Using Repetitive Transcranial Magnetic Stimulation to Manage Headaches and Improve Rehabilitation Outcomes in Mild Traumatic Brain Injury: A Longitudinal Study
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Gene expression
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •18 - 55 years old
- •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
- •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
Arms & Interventions
Moderate-dose rTMS
12 sessions (1 session/day, 3 days/week for 4 weeks) of active rTMS
Intervention: Repetitive Transcranial Magnetic Stimulation (Device)
Sham rTMS
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.
Intervention: Sham Repetitive Transcranial Magnetic Stimulation (Device)
High-dose rTMS
24 sessions (4 sessions/day, 3 days/week for 2 weeks) of active rTMS
Intervention: Repetitive Transcranial Magnetic Stimulation (Device)
Low-dose rTMS
6 sessions (1 session/day, 3 days/week for 2 weeks) of active rTMS
Intervention: Repetitive Transcranial Magnetic Stimulation (Device)
Outcomes
Primary Outcomes
Gene expression
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Peripheral blood will be collected to measure mRNA to impute gene expression.
Headache impact test 6 (HIT-6)
Time Frame: baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up, 6-month follow-up
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.
Post-Concussion Symptom Scale (PCSS)
Time Frame: baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up, 6-month follow-up
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.
Daily headache diary
Time Frame: daily documentation throughout the treatment course (4 weeks)
Composite headache score will be calculated as average intensity (NRS) × average frequency (episode/day) × average duration (hours/episode).
Patient-Reported Outcomes Measurement Information System (PROMIS)
Time Frame: baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up, 6-month follow-up
The PROMIS questionnaires with subsections of 1) pain interference, 2) pain behavior 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.
Wrist actigraphy - physical activity level
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Kinematic assessments by the wrist actigraphy will be worn to measure physical activity level.
Neurophysiological measures by TMS
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Neurophysiology will be measured by TMS to indicate changes in brain function.
Daily headache diary
Time Frame: daily documentation throughout the treatment course (4 weeks)
Composite headache score will be calculated as average intensity (NRS) × average frequency (episode/day) × average duration (hours/episode).
Patient-Reported Outcomes Measurement Information System (PROMIS)
Time Frame: baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up, 6-month follow-up
The PROMIS questionnaires with subsections of 1) pain interference, 2) pain behavior 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.
Protein expression
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Peripheral blood will be collected to measure protein expression
Neurophysiological measures by TMS
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Neurophysiology will be measured by TMS to indicate changes in brain function.
Headache impact test 6 (HIT-6)
Time Frame: baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up, 6-month follow-up
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.
Post-Concussion Symptom Scale (PCSS)
Time Frame: baseline, immediately post-treatment (completion of rTMS), 1-month follow-up, 3-month follow-up, 6-month follow-up
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.
Wrist actigraphy - physical activity level
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Kinematic assessments by the wrist actigraphy will be worn to measure physical activity level.
Gene expression
Time Frame: baseline, immediately post-treatment (completion of rTMS)
Peripheral blood will be collected to measure mRNA to impute gene expression.
Secondary Outcomes
- Wrist actigraphy - sleep quality(baseline, immediately post-treatment (completion of rTMS))
Investigators
Yi-Ling Kuo, PT, PhD
Assistant Professor
State University of New York - Upstate Medical University