Investigating Novel Treatments for Concussion: Impact of Compression Vest on Rehabilitation Outcomes

Study Overview
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Brief Summary
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The purpose of this investigation is to determine the effect of a weighted compression vest in addition to usual medical care and exercise rehabilitation on cardiovascular, neurocognitive, balance and anxiety measures in individuals medically diagnosed with, and being treated for, a mild traumatic brain injury.

Detailed Description
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Mild traumatic brain injury (mTBI), or concussion, induces significant impairment to a patient's mobility and tolerance for daily living activities with symptoms that include decreased balance, dizziness, confusion, headaches, visual and auditory sensitivities. If recognized promptly, many of these injuries respond well to immediate rest and standard rehabilitation strategies. However, approximately 10-30% of these patients will experience persistent symptoms beyond the  2 week period of spontaneous healing. The persistent symptoms point to neural damage, or disrupted neural networks in the brain, but the actual mechanism or nature of neural damage remains to be elucidated. The brain's neural activity must be supported by rapid adjustments to, and optimal distribution of, blood flow. However, cerebrovascular control remains poorly studied in the context of persistent concussion symptoms, particularly the reactivity element of flow control such as how fast it recovers during drops in blood pressure such as when one stands up from the sitting posture. Cerebrovascular damage in mTBI appears to affect mostly the autoregulatory adjustments to changes in brain perfusion pressure (i.e., from lying down to standing up) (Len et al., 2013;Junger et al., 1997). The investigators will study the impact of mTBI in both acute and persistent stages on cerebrovascular adjustments to metabolic and pressure-dependent stimuli. Currently, decisions regarding rate and completeness of healing remain subjective which can lead to earlier-than-optimal return of the patient to inappropriate levels of activity, work or school. Improved and cost-effective markers of the rate and completeness of brain healing are needed that can be obtained in the clinic. One challenge might be the emphasis in previous investigations on searching for a single biomarker of damage in a highly integrated system. Rather, the investigators believe it may be more effective to employ a holistic perspective; focusing on a comprehensive neural outcome might provide enhanced insight into the severity of damage and rate or completion of recovery. Previously, several investigators established heart rate variability (HRV) as sensitive marker of abnormal brain function in TBI (traumatic brain injury) cases for both adults and children (Goldstein et al., 1998;Goldstein et al., 1996). Moreover, these studies imply that autonomic nervous system control of heart rate is disrupted in proportion to the degree of neurologic insult. Thus, heart rate power spectral analysis may prove to be a useful adjunct in determining severity of neurologic injury and prognosis for recovery. Despite many studies outlining the relationship between mTBI and HRV (Ryan et al., 2011;Goldstein et al., 1998;Goldstein et al., 1996;Papaioannou et al., 2008;La Fountaine et al., 2009) no follow-up research has been conducted to establish this method (which is cost-effective, non-invasive, comprehensive and easily-obtained) as a routine assessment of TBI severity, or rehabilitative efficacy. An additional neural network associated with cardiac function is the baroreflex and the sensitivity of this neural network (baroreflex sensitivity; BRS) can be studied with non-invasive measures of heart rate and blood pressure. In the past and currently our lab has used both methods of HRV and BRS safely and effectively (Zamir et al., 2013;Kiviniemi et al., 2010;Kiviniemi et al., 2011;Shoemaker et al., 2012). This current study will assess the feasibility and impact of routine measurements of cardiac dynamics as a sensitive marker of the severity and persistence of overall brain damage in mTBI patients. Based on more than 30 failed clinical trials, no single pharmacological agent can be prescribed to minimize TBI-induced brain damage, despite efficacy shown for several agents in rodent studies (see (Kabadi & Faden, 2014) for review). In contrast, non-pharmacological approaches in rodents, show that both pathophysiological changes and neurological impairment after experimental TBI can be attenuated by physical activity (Griesbach et al., 2004;Griesbach et al., 2009). Thus, there is value in considering application of appropriate exercise as soon as possible in mTBI patients, but not too soon because the value of exercise in rodent models were observed only when applied after the acute stage (Griesbach et al., 2007;Piao et al., 2013). Therefore, this study will also examine the impact of adding prescriptive exercise in addition to usual clinical care on the rate of concussion recovery. Enabling patients to receive the benefits of enhanced levels of physical activity during treatments for concussion may be limited by the concussion symptoms. Nonetheless, recent anecdotal evidence from our Parkwood group has illustrated the remarkable benefit to many patients with persistent symptoms provided by the wearing of a compression vest (HSREB #103325 and #104865). Briefly, the weighted compression vests (5% of the individual's body mass) are individualized and fitted to each subject to ensure its snug but does not impede one's respirations (similar to a bulletproof vest). The noted benefits of the compression vest include instant improvements to balance and gait, and reduced anxiety during stair climbing. Since this adaptive method of treatment appears to exert a powerful effect on enhancing patient's ability to perform exercise, and is consistent with the personalized medicine approach (like the exercise intervention), further investigation into the effect of the compression vest on concussion symptoms and rehabilitation is a viable area of research. To date the impact of compression vest interventions has yet to be examined in patients during the acute TBI phase or in younger individuals. Thus, the aim of the next phase of study is to establish whether interventions with a weighted compression vest can enhance exercise tolerance for patients in both acute and persistent phases of the TBI, with explorations into possible mechanistic links to cerebrovascular, cardiovascular and neural outcomes. If so, then new evidence supporting the use of compression vests could change clinical practice and, importantly, improve long-term health outcomes for many patients. In review, the purpose of this investigation is to determine the efficacy of novel methods of mild traumatic brain injury rehabilitation in addition to usual concussion rehabilitation programs. Concussed participants will complete a longitudinal study in which they will be randomly allocated to one of three rehabilitation groups: 1) usual care 2) usual care + exercise 3) usual care + exercise + compression vest. The efficacy of each rehabilitation group will be primarily quantified via changes in routine cardiac dynamic measurements (HRV, BRS, changes in blood flow with changes in posture).

