Clinical trial NCT05434130: Modulating Exercise Dosage to Improve Concussion Recovery
Official title: Modulating Exercise Dosage to Improve Concussion Recovery: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Concussion, Brain
Treatment
Aerobic Exercise
Inflammation
Depression, Anxiety
Keywords: intervention
mild traumatic brain injury
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: Spaulding Rehabilitation Hospital
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-06-27
Enrollment: 216
Sex: ALL
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will use a block stratified RCT design. Our stratum factors are the biological variable of sex and recruitment location
Primary purpose: TREATMENT

Brief summary: Aerobic exercise has emerged as an effective treatment to reduce sport-related concussion symptom severity, yet existing work lacks rigor regarding the precise exercise volume and intensity required to elicit therapeutic effects, how exercise can alter concussion-related pathophysiology, and whether exercise can prevent the development of secondary sequelae. Our objective is to examine if a high dose exercise program (higher volume than currently prescribed at an individualized, safe intensity level) initiated within 14 days of concussion results in faster symptom resolution, altered physiological function, or reduced secondary sequalae. Findings from this research will lead to more rigorous and precise rehabilitation guidelines and improved understanding about how exercise affects neurophysiological function among adolescents with concussion.

Detailed description: Concussions are defined as a mild form of traumatic brain injury that result in acute neurological dysfunction. Recent work suggests post-concussion aerobic exercise at an intensity level below symptom exacerbation is safe. Yet, clinical benefits from existing randomized controlled trials indicate substantial room for improvement. Also, there is currently an incomplete understanding of the neurophysiology underlying changes in response to exercise treatment. Identifying the precise exercise dose (volume/intensity) required to elicit a therapeutic response following concussion will lead to enhanced and more precise post-concussion rehabilitation strategies. Published and pilot data by the investigators indicate light post-concussion exercise was associated with faster symptom resolution time and less severe symptoms, yet this relied on self-reported data and observational designs. Furthermore, the investigators have identified that the optimal exercise volume to differentiate those with/without concussion symptoms after one month was \>160 minutes/week, which is higher than standard exercise volumes prescribed (\>100 minutes/week), and in line with existing recommendations for cardiovascular health (\>150 minutes/week). Beyond this, given the positive effects of regular moderate exercise to reduce inflammation (e.g., interleukin 6) and restore cerebrovascular regulation, these physiological functions represent viable and feasible rehabilitation targets. Thus, using a prospective randomized clinical trial design, the investigators aim to identify if high dose exercise \>(150 minutes/week at an individualized intensity level), relative to standard-of-care, results in: faster/slower symptom resolution, altered physiological function, or reduced secondary sequalae. Our multidisciplinary investigative team has expertise investigating concussion, exercise physiology, fluid biomarkers, cerebrovascular physiology, and psychosocial outcomes. Thus, the investigators will enroll, initially test, and randomize adolescents ages 13-18 years old ≤14 days post-concussion to high dose aerobic exercise or standard-of-care (symptom limited, self-guided physical activity), and reassess upon symptom resolution and 8-weeks post symptom resolution. The investigators will obtain cerebrovascular function and serum biomarker data at each visit, and quantify exercise, symptoms, and secondary sequalae continuously. First, The investigators aim to examine how the dose (intensity, duration, and frequency) of an aerobic exercise program initiated within 10 days of concussion affects time to symptom resolution, relative to standard-of-care, among adolescents. Second, the investigators aim to assess the mechanistic relationship between aerobic exercise, biomarkers of neuroinflammation, and cerebrovascular function. Third, the investigators aim to elucidate how high dose exercise after concussion affects persistent secondary sequalae development (anxiety, depression, kinesiophobia, peer relationships, academic concerns). By challenging the currently accepted, exercise recommendations for sport-related concussion, the investigators will break new ground toward improving rehabilitation strategies.

Eligibility criteria: Inclusion Criteria:

* 13-18 years of age
* Post-Concussion Symptom Scale (PCSS) score \>10 to ensure participants are not recovered by enrollment
* Concussion diagnosis by a sports medicine physician

Exclusion Criteria:

* Pre-existing neurological disorders
* Exercise contraindications
* Concussion \<6 months before enrollment (excluding the current injury)

Primary outcomes:
measure: Time from injury to symptom resolution
timeFrame: From time of injury until defined symptom resolution observed, about 30 days
measure: Serum biomarker concentration: GFAP change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Anxiety and depression severity change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
Secondary outcomes:
measure: Serum biomarker concentration: IL-6 change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Serum biomarker concentration: TNF-alpha change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Serum biomarker concentration: IL1-RA change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Serum biomarker concentration: VEGF change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Serum biomarker concentration: MMP-9 change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Cerebral autoregulation
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Cerebral vasoreactivity change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Kinesiophobia severity change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Peer relationship attitudes change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
measure: Academic concerns change
timeFrame: Baseline, Visit 2 (scheduled after symptoms resolve, about 35 days post-baseline)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Cambridge
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
Study officials:
affiliation: University of Colorado Denver | Anschutz
name: David R Howell, PhD
role: PRINCIPAL_INVESTIGATOR
References: