Repetitive Transcranial Magnetic Stimulation Paired with Augmented Reality to Alter Concussion Symptoms

NCT06735157 | Not Yet Recruiting

• 1 other identifier: 17699
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to determine whether the delivery of brain stimulation paired with a balance training task can improve symptoms of dizziness for individuals experiencing these symptoms due to concussion. The main questions it aims to answer are:

• Does repetitive transcranial magnetic stimulation (rTMS) paired with balance training improve the symptoms of dizziness in individuals with persistent dizziness due to concussion?
• Is the proposed rTMS and balance training protocol feasible in this population? Researchers will compare results from a sham rTMS group with those from a real rTMS group to see if any observed changes are from the placebo effect rather than the expected effects of real rTMS. Participants will receive pulses of rTMS to the area of the brain responsible for control of movement and then be asked to interact with digital objects using augmented reality glasses for 14 days over 3 weeks.

Conditions

Mild Traumatic Brain Injury, Concussion; Chronic Dizziness; Vestibular Problem

Keywords

Concussion; Dizziness; Transcranial magnetic stimulation; augmented reality; repetitive transcranial magnetic stimulation; mild traumatic brain injury; intermittent theta burst stimulation; accelerated iTBS; balance training; vestibular rehabilitation therapy

Outcome Measures

Primary Outcomes (1)

• Dizziness Handicap Inventory (DHI)

  The DHI is a well-validated 25-item questionnaire which will be used to assess functional, physical, and emotional domains of disability due to dizziness. The test has a total possible score of 100 points, whereby 16-34 = mild handicap, 36-52 = moderate handicap, and 54+ = severe handicap.

  At baseline (before the first intervention session) and post-intervention (following the final intervention session)

Secondary Outcomes (9)

• Balance Error Scoring System (BESS)

  At baseline (before the first intervention session) and post-intervention (following the final intervention session)

• Activities-Specific Balance Confidence (ABC) Scale

  At baseline (before the first intervention session) and post-intervention (following the final intervention session)

• Rivermead Post Concussion Symptoms Questionnaire (RPSQ-3 and RPSQ-13)

  At baseline (before the first intervention session) and post-intervention (following the final intervention session)

• PROMIS-29

  At baseline (before the first intervention session) and post-intervention (following the final intervention session)

• Motor evoked potential (MEP)

  At baseline (before the first intervention session) and post-intervention (following the final intervention session)

Study Arms (2)

Sham rTMS

SHAM COMPARATOR

Behavioral: Augmented reality vestibular rehabilitation therapy; Device: SHAM repetitive transcranial magnetic stimulation

Real rTMS

ACTIVE COMPARATOR

Device: Repetitive transcranial magnetic stimulation; Behavioral: Augmented reality vestibular rehabilitation therapy

Interventions

Repetitive transcranial magnetic stimulation DEVICE

Repetitive transcranial magnetic stimulation (intermittent theta burst stimulation) will be delivered using a Magstim Rapid 2 stimulator (Magstim, Whitland, UK) guided using neuronavigation (Brainsight, Rogue Research, Montreal, QC, Canada) to target primary motor cortex. Participants will receive 14 days of stimulation over a 3-week period. Stimulation will use a protocol called accelerated iTBS (Duprat et al., 2016) whereby iTBS will be delivered three times during the same study session. Each iTBS session will deliver 600 pulses in 50 Hz bursts of 3 pulses for a total of 1800 pulses delivered each day. iTBS sessions will each be separated by 15 minutes (Duprat et al., 2016; Wu et al., 2013). Stimulation will be delivered at 70% of the participant's resting motor threshold. Immediately following each 600-pulse period of iTBS, individuals will participate in 5 to 10 minutes of AR vestibular rehabilitation therapy.

Also known as: Intermittent theta burst stimulation

Real rTMS

Augmented reality vestibular rehabilitation therapy BEHAVIORAL

Participants will complete the vestibular training through Nreal Air AR Glasses (Nreal, China). The vestibular training task was custom-made in Unity V2021.3.14fI software using C+ script language. Participants will be standing upright for the AR training, with a safety bar positioned directly in front of them should they need to hold onto something. A large cross-shaped target will be positioned approximately 3 feet in front of the participant's head with its vertical center aligned with the participant's midline. This will act as a visual starting point. The training is adapted from clinical vestibular rehabilitation training methods used in PCD. The vestibular training task consists of locating and tracking a series of moving 3-dimensional balls presented at random within the participant's field of view.

