R01HD108133

Modulating Exercise Dosage to Improve Concussion Rehabilitation: A Randomized Clinical Trial - Project Summary

Concussions are defined as a mild form of traumatic brain injury that result in acute neurological dysfunction. Recent work suggests that post-concussion aerobic exercise at an intensity level below symptom exacerbation is safe. However, clinical benefits from existing randomized controlled trials indicate substantial room for improvement. Additionally, we currently have 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.

Our published and pilot data indicate that light post-concussion exercise was associated with faster symptom resolution time and less severe symptoms. However, we relied on self-reported data and observational designs. Furthermore, we 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, we 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 sequelae.

Our multidisciplinary investigative team has expertise investigating concussion, exercise physiology, fluid biomarkers, cerebrovascular physiology, and psychosocial outcomes. Thus, we will enroll, initially test, and randomize adolescents ages 13-18 years old =10 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. We will obtain cerebrovascular function and serum biomarker data at each visit, and quantify exercise, symptoms, and secondary sequelae continuously.

First, we 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, we aim to assess the mechanistic relationship between aerobic exercise, biomarkers of neuroinflammation, and cerebrovascular function. Third, we aim to elucidate how high dose exercise after concussion affects persistent secondary sequelae development (anxiety, depression, kinesiophobia, peer relationships, academic concerns).

By challenging the currently accepted exercise recommendations for sport-related concussion, we will break new ground toward improving rehabilitation strategies.

The Regents Of The University Of Colorado

THE EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENTS MISSION IS TO LEAD RESEARCH AND TRAINING TO UNDERSTAND HUMAN DEVELOPMENT, IMPROVE REPRODUCTIVE HEALTH, ENHANCE THE LIVES OF CHILDREN AND ADOLESCENTS, AND OPTIMIZE ABILITIES FOR ALL.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

Aurora, Colorado 800457106 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the total obligations have increased 398% from $662,706 to $3,302,557.