Clinical trial NCT05498038: Exercise Reset for Concussion in a Military Environment
Official title: Exercise Reset for Concussion- Modifying the Buffalo Concussion Protocol for Application in a Military Environment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Brain Concussion
Keywords: aerobic exercise
military
service member*
concussion management
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Children's Hospital of Philadelphia
name: University of Pennsylvania
name: University of North Carolina, Chapel Hill
name: The Geneva Foundation
name: Center for Neuroscience and Regenerative Medicine (CNRM)
name: Axon Medical Technologies LLC
First posted: 2022-08-11
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Persistent Post Concussive Symptoms (PPCS) (Yes/No)
timeFrame: 28 days
measure: Days until Recovery
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Fort Liberty
state: North Carolina
city: Jacksonville
country: United States
facility: Camp LeJeune
state: North Carolina
Study officials:
affiliation: University at Buffalo
name: John Leddy, MD
role: PRINCIPAL_INVESTIGATOR
References: