Exercise Reset for Concussion in a Military Environment

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

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Concussion
• Intervention / Treatment: Behavioral: 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.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: John J Leddy, MD; Phone Number: 7162043200; Email: leddy@buffalo.edu
• Study Contact Backup: Name: Haley Chizuk, PhD, ATC; Phone Number: 2043 7162043200; Email: haleychi@buffalo.edu

Study Locations

• United States
  • North Carolina
    • Fayetteville, North Carolina, United States, 28310
      • Recruiting
      • Fort Liberty
      • Contact: Kaleigh Presgraves
    • Jacksonville, North Carolina, United States, 28547
      • Recruiting
      • Camp LeJeune
      • Contact: Robert Carlson, MPT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Exclusion Criteria (Providers):

• Not active duty
• Not currently an active clinician (MD, DO, PT, ATC, OT) involved in concussion management
• Only involved in concussion management at emergent timepoint
• Unwilling to participate
• Unable to be contacted by telephone or Zoom

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy Control Service Members; 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. All HC participants will be provided with an activity monitor (with GPS tracking disabled) to wear 24 hours/day for measurement of daily physical activity and sleep duration over the time between first and final test sessions. The activity monitor also acts as an HR monitor to record the participants' HR during their prescribed exercise bouts. HC will be asked to exercise each day at approximately 70% of their age-predicted maximum heart rate (from the formula 220 minus age x 0.7 = target HR) for 20 minutes to control for the effect of exercise on the physiological tests.
No Intervention: Concussed Service Members PRA; CSM randomized to PRA alone will receive written instructions on how to follow the PRA protocol. All participants will be provided with an activity monitor (with GPS tracking disabled), and we will record daily physical activity and sleep patterns.
Experimental: Concussed Service Members PRA+Exercise; CSM randomized to aerobic exercise+PRA will receive their individualized aerobic exercise prescription plus written instructions on how to follow the PRA protocol. CSM will start the exercise program the day after the first visit. All participants will be reminded each day by text message to complete their assigned activity (in the case of exercise + PRA participants, to perform their exercise at the prescribed dose [HR]) and to report any adverse effects). All participants will also report symptoms once daily in response to a text message to their phone. All participants will wear an activity monitor continuously until clinical recovery or for 4 weeks to measure daily activity and sleep. The activity monitor will also act as an HR monitor and will be worn by participants in the PRA+aerobic exercise group during daily exercise sessions to measure participant adherence to the prescribed exercise dose.	Behavioral: Aerobic Exercise; Participants are asked to complete at least 20 minutes of aerobic exercise every day, excluding clinic visits.

What is the study measuring?

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
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.	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.	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.	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.	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.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	4 years

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: Children's Hospital of Philadelphia; University of Pennsylvania; United States Department of Defense; University of North Carolina, Chapel Hill; The Geneva Foundation; Center for Neuroscience and Regenerative Medicine (CNRM); Axon Medical Technologies LLC
• Investigators: Principal Investigator: John Leddy, MD, University at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: recovery; aerobic exercise; military; concussion; return to duty
• Additional Relevant MeSH Terms: Brain Injuries, Traumatic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Brain Concussion; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: TP210003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No