Modulating Exercise Dosage to Improve Concussion Recovery

NCT ID: NCT05434130

Last Updated: 2024-09-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-05
• Study Completion Date: 2027-02-01

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.

Conditions

Concussion, Brain; Treatment; Aerobic Exercise; Inflammation; Depression, Anxiety

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

High Dose Exercise

The investigators will provide exercise dose recommendations for initial visit until symptom resolution, and revise upon symptom resolution (to use for the subsequent 8 weeks). These include intensity (target HR) and volume (frequency/duration). Intensity is calculated as 90% of the HR at the end of the exercise test. The volume recommendation is 150 mins/week (\~30 min/day; 5 days/week). The mode of exercise is another consideration. This will be left to participant preference, so that the investigators do not exclude potential participants due to lack of access to specific exercise equipment.

Group Type: EXPERIMENTAL

High Dose Exercise

Intervention Type: BEHAVIORAL

The investigators will initially test and randomize adolescents ages 13-18 years old ≤14 days post-concussion to high dose aerobic exercise (\>150 min/week, individualized intensity level) or standard-of-care (symptom limited, self-guided physical activity), and re-test upon symptom resolution and 8-weeks post symptom resolution

Standard-of-care

Participants are instructed to perform activity in line with physician recommendations. This consists of a general recommendation (no specific HR/volume) or symptom limited physical activity.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

High Dose Exercise

The investigators will initially test and randomize adolescents ages 13-18 years old ≤14 days post-concussion to high dose aerobic exercise (\>150 min/week, individualized intensity level) or standard-of-care (symptom limited, self-guided physical activity), and re-test upon symptom resolution and 8-weeks post symptom resolution

Intervention Type: BEHAVIORAL

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)

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

Spaulding Rehabilitation Hospital

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David R Howell, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado Denver | Anschutz

Locations

University of Colorado Denver

Aurora, Colorado, United States

Site Status: RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Spaulding Rehabilitation Hospital

Cambridge, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

David R Howell, PhD

Role: CONTACT

ConcussionResearch@cuanschutz.edu

7207771502

Kelsie Richardson, MS

Role: CONTACT

ConcussionResearch@cuanschutz.edu

7207771502

Facility Contacts

David R Howell, PhD

Role: primary

ConcussionResearch@cuanschutz.edu

7207771502

Kelsie Richardson, MS

Role: backup

ConcussionResearch@cuanschutz.edu

7207771502

Danielle Hunt, MS

Role: primary

William P Meehan III, MD

Role: backup

Andrew Taylor, PhD

Role: primary

J Andrew Taylor, PhD

Role: backup

Other Identifiers

R01HD108133

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-4932

Identifier Type: -

Identifier Source: org_study_id