An interventional study of Repetitive transcranial magnetic stimulation and Augmented reality vestibular rehabilitation therapy in Mild Traumatic Brain Injury, Concussion, Chronic Dizziness and Vestibular Problem, sponsored by McMaster University. Not yet recruiting at 2 sites in Canada. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-01-13.
Sponsored by McMaster University · Not applicable, Interventional, and Treatment
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:
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.
The incidence of traumatic brain injury (TBI) is increasing in Canada, and it is expected to be one of the most common neurological conditions affecting Canadians by 2031. Up to 90% of TBIs are classified as mild (m)TBI, also known as concussion. A federal concussion report from 2019 indicated an annual prevalence of 200,000 mTBIs in Canada. Symptoms of mTBI, termed post-concussion symptoms (PCS), include dizziness, headache, alterations in mood, and cognitive impairment. PCS generally resolves on its own. However, some patients experience persistent PCS lasting beyond 3 months after the initial head injury.
Dizziness is the second most common symptom of mTBI after headache. It is estimated that up to 81% of mTBI patients will present with dizziness upon initial clinical examination, which may continue to persist beyond 1-year following the initial trauma in 25% of patients. Post-concussion dizziness (PCD) can present as postural instability, ongoing vertigo, balance impairments, nausea, and intolerance to head motion. These symptoms can drastically reduce quality of life and impact the ability to drive, work, and perform daily activities.
PCD is typically associated with vestibular impairment. Further, many patients complaining of dizziness following mTBI demonstrate physiologic abnormalities with the auditory and vestibular systems. Consequently, the most preferable treatment for PCD is a form of balance training called vestibular rehabilitation therapy (VRT). VRT consists of a set of exercises which promote adaptation, substitution, and habituation of the vestibular system. Adaptation, mediated by neuroplasticity, is the gradual remodelling of the nervous system as it "adapts" to the signals from the damaged vestibular system. Substitution is the process of learning strategies to compensate for poor vestibular function. Habituation is the gradual desensitization to certain movements through repeated exposure to those movements. These exercises are often individually prescribed based on personal areas of disability. Specific exercise types include gaze stability, habituation, substitution, and balance exercises. These target deficits in the vestibulo-ocular reflex (VOR), improve impaired motion sensitivity, facilitate central reprogramming, and improve balance. Traditional VRT, such as a balance task, is monotonous and often requires trained professionals to administer. VRT, in the form of interactive games, however, is engaging and has been shown to affect balance, dizziness, and mobility positively. A form of sensorimotor training consisting of an interactive game presented through augmented reality (AR) has not yet been explored. It may serve to reduce PCD by similar mechanisms as the aforementioned VRTs.
AR is typically presented through opaque glasses, which overlay virtual objects onto the user's environment. Users can then interact with both the virtual and physical environments simultaneously. Our AR intervention involves a game that promotes goal-directed movements of the head to accomplish tasks in various head orientations and postural positions. Through repeated exposure, this game aims to facilitate adaptation, substitution, and habituation of the vestibular system to reduce PCD.
A non-invasive neuromodulation technique called repetitive transcranial magnetic stimulation (rTMS) may improve AR vestibular training. One form of rTMS delivery called intermittent theta burst stimulation (iTBS) promotes synaptic plasticity by inducing long term potentiation (LTP)-like changes in neuronal excitability. Literature suggests that iTBS delivered to the primary motor cortex (M1) may improve learning in conjunction with motor training. rTMS may also improve dizziness. Ten sessions of rTMS reduce dizziness symptom severity and frequency by more than 50% in patients suffering from severe PCD. iTBS delivered to M1 improves balance in post-stroke patients. Systemic inflammation is an important physiological response to mTBI that may contribute to dizziness. Several studies have observed the anti-inflammatory effects of rTMS in clinical populations such as stroke and depression. Zhao et al. found that 20 sessions of rTMS on patients with refractory depression reduced elevated levels of TNF-⍺ and IL-1β to that of healthy controls. Levels of BDNF, which is important for brain growth, increased to that of healthy controls following the intervention. This effect on TNF-⍺, IL-1β, and BDNF was not observed in the clinical control group who did not receive rTMS. Cha et al. reported a similar reduction in inflammatory cytokines TNF-⍺, IL-1β, and IL-6 after 10 sessions of rTMS in post-stroke patients. Velioglu et al. found that 10 sessions of rTMS increased BDNF in patients with Alzheimer's disease. These effects also provide evidence towards a possible mechanism behind the effect of rTMS on other persistent PCS.