Also known as: Vestibular rehabilitation therapy, Balance training, Vestibular training, Augmented reality

Real rTMS; Sham rTMS

SHAM repetitive transcranial magnetic stimulation DEVICE

Sham repetitive transcranial magnetic stimulation will be delivered using a Magstim Rapid 2 sham stimulator (Magstim, Whitland, UK) guided using neuronavigation (Brainsight, Rogue Research, Montreal, QC, Canada) to target primary motor cortex. Participants will receive 14 days of sham stimulation over a 3-week period. Stimulation will use a protocol called accelerated iTBS (Duprat et al., 2016) whereby sham iTBS will be delivered three times during the same study session. Each sham iTBS session will sound and feel identical to real iTBS delivery, but will not deliver a stimulating current. Sham iTBS sessions will each be separated by 15 minutes (Duprat et al., 2016; Wu et al., 2013). Sham stimulation will be delivered at 70% of the participant's resting motor threshold. Immediately following each 600-pulse period of sham iTBS, individuals will participate in 5 to 10 minutes of AR vestibular rehabilitation therapy.

Also known as: Sham intermittent theta burst stimulation

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18-65 years
• Diagnosis of mTBI according to the American Congress of Rehabilitation Medicine Diagnostic Criteria (Silverberg et al., 2023). All participants have diagnosis confirmed with Dr. Rathbone before enrollment.
• Persistent dizziness beyond 3-months following the initial head injury.
• Comprehension of spoken and written English language or have a language interpreter present for all study visits.

You may not qualify if:

• History of chronic dizziness unrelated to concussive events.
• Contraindications to TMS: presence of pacemaker, metal/electrical/magnetic implants not including titanium, known history of untreated or uncontrolled psychological disorders, pregnancy, history of seizure or diagnoses of epilepsy, taking medications that increase the risk of seizure.
• Inability to continue current medical therapies for the duration of the study.
• If imaging was done at the time of injury, individuals with a positive CT head will be excluded from the study

Sponsors & Collaborators

• McMaster University: lead
• Greenbank Concussion Clinic: collaborator

Study Sites (2)

Greenbank Concussion Clinic

Hamilton, Ontario, L8N 2B6, Canada

Location

McMaster University

Hamilton, Ontario, L8S 4L8, Canada

Location

Related Publications (33)

• Zhao X, Li Y, Tian Q, Zhu B, Zhao Z. Repetitive transcranial magnetic stimulation increases serum brain-derived neurotrophic factor and decreases interleukin-1beta and tumor necrosis factor-alpha in elderly patients with refractory depression. J Int Med Res. 2019 May;47(5):1848-1855. doi: 10.1177/0300060518817417. Epub 2019 Jan 7.

  PMID: 30616482 BACKGROUND

• Zuo C, Cao H, Feng F, Li G, Huang Y, Zhu L, Gu Z, Yang Y, Chen J, Jiang Y, Wang F. Repetitive transcranial magnetic stimulation exerts anti-inflammatory effects via modulating glial activation in mice with chronic unpredictable mild stress-induced depression. Int Immunopharmacol. 2022 Aug;109:108788. doi: 10.1016/j.intimp.2022.108788. Epub 2022 Apr 30.

  PMID: 35504201 BACKGROUND

• Velioglu HA, Hanoglu L, Bayraktaroglu Z, Toprak G, Guler EM, Bektay MY, Mutlu-Burnaz O, Yulug B. Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer's disease: Possible role of BDNF and oxidative stress. Neurobiol Learn Mem. 2021 Apr;180:107410. doi: 10.1016/j.nlm.2021.107410. Epub 2021 Feb 18.

  PMID: 33610772 BACKGROUND

• Rajkumar RP. Immune-inflammatory markers of response to repetitive transcranial magnetic stimulation in depression: A scoping review. Asian J Psychiatr. 2024 Jan;91:103852. doi: 10.1016/j.ajp.2023.103852. Epub 2023 Nov 29.

  PMID: 38070319 BACKGROUND

• Cha B, Kim J, Kim JM, Choi JW, Choi J, Kim K, Cha J, Kim M. Therapeutic Effect of Repetitive Transcranial Magnetic Stimulation for Post-stroke Vascular Cognitive Impairment: A Prospective Pilot Study. Front Neurol. 2022 Mar 22;13:813597. doi: 10.3389/fneur.2022.813597. eCollection 2022.

  PMID: 35392634 BACKGROUND

• Visser K, Koggel M, Blaauw J, van der Horn HJ, Jacobs B, van der Naalt J. Blood-based biomarkers of inflammation in mild traumatic brain injury: A systematic review. Neurosci Biobehav Rev. 2022 Jan;132:154-168. doi: 10.1016/j.neubiorev.2021.11.036. Epub 2021 Nov 23.

