode). | daily documentation throughout the treatment course (4 weeks) | 
| Daily headache diary - duration | Headaches will be documented by a daily headache diary during rTMS intervention about the duration (by hour). | daily documentation throughout the treatment course (4 weeks) | 
| Patient-Reported Outcomes Measurement Information System (PROMIS) | The PROMIS questionnaires with subsections of 1) pain interference, 2) pain behavior, 3) sleep disturbance, 4) sleep-related impairment will be used as patient-reported outcomes of pain and sleep. For all subsections, on a scale of 1 to 5, higher numbers indicate worse outcomes. | baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up | 
| Headache impact test 6 (HIT-6) | The HIT-6 will be used to assess the impact of headaches on one's ability to function in occupational and social lives. On a scale of 36 to 78, higher numbers indicate worse outcomes. | baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up | 
| Post-Concussion Symptom Scale (PCSS) | The change in global post-concussion symptoms will be measured by the PCSS. On a scale of 1 to 5, higher numbers indicate worse outcomes. | baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up | 
| Rivermead Post-Concussion Symptoms Questionnaire (RPQ) | The change in global post-concussion symptoms will be measured by the RPQ. On a scale of 0 to 4, higher numbers indicate worse outcomes. | baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up | 
| Wrist actigraphy - sleep quality | Kinematic assessments by the wrist actigraphy will be worn to measure sleep quality. | baseline, immediately post-treatment (completion of rTMS) | 
| Wrist actigraphy - physical activity level | Kinematic assessments by the wrist actigraphy will be worn to measure physical activity level. | baseline, immediately post-treatment (completion of rTMS) | 
| Neurophysiological measures by TMS | Neurophysiology will be measured by TMS to indicate changes in brain function. | baseline, immediately post-treatment (completion of rTMS) | 
| Gene expression | Peripheral blood will be collected to measure mRNA to impute gene expression. | baseline, immediately post-treatment (completion of rTMS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of rehabilitation (LOR) | LOR will be recorded by reviewing the medical chart. | 3-month follow-up | 
| Return to work (RTW) | RTW will be will be calculated as the percent of time working relative to the pre-mTBI workload. | 3-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive transcranial magnetic stimulation, Non-invasive brain stimulation, Neuromodulation, Chronic pain, Biomarkers