Patients with severe persistent PCD often require medical or surgical intervention. There is a clear need for non-invasive treatment options for these individuals. The primary objective of this study is to determine if the proposed technique is feasible and can be used to alter concussion symptoms in patients with PCD in a larger study. This study will also explore the effects of iTBS in combination with AR vestibular training on dizziness disability and postural stability in patients with PCD. Additionally, this research aims to determine if rTMS can modulate inflammation in persistent PCS.
637 studies on the registry are indexed under Brain Concussion; 163 are open to participants now.
This study's planned enrollment of 40 is below the median of 63 across 446 interventional studies indexed under Brain Concussion.
Browse Brain Concussion studies →McMaster University is the lead sponsor of 741 studies on the registry; 127 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.
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Behavioral: Augmented reality vestibular rehabilitation therapy · Device: SHAM repetitive transcranial magnetic stimulation
Device: Repetitive transcranial magnetic stimulation · Behavioral: Augmented reality vestibular rehabilitation therapy
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
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
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
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.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Balance Error Scoring System (BESS)
The BESS is an objective and quantitative measure used to assess postural stability deficits in mTBI. The assessment will take place on a force plate (BTrackS; balancetrackingsystems.com) in order to measure the participant's center of gravity and sway. The BESS consists of 3 eyes-closed stances: feet together with hands on the hips, single-leg stance on nondominant foot with hands on the hips, and tandem stance with nondominant foot behind the dominant foot. The dominant foot will be identified by determining which foot is used to kick a ball. Each stance is performed on a stable surface (hard floor) and an unstable surface (foam pad) with the eyes closed for 20-seconds per trial. Errors are counted during each trial. BESS results will be reported as a score from 0 to 60, with higher scores representing greater deficits in postural stability (worse outcome).
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Activities-Specific Balance Confidence (ABC) Scale
This questionnaire will be used to evaluate participants' balance confidence. An average of balance confidence as it relates to 16 specific everyday activities will be reported from 0% (no confidence) to 100% (complete confidence).
Time frame: 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)
This questionnaire will assess the presence and severity of a wide range of post-concussion symptoms.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
PROMIS-29
This questionnaire will assess six domains of health (physical function, anxiety, depression, fatigue, sleep disturbance, social activities) as they relate to participants' dizziness. Questions under the headings "Pain Intensity" and "Pain Interference" will be omitted from this questionnaire as they do not relate to the population.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Motor evoked potential (MEP)
This measure will be used to assess changes in corticospinal excitability. To obtain MEP, thirty individual pulses of TMS at 120% RMT will be applied over the motor hotspot of the dominant hand FDI muscle.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Cytokines (IL-1ß, IL-6, TNF-⍺, IL-10)
A blood sample will be used to evaluate changes in serum concentrations (pg/mL) of cytokines IL-1ß, IL-6, TNF-⍺, IL-10.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
C-reactive protein
A blood sample will be used to evaluate changes in serum C-reactive protein concentrations (µg/mL).
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Monocyte chemoattractant protein-1
A blood sample will be used to evaluate changes in serum concentrations (pg/mL) of monocyte chemoattractant protein-1.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Brain-derived neurotrophic factor
A blood sample will be used to evaluate changes in serum concentrations (ng/mL) of brain-derived neurotrophic factor.
Time frame: At baseline (before the first intervention session) and post-intervention (following the final intervention session)
Start is estimated for Jan 2025; primary completion for Dec 2025, 11 months later.
Of 248 non-industry interventional studies with no phase under Brain Concussion, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 47. This study's planned 11 months is below that.
Counting every sponsor, half of 264 studies reached it within 28 months; a quarter within 19 and three quarters within 47.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.
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