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. We will conduct a prospective four-year multicenter mechanistic treatment (Phase 3) RCT in CSM of personalized sub-threshold aerobic exercise added to the PRA compared with the PRA alone. 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.
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 (BCMT) 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 (ANS) regulation in CSM. Hyp 3.2: Aerobic exercise improves expression of salivary brain-derived neurotrophic factor (BDNF), BDNF-related miRNAs, 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. Aim 4: Evaluate the suitability of the Exercise RESET testing and intervention approach for military use informed by study participants and providers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
168
Participants are asked to complete at least 20 minutes of aerobic exercise every day, excluding clinic visits.
Fort Liberty
Fayetteville, North Carolina, United States
RECRUITINGCamp LeJeune
Jacksonville, North Carolina, United States
RECRUITINGPersistent 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.
Time frame: 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.
Time frame: 3 months
Neurobehaviorial Symptom Inventory-22 (NSI)
To assess ongoing concussion symptoms, one of the main outcomes of the study. The NSI is a 5-minute measure validated in military populations to characterize concussion symptoms, endorsed by VA/DoD as a core TBI outcome measure. We will also use the symptom scale of the NSI to ask CSM about symptoms that existed before the concussion.
Time frame: 4 years
Average weekly Physical Activity time
Average of activity time per day over one week (hours:minutes) - Physical activity is measured using Polar Coach to control for this potential mediator of concussion recovery. Activity time in duration per day (hours:minutes) is tracked and then manually averaged and recorded via a standardized Excel spreadsheet.
Time frame: 4 years
Buffalo Concussion March-in-place Test (BCMT)
Average total steps per day over one week- Physical activity is measured using Polar Coach to control for this potential mediator of concussion recovery. Total steps per day are tracked and then manually averaged and recorded via a standardized Excel spreadsheet.
Time frame: 4 years
Daily Symptom Score Severity
Daily Symptom Score Severity will be measured using Ecological Momentary Assessment (EMA) (RECOUPS) - Measure daily symptoms to control for this potential mediator of concussion recovery. Participants report their symptom score once daily in response to text messages sent to their smartphone.
Time frame: 4 years
Average Nightly Sleep Quality
Measure sleep quality using Polar Coach to control for this potential mediator of concussion recovery. Duration of sleep time, sleep start time, sleep end time, and sleep restlessness score of each sleep session are tracked. Average sleep time per night, average sleep continuity, and average sleep continuity percentages are recorded via a standardized Excel spreadsheet and summated to generate a sleep quality score which will be analzyed.
Time frame: 4 years
Concentration of Salivary BDNF
Concentration of salivary BDNF will be collected and used as a measure to assess enhanced neuroplasticity as a possible mechanism for the effect of aerobic exercise treatment on concussion.
Time frame: 4 years
Salivary miRNA
Concentration of salivary miRNA will be collected and used as a measure to assess enhanced neuroplasticity as a possible mechanism for the effect of aerobic exercise treatment on concussion.
Time frame: 4 years
National Institute of Neurological Disorders Scale (NIHSS)
We will collect brief validated measures of anxiety and depression to assess improved mental health as a potential mechanism for the effect of aerobic exercise treatment on concussion. Low scores indicate no deficit in neurological symptoms; high scores indicate severe deficits in neurological symptoms, and values range from 0 to 42.
Time frame: 4 years
Stroke Patient Reported Outcomes and Measurement Information System (PROMIS) scale
We will collect brief validated measures of anxiety and depression to assess improved mental health as a potential mechanism for the effect of aerobic exercise treatment on concussion. Higher scores compared to the general population via standardized T-Scores indicate impairments, and values range from 20 to 80.
Time frame: 4 years
The Health Care Climate Questionnaire (HCCQ)
We will collect brief validated health care related measures that follow Self - Determination Theory. The HCCQ measures the degree an individual feels autonomy-supported or controlled within the healthcare context, with higher scores indicating more autonomy and support felt. The range of scores is 15 to 105.
