Exercise Reset for Concussion in a Military Environment

Study Overview
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Brief Summary
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Our primary objective is to show that early, personalized aerobic exercise treatment safely improves concussion recovery, speeds RTD, and reduces persistent symptoms in CSM. Our secondary objectives include demonstrating the clinical utility of our March-in-place test and determining fundamental mechanisms for the effect of exercise rehabilitation on concussion recovery.

Detailed Description
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Aim 1: Determine whether early sub-threshold aerobic exercise (i.e., light limited duty added to the current Department of Defense Progressive Return to Activity [DoD PRA]) protocol speeds return to duty (RTD), improves clinical recovery, and protects against risk of persistent post-concussive symptoms(PPCS). Hyp 1.1: Aerobic exercise+DoD PRA early after injury speeds RTD and improves clinical recovery in CSM compared to the DoD PRA protocol alone. Hyp 1.2: Early aerobic exercise+DoD PRA protects against risk of PPCS in concussed service members (CSM) at 1 and at 3 months post-injury versus the DoD PRA protocol alone. Aim 2: Determine whether a march-in-place test informs clinical decision-making and contributes to RTD decisions. Hyp 2.1: The degree of early exercise intolerance on the Buffalo Concussion March Test will correlate with the development of PPCS and inform clinician decision making on RTD. Aim 3: Determine how aerobic exercise improves concussion recovery. Hyp 3.1: Aerobic exercise improves abnormal autonomic nervous system regulation in CSM. Hyp 3.2: Aerobic exercise reverses changes in salivary brain-derived neurotrophic factor (BDNF), BDNF-related micro RNAs, and inflammatory-related miRNAs seen in CSM. Hyp 3.3: Aerobic exercise improves mental health (i.e., anxiety/depressive symptoms, sleep, resilience, self-efficacy, morale) in CSM.

Official Title
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Exercise Reset for Concussion- Modifying the Buffalo Concussion Protocol for Application in a Military Environment

Conditions
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Brain Concussion

Intervention / Treatment
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* Behavioral: Aerobic Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-40 years, Within 9 days of injury Diagnosed with concussion by an experienced clinician using standard international criteria Exclusion Criteria: Moderate or severe TBI as indicated by a GCS score <13, lesion on CT/MRI, and/or focal neurologic sign consistent with intracerebral lesion Injury involving loss of consciousness for >30 minutes or post-traumatic amnesia >24 hours Inability to exercise because of lower-extremity orthopedic injury, clinically significant vestibular or visual dysfunction, or increased cardiac risk Pre-existing conditions that prevent participation in active testing and/or rehabilitation History of more than 3 diagnosed concussions Currently on medications that affect autonomic function, such as ADHD medication or mood stabilizers Active substance abuse/dependence Unwillingness to perform intervention Limited English proficiency.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: This is a four-year multicenter mechanistic treatment (Phase 3) RCT that recruits CSM and healthy service members as controls. CSM who have signed a consent form to participate in the trial will be randomly assigned to either exercise+PRA or to PRA alone by the research assistant using a computer-generated randomization scheme generated by the study statistician. CSM will be allocated to trial arm using a pre-determined block randomization procedure in a 1:1 ratio, in multiples of 3 and limited to a maximum of 9, to reduce potential for imbalance across study arms. We will stratify the sample by sex and site and attempt to recruit a M:F ratio similar to the military in general (80:20). Randomization will occur without knowledge of the clinician who diagnosed the concussion. Data is collected at the first visit and weekly until clinical recovery, or up to 4 weeks from injury, and at the final 3 month time point. Controls will complete the clinic visits twice, two weeks apart.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy Control Service Members<br>Non-concussed, age-matched SM will serve as a healthy control group (HC) for comparing CSM to normal physiology and to control for the effect of time and of aerobic exercise. They will not be given intervention. | |
| No Intervention: Concussed Service Members PRA<br>CSM allocated to this group will complete PRA protocols/ will receive treatment as usual. | |
| Experimental: Concussed Service Members PRA+Exercise<br>CSM allocated to this group will complete PRA protocols/ will receive treatment as usual and will receive an exercise program in addition to PRA. | Behavioral: Aerobic Exercise<br>* Participants are asked to complete at least 20 minutes of aerobic exercise every day, excluding clinic visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent Post Concussive Symptoms (PPCS) (Yes/No) | PPCS is defined as recovery more than 28 days from the day of concussive injury (yes) or before 28 days (no). Recovery is defined as return to baseline symptoms, exercise tolerant and confirmation by independent medical examination. | 28 days | 
| Days until Recovery | Determination of clinical recovery will be made by a clinician. Each week we will use a multi-modal assessment to establish clinical recovery, which is defined as return to a pre-injury level of symptoms, a normal physical examination and exercise tolerant on the graded exercise assessment. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aerobic exercise, military, service member*, concussion management