Exercise Reset for Concussion in a Military Environment

NCT05498038 | Recruiting

• 1 other identifier: TP210003
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 2

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.

Conditions

Brain Concussion

Keywords

concussion; military; aerobic exercise; recovery; return to duty

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (20)

• Concentration of Salivary BDNF

  4 years

• Salivary miRNA

  4 years

• National Institute of Neurological Disorders Scale (NIHSS)

  4 years

• Stroke Patient Reported Outcomes and Measurement Information System (PROMIS) scale

  4 years

• The Health Care Climate Questionnaire (HCCQ)

  4 years

Study Arms (3)

Healthy Control Service Members

NO INTERVENTION

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.

Concussed Service Members PRA

NO INTERVENTION

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.

Concussed Service Members PRA+Exercise

EXPERIMENTAL

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

Interventions

Aerobic Exercise BEHAVIORAL

Participants are asked to complete at least 20 minutes of aerobic exercise every day, excluding clinic visits.

Concussed Service Members PRA+Exercise

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• State University of New York at Buffalo: lead
• Children's Hospital of Philadelphia: collaborator
• United States Department of Defense: collaborator
• University of Pennsylvania: collaborator
• University of North Carolina, Chapel Hill: collaborator
• The Geneva Foundation: collaborator
• Center for Neuroscience and Regenerative Medicine (CNRM): collaborator
• Axon Medical Technologies LLC: collaborator

Study Sites (2)

Fort Liberty

Fayetteville, North Carolina, 28310, United States

RECRUITING

Camp LeJeune

Jacksonville, North Carolina, 28547, United States

RECRUITING

MeSH Terms

Conditions

Brain Concussion

Interventions

Exercise

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• John Leddy, MD

  University at Buffalo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John J Leddy, MD

CONTACT

7162043200; leddy@buffalo.edu

Haley Chizuk, PhD, ATC

CONTACT

7162043200; haleychi@buffalo.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: John J Leddy, MD

Model Details: 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.

Study Record Dates

• First Submitted: August 9, 2022
• First Posted: August 11, 2022
• Study Start: August 7, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)