  PMID: 34826510 BACKGROUND

• Liao LY, Zhu Y, Peng QY, Gao Q, Liu L, Wang QH, Gao SH, Tao Y, Huang H, Xu PD, Gao CY. Intermittent Theta-Burst Stimulation for Stroke: Primary Motor Cortex Versus Cerebellar Stimulation: A Randomized Sham-Controlled Trial. Stroke. 2024 Jan;55(1):156-165. doi: 10.1161/STROKEAHA.123.044892. Epub 2023 Nov 30.

  PMID: 38037225 BACKGROUND

• Paxman E, Stilling J, Mercier L, Debert CT. Repetitive transcranial magnetic stimulation (rTMS) as a treatment for chronic dizziness following mild traumatic brain injury. BMJ Case Rep. 2018 Nov 5;2018:bcr2018226698. doi: 10.1136/bcr-2018-226698.

  PMID: 30396889 BACKGROUND

• Zhang JJ, Bai Z, Fong KNK. Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial. Stroke. 2022 Jul;53(7):2171-2181. doi: 10.1161/STROKEAHA.121.037870. Epub 2022 Mar 23.

  PMID: 35317611 BACKGROUND

• Platz T, Adler-Wiebe M, Roschka S, Lotze M. Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects. Restor Neurol Neurosci. 2018;36(1):117-130. doi: 10.3233/RNN-170774.

  PMID: 29439364 BACKGROUND

• Huang YZ, Sommer M, Thickbroom G, Hamada M, Pascual-Leonne A, Paulus W, Classen J, Peterchev AV, Zangen A, Ugawa Y. Consensus: New methodologies for brain stimulation. Brain Stimul. 2009 Jan;2(1):2-13. doi: 10.1016/j.brs.2008.09.007. Epub 2008 Oct 7.

  PMID: 20633398 BACKGROUND

• Szturm T, Betker AL, Moussavi Z, Desai A, Goodman V. Effects of an interactive computer game exercise regimen on balance impairment in frail community-dwelling older adults: a randomized controlled trial. Phys Ther. 2011 Oct;91(10):1449-62. doi: 10.2522/ptj.20090205. Epub 2011 Jul 28.

  PMID: 21799138 BACKGROUND

• Rosiak O, Krajewski K, Woszczak M, Jozefowicz-Korczynska M. Evaluation of the effectiveness of a Virtual Reality-based exercise program for Unilateral Peripheral Vestibular Deficit. J Vestib Res. 2018;28(5-6):409-415. doi: 10.3233/VES-180647.

  PMID: 30714985 BACKGROUND

• Smolka W, Smolka K, Markowski J, Pilch J, Piotrowska-Seweryn A, Zwierzchowska A. The efficacy of vestibular rehabilitation in patients with chronic unilateral vestibular dysfunction. Int J Occup Med Environ Health. 2020 Apr 30;33(3):273-282. doi: 10.13075/ijomeh.1896.01330. Epub 2020 Mar 26.

  PMID: 32235946 BACKGROUND

• Aligene K, Lin E. Vestibular and balance treatment of the concussed athlete. NeuroRehabilitation. 2013;32(3):543-53. doi: 10.3233/NRE-130876.

  PMID: 23648608 BACKGROUND

• Murray DA, Meldrum D, Lennon O. Can vestibular rehabilitation exercises help patients with concussion? A systematic review of efficacy, prescription and progression patterns. Br J Sports Med. 2017 Mar;51(5):442-451. doi: 10.1136/bjsports-2016-096081. Epub 2016 Sep 21.

  PMID: 27655831 BACKGROUND

• Broglio SP, Collins MW, Williams RM, Mucha A, Kontos AP. Current and emerging rehabilitation for concussion: a review of the evidence. Clin Sports Med. 2015 Apr;34(2):213-31. doi: 10.1016/j.csm.2014.12.005. Epub 2015 Jan 24.

  PMID: 25818710 BACKGROUND

• Toglia JU, Rosenberg PE, Ronis ML. Posttraumatic dizziness; vestibular, audiologic, and medicolegal aspects. Arch Otolaryngol. 1970 Nov;92(5):485-92. doi: 10.1001/archotol.1970.04310050067010. No abstract available.

  PMID: 5506059 BACKGROUND

• Hall CD, Herdman SJ, Whitney SL, Anson ER, Carender WJ, Hoppes CW, Cass SP, Christy JB, Cohen HS, Fife TD, Furman JM, Shepard NT, Clendaniel RA, Dishman JD, Goebel JA, Meldrum D, Ryan C, Wallace RL, Woodward NJ. Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From the Academy of Neurologic Physical Therapy of the American Physical Therapy Association. J Neurol Phys Ther. 2022 Apr 1;46(2):118-177. doi: 10.1097/NPT.0000000000000382.

