Repetitive Transcranial Magnetic Stimulation for Post-concussion Headaches
Using Repetitive Transcranial Magnetic Stimulation to Manage Headaches and Improve Rehabilitation Outcomes in Mild Traumatic Brain Injury: A Longitudinal Study
1 other identifier
interventional
60
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2023
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 23, 2023
CompletedStudy Start
First participant enrolled
October 23, 2023
CompletedFirst Posted
Study publicly available on registry
November 1, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 23, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 23, 2027
October 10, 2025
October 1, 2025
3 years
October 23, 2023
October 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
Daily headache diary
Composite headache score will be calculated as average intensity (NRS) Ă— average frequency (episode/day) Ă— average duration (hours/episode).
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 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, 6-month follow-up
Protein expression
Peripheral blood will be collected to measure protein expression
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)
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, 6-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, 6-month follow-up
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)
Gene expression
Peripheral blood will be collected to measure mRNA to impute gene expression.
baseline, immediately post-treatment (completion of rTMS)
Secondary Outcomes (1)
Wrist actigraphy - sleep quality
baseline, immediately post-treatment (completion of rTMS)
Study Arms (4)
Moderate-dose rTMS
ACTIVE COMPARATOR12 sessions (1 session/day, 3 days/week for 4 weeks) of active rTMS
Sham rTMS
SHAM COMPARATOR12 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.
High-dose rTMS
ACTIVE COMPARATOR24 sessions (4 sessions/day, 3 days/week for 2 weeks) of active rTMS
Low-dose rTMS
ACTIVE COMPARATOR6 sessions (1 session/day, 3 days/week for 2 weeks) of active rTMS
Interventions
rTMS will be used to regulate the motor cortex to reduce headaches and post-concussion symptoms.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Related Publications (21)
Iverson GL, Gardner AJ, Terry DP, Ponsford JL, Sills AK, Broshek DK, Solomon GS. Predictors of clinical recovery from concussion: a systematic review. Br J Sports Med. 2017 Jun;51(12):941-948. doi: 10.1136/bjsports-2017-097729.
PMID: 28566342BACKGROUNDDe Kruijk JR, Leffers P, Menheere PP, Meerhoff S, Rutten J, Twijnstra A. Prediction of post-traumatic complaints after mild traumatic brain injury: early symptoms and biochemical markers. J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):727-32. doi: 10.1136/jnnp.73.6.727.
PMID: 12438478BACKGROUNDMinen MT, Boubour A, Walia H, Barr W. Post-Concussive Syndrome: a Focus on Post-Traumatic Headache and Related Cognitive, Psychiatric, and Sleep Issues. Curr Neurol Neurosci Rep. 2016 Nov;16(11):100. doi: 10.1007/s11910-016-0697-7.
PMID: 27709555BACKGROUNDBomyea J, Lang AJ, Delano-Wood L, Jak A, Hanson KL, Sorg S, Clark AL, Schiehser DM. Neuropsychiatric Predictors of Post-Injury Headache After Mild-Moderate Traumatic Brain Injury in Veterans. Headache. 2016 Apr;56(4):699-710. doi: 10.1111/head.12799. Epub 2016 Mar 29.
PMID: 27028095BACKGROUNDHoward L, Schwedt TJ. Posttraumatic headache: recent progress. Curr Opin Neurol. 2020 Jun;33(3):316-322. doi: 10.1097/WCO.0000000000000815.
PMID: 32304441BACKGROUNDRossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.
PMID: 25797650BACKGROUNDRossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmoller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020. Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021 Jan;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. Epub 2020 Oct 24.
PMID: 33243615BACKGROUNDMajor BP, Rogers MA, Pearce AJ. Using transcranial magnetic stimulation to quantify electrophysiological changes following concussive brain injury: a systematic review. Clin Exp Pharmacol Physiol. 2015 Apr;42(4):394-405. doi: 10.1111/1440-1681.12363.
PMID: 25603731BACKGROUNDLeung A, Shukla S, Fallah A, Song D, Lin L, Golshan S, Tsai A, Jak A, Polston G, Lee R. Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. Neuromodulation. 2016 Feb;19(2):133-41. doi: 10.1111/ner.12364. Epub 2015 Nov 10.
PMID: 26555886BACKGROUNDLeung A, Fallah A, Shukla S, Lin L, Tsia A, Song D, Polston G, Lee R. rTMS in Alleviating Mild TBI Related Headaches--A Case Series. Pain Physician. 2016 Feb;19(2):E347-54.
PMID: 26815263BACKGROUNDChoi GS, Kwak SG, Lee HD, Chang MC. Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study. J Rehabil Med. 2018 Feb 28;50(3):246-252. doi: 10.2340/16501977-2321.
PMID: 29392332BACKGROUNDHess JL, Tylee DS, Barve R, de Jong S, Ophoff RA, Kumarasinghe N, Tooney P, Schall U, Gardiner E, Beveridge NJ, Scott RJ, Yasawardene S, Perera A, Mendis J, Carr V, Kelly B, Cairns M; Neurobehavioural Genetics Unit; Tsuang MT, Glatt SJ. Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia. Schizophr Res. 2016 Oct;176(2-3):114-124. doi: 10.1016/j.schres.2016.07.006. Epub 2016 Jul 20.
PMID: 27450777BACKGROUNDHiskens MI, Schneiders AG, Angoa-Perez M, Vella RK, Fenning AS. Blood biomarkers for assessment of mild traumatic brain injury and chronic traumatic encephalopathy. Biomarkers. 2020 May;25(3):213-227. doi: 10.1080/1354750X.2020.1735521. Epub 2020 Mar 12.
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PMID: 22917206BACKGROUNDHess JL, Quinn TP, Zhang C, Hearn GC, Chen S; Neuropsychiatric Consortium for Analysis and Sharing of Transcriptomes; Kong SW, Cairns M, Tsuang MT, Faraone SV, Glatt SJ. BrainGENIE: The Brain Gene Expression and Network Imputation Engine. Transl Psychiatry. 2023 Mar 22;13(1):98. doi: 10.1038/s41398-023-02390-w.
PMID: 36949060BACKGROUNDLefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1.
PMID: 31901449BACKGROUNDAskew RL, Cook KF, Revicki DA, Cella D, Amtmann D. Evidence from diverse clinical populations supported clinical validity of PROMIS pain interference and pain behavior. J Clin Epidemiol. 2016 May;73:103-11. doi: 10.1016/j.jclinepi.2015.08.035. Epub 2016 Feb 27.
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PMID: 31399612BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yi-Ling Kuo, PT, PhD
State University of New York - Upstate Medical University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
October 23, 2023
First Posted
November 1, 2023
Study Start
October 23, 2023
Primary Completion (Estimated)
October 23, 2026
Study Completion (Estimated)
October 23, 2027
Last Updated
October 10, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be available no later than upon the publication of the final dataset.
- Access Criteria
- Study personnel on the list approved by the Institutional Review Board and researchers outside of this project as approved by the Principal Investigator
The study investigators will make the de-identified data available to users for research purposes. Sharing and modification rights of the study data will be determined for individual users by the Principal Investigator.