Official Title
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Investigating Novel Treatments for Concussion: Impact of Compression Vest on Rehabilitation Outcomes

Conditions
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Brain Concussion, Post-Concussion Syndrome

Intervention / Treatment
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* Device: London Health Sciences Centre - Compression Vest
* Other: exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: concussed: medically diagnosed with, and being treated for a concussion for no longer than 1 year healthy volunteer: no previous medical diagnosis of a concussion Exclusion Criteria: bone or muscle problems that could impact balance or how well you walk diagnosis of pre-existing heart disease medications that affect heart or blood vessel control pre-existing brain disorders such as Parkinson's, Multiple Sclerosis, Raynaud's, Multiple System Atrophy, metabolic disorders such as diabetes, a history of significant neck injury, or focal neurologic deficit primary or metastatic bone tumour severe osteoporosis if you are, or think you might be, pregnant or breastfeeding if you are not able to be understand English

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 40 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual care + exercise<br>Usual care + exercise | Other: exercise<br>* exercise<br>|
| No Intervention: No care, no exercise<br>No care, no exercise | |
| Experimental: Usual care + exercise + compression vest<br>Usual care + exercise + London Health Sciences Centre - Compression Vest | Device: London Health Sciences Centre - Compression Vest<br>* London Health Sciences Centre - Compression Vest<br>Other: exercise<br>* exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in symptom profile | Timeline to asymptomatic and clinical discharge | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline | 
| Change in exercise tolerance | Duration and wattage achieved at symptom exacerbation | baseline, four-weeks post-baseline, six-week post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety | Generalized Anxiety Disorder 7-item (GAD-7) scale | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline | 
| Balance | Change in Stability Index, quantified via BioDex Technology | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline | 
| Transcranial Doppler Ultrasound - Cerebrovascular Function | Change in middle cerebral artery blood velocity - cm/s | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline | 
| Heart Rate Variability | Measure of autonomic function - quantified via R-R interval duration (seconds) | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline | 
| Baroreflex Sensitivity | Measure of autonomic function - quantified via changes in blood pressure for a given heart rate | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline | 
| Cognitive Function | Cogingram - assessment of psychomotor function, attention, learning and working memory | baseline, two-weeks, three-weeks, four-weeks, 5-weeks and 6-weeks post-baseline |