  PMID: 34864777 BACKGROUND

• Ciorba A, Bianchini C, Scanelli G, Pala M, Zurlo A, Aimoni C. The impact of dizziness on quality-of-life in the elderly. Eur Arch Otorhinolaryngol. 2017 Mar;274(3):1245-1250. doi: 10.1007/s00405-016-4222-z. Epub 2016 Jul 22.

  PMID: 27450383 BACKGROUND

• Marshall S, Bayley M, McCullagh S, Velikonja D, Berrigan L, Ouchterlony D, Weegar K; mTBI Expert Consensus Group. Updated clinical practice guidelines for concussion/mild traumatic brain injury and persistent symptoms. Brain Inj. 2015;29(6):688-700. doi: 10.3109/02699052.2015.1004755. Epub 2015 Apr 14.

  PMID: 25871303 BACKGROUND

• Dougherty JM, Carney M, Hohman MH, Emmady PD. Vestibular Dysfunction. 2023 Jul 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK558926/

  PMID: 32644352 BACKGROUND

• Hartvigsen J, Boyle E, Cassidy JD, Carroll LJ. Mild traumatic brain injury after motor vehicle collisions: what are the symptoms and who treats them? A population-based 1-year inception cohort study. Arch Phys Med Rehabil. 2014 Mar;95(3 Suppl):S286-94. doi: 10.1016/j.apmr.2013.07.029.

  PMID: 24581914 BACKGROUND

• Corwin DJ, Wiebe DJ, Zonfrillo MR, Grady MF, Robinson RL, Goodman AM, Master CL. Vestibular Deficits following Youth Concussion. J Pediatr. 2015 May;166(5):1221-5. doi: 10.1016/j.jpeds.2015.01.039. Epub 2015 Mar 5.

  PMID: 25748568 BACKGROUND

• Gianoli GJ. Post-concussive Dizziness: A Review and Clinical Approach to the Patient. Front Neurol. 2022 Jan 4;12:718318. doi: 10.3389/fneur.2021.718318. eCollection 2021.

  PMID: 35058868 BACKGROUND

• Ryan LM, Warden DL. Post concussion syndrome. Int Rev Psychiatry. 2003 Nov;15(4):310-6. doi: 10.1080/09540260310001606692.

  PMID: 15276952 BACKGROUND

• Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, Kraus J, Coronado VG; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004 Feb;(43 Suppl):28-60. doi: 10.1080/16501960410023732.

  PMID: 15083870 BACKGROUND

• Duprat R, Desmyter S, Rudi de R, van Heeringen K, Van den Abbeele D, Tandt H, Bakic J, Pourtois G, Dedoncker J, Vervaet M, Van Autreve S, Lemmens GM, Baeken C. Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission? J Affect Disord. 2016 Aug;200:6-14. doi: 10.1016/j.jad.2016.04.015. Epub 2016 Apr 19.

  PMID: 27107779 BACKGROUND

• Hays RD, Spritzer KL, Schalet BD, Cella D. PROMIS(R)-29 v2.0 profile physical and mental health summary scores. Qual Life Res. 2018 Jul;27(7):1885-1891. doi: 10.1007/s11136-018-1842-3. Epub 2018 Mar 22.

  PMID: 29569016 BACKGROUND

• King NS, Crawford S, Wenden FJ, Moss NE, Wade DT. The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol. 1995 Sep;242(9):587-92. doi: 10.1007/BF00868811.

  PMID: 8551320 BACKGROUND

• Powell LE, Myers AM. The Activities-specific Balance Confidence (ABC) Scale. J Gerontol A Biol Sci Med Sci. 1995 Jan;50A(1):M28-34. doi: 10.1093/gerona/50a.1.m28.

  PMID: 7814786 BACKGROUND

• Bell DR, Guskiewicz KM, Clark MA, Padua DA. Systematic review of the balance error scoring system. Sports Health. 2011 May;3(3):287-95. doi: 10.1177/1941738111403122.

  PMID: 23016020 BACKGROUND

• Jacobson GP, Newman CW. The development of the Dizziness Handicap Inventory. Arch Otolaryngol Head Neck Surg. 1990 Apr;116(4):424-7. doi: 10.1001/archotol.1990.01870040046011.

  PMID: 2317323 BACKGROUND

MeSH Terms

Conditions

Brain Concussion; Vestibular Diseases; Dizziness

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Aimee J Nelson, PhD

CONTACT

9055259140; nelsonaj@mcmaster.ca

Daniel B Soppitt, BSc

CONTACT

9052463301; soppittd@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will be blinded to their intervention group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Aimee J. Nelson, PhD

Model Details: Participants will be split into two groups, one that will receive real rTMS and one that will receive sham rTMS.

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 16, 2024
• Study Start: January 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 13, 2025

Record last verified: 2024-12

Locations

CA (2)