Brain Concussion
Conditions
Keywords
concussion, military, aerobic exercise, recovery, return to duty
Brief summary
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.
Detailed description
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.
Interventions
BEHAVIORALAerobic Exercise
Participants are asked to complete at least 20 minutes of aerobic exercise every day, excluding clinic visits.
Sponsors
State University of New York at Buffalo
United States Department of Defense
Children's Hospital of Philadelphia
University of Pennsylvania
University of North Carolina, Chapel Hill
The Geneva Foundation
Center for Neuroscience and Regenerative Medicine (CNRM)
Axon Medical Technologies LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
(Participants): For the CSM Group: * Active-duty service member * Aged 18-40 years * Injury occurred within 9 days of injury * Diagnosed with concussion by an experienced clinician using standard international criteria For the HC Group: * Active-duty service member * Ages 18-40
Exclusion criteria
(Participants): For the CSM group: * 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 * Active substance abuse/dependence * Unwillingness to perform intervention * Limited English proficiency * Confirmed pregnancy For the HC group: * Has lingering symptoms from a previous concussion or has recovered from a concussion less than 1-month ago * On a limited profile or "chit" for light duty * Active substance abuse/dependence * Unwilling to perform intervention * Limited English proficiency * Confirmed pregnancy Inclusion Criteria (Providers): * Active duty * Currently active clinician (MD, DO, PT, ATC, OT) involved in concussion management beyond initial emergent diagnosis * Willing to participate * Able to be contacted by telephone or Zoom
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Symptom Score Severity | 4 years | 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. |
| Average Nightly Sleep Quality | 4 years | 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. |
| Persistent Post Concussive Symptoms (PPCS) (Yes/No) | 28 days | 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. |
| Days until Recovery | 3 months | 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. |
| Neurobehaviorial Symptom Inventory-22 (NSI) | 4 years | 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. |
| Average weekly Physical Activity time | 4 years | 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. |
| Buffalo Concussion March-in-place Test (BCMT) | 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Army Command Climate Survey | 4 years | We will use this scale to measure morale. Higher scores indicate higher feelings of morale in units, and scores range from 2 to 10. |
| Cervical Range of Motion | 4 years | 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. |
| Joint Position Error (JPE) | 4 years | 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. |
| The Butterfly Test | 4 years | 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. |
| Heart Rate Variability (HRV) milliseconds | 4 years | 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. |
| The rate of HR recovery after the BCMT in beats per minute (BPM) | 4 years | 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. |
| Pupillary reaction time | 4 years | 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. |
| Pupil diameter change | 4 years | 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. |
| Convergence rate millseconds | 4 years | 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 of Completion wioth the King Devick (KD) pre and post-exercise | 4 years | We will use the KD test to assess for exercise-induced vision dysfunction (EIVD). Higher time (in seconds) indicates more dysfucntion indicative of concussion. |
| Number of errors on the King Devick (KD) pre and post-exercise | 4 years | We will use the KD test to assess for exercise-induced vision dysfunction (EIVD). Higher number of errors indicates more dysfunction indicative of concussion. |
| Run/roll/aim task | 4 years | We will use the run/roll/aim task to assess symptom change pre and post high demand vestibular activity. |
| Stroke Patient Reported Outcomes and Measurement Information System (PROMIS) scale | 4 years | 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. |
| Suitability of Exercise RESET | 4 years | 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. |
| Concentration of Salivary BDNF | 4 years | 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. |
| Salivary miRNA | 4 years | 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. |
| National Institute of Neurological Disorders Scale (NIHSS) | 4 years | 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. |
| The Health Care Climate Questionnaire (HCCQ) | 4 years | 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. |
| PTSD- Military Checklist (PCL-M) | 4 years | 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. |
| Brief Resilience Survey (BRS) | 4 years | 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. |
Countries
United States
Contacts
CONTACTJohn J Leddy, MD
CONTACTHaley Chizuk, PhD, ATC
PRINCIPAL_INVESTIGATORJohn Leddy, MD
University at Buffalo
Outcome results
None listed