Time frame: 4 years
PTSD- Military Checklist (PCL-M)
We will collect brief validated health care related measures that follow Self - Determination Theory. The PCL-M measures the degree an individual exhibits PTSD symptoms, with higher scores indicating higher likelihood of PTSD. The range of scores is from 17 to 85.
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Time frame: 4 years
Brief Resilience Survey (BRS)
We will measure resilience using this scale, which has been used to evaluate the effect on concussion recovery after sport- related concussion. Higher scores indicate more resilience, and scores range from 6 to 30.
Time frame: 4 years
Army Command Climate Survey
We will use this scale to measure morale. Higher scores indicate higher feelings of morale in units, and scores range from 2 to 10.
Time frame: 4 years
Cervical Range of Motion
Cervical Range of Motion (ROM) in degrees will be measured using the NeckCare device, an electronic medical device worn on the head to provide reliable assessments. Range of values is based on individual ability, with lower values indicating less ROM and higher values indicating more ROM.
Time frame: 4 years
Joint Position Error (JPE)
Joint Position Error (JPE) in degrees will be measured using the NeckCare device, an electronic medical device worn on the head to provide reliable assessments. Range of values is based on individual ability, with lower values indicating more precise proprioceptive capabilities, and higher values indicating less precise proprioceptive capabilities.
Time frame: 4 years
The Butterfly Test
Movement sense and eye-head-neck coordination using a score to control values will be measured using the NeckCare device, an electronic medical device work on the head to provide reliable assessments. Range of values is based on individual abilities compared to standard values, with lower values indicating more precise proprioceptive capabilities, and higher values indicating less precise proprioceptive capabilities.
Time frame: 4 years
Heart Rate Variability (HRV) milliseconds
HRV, measured as R-R intervals in ms, will be measured using the Elite HRV app 5 minutes pre-post exercise. This will be used to assess parasympathetic autonomic function as a possible mechanism for the beneficial effect of aerobic exercise treatment.
Time frame: 4 years
The rate of HR recovery after the BCMT in beats per minute (BPM)
The difference in HR from the immediate cessation of exercise to two minutes post-exercise will be used to assess parasympathetic autonomic function as a possible mechanism for the beneficial effect of aerobic exercise treatment.
Time frame: 4 years
Pupillary reaction time
Pupillary reaction (time in milliseconds) will be assessed using the Intellig-eyes system. This will be used to assess parasympathetic autonomic function as a possible mechanism for the beneficial effect of aerobic exercise treatment.
Time frame: 4 years
Pupil diameter change
Pupil diameter change will be measured in mm assessed using the Intellig-eyes system. This will be used to assess parasympathetic autonomic function as a possible mechanism for the beneficial effect of aerobic exercise treatment.
Time frame: 4 years
Convergence rate millseconds
Convergence rate (in ms) will be assessed using the Intellig-eyes system. This will be used to assess parasympathetic autonomic function as a possible mechanism for the beneficial effect of aerobic exercise treatment.
Time frame: 4 years
Time of Completion wioth the King Devick (KD) pre and post-exercise
We will use the KD test to assess for exercise-induced vision dysfunction (EIVD). Higher time (in seconds) indicates more dysfucntion indicative of concussion.
Time frame: 4 years
Number of errors on the King Devick (KD) pre and post-exercise
We will use the KD test to assess for exercise-induced vision dysfunction (EIVD). Higher number of errors indicates more dysfunction indicative of concussion.
Time frame: 4 years
Run/roll/aim task
We will use the run/roll/aim task to assess symptom change pre and post high demand vestibular activity.
Time frame: 4 years
Suitability of Exercise RESET
Study participants who complete test procedures will be invited to participate in a semi-structured interview with the intention to learn about how the intervention worked or did not work for and to get feedback about how the intervention might be improved for implementation in a military environment. On site providers who engage in concussion care will also be invited for a separate semi-structured interview to provide insights on the acceptability of the Buffalo Protocol in the military health care setting.
Time frame: 4 years