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

调节运动量以改善脑震荡康复：一项随机临床试验

• 批准号: 10616746
• 负责人: David R. Howell
• 金额: $ 67.8万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616746
• 关键词: 18 year old; Acute; Adolescent; Aerobic Exercise; Affect; Age; Anxiety; Biological Markers; Brain Concussion; Cerebrovascular Physiology; Childhood; Clinical; Clinical Trials Design; Collaborations; Critical Illness; Data; Data Reporting; Development; Dose; Enrollment; Exercise; Exercise Physiology; Frequencies; Functional disorder; Guidelines; Hour; Impairment; Inflammation; Inflammatory; Injury; Instruction; Interleukin-6; Intervention Trial; Light; Link; Liquid substance; Mediating; Mental Depression; Moderate Exercise; National Institute of Child Health and Human Development; Nature; Neurologic Dysfunctions; Observational Study; Outcome; Patient Self-Report; Patients; Physical activity; Physiological; Physiology; Publishing; Randomized; Randomized, Controlled Trials; Recommendation; Recording of previous events; Recovery; Regulation; Rehabilitation therapy; Reporting; Research; Research Priority; Resolution; Rest; Secondary Prevention; Serum; Severities; Site; Sports; Symptoms; Testing; Therapeutic Effect; Time; Traumatic Brain Injury; Traumatic injury; Visit; Work; cardiovascular health; cerebrovascular; concussive symptom; design; dosage; effective therapy; exercise intensity; exercise prescription; exercise program; experience; global health; high standard; improved; interdisciplinary approach; multidisciplinary; neuroinflammation; neurophysiology; optimal treatments; pediatric trauma; peer; precision medicine; prevent; prospective; psychosocial; randomized, clinical trials; rehabilitation strategy; response; standard of care; timeline; treatment response

Project Summary 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, 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 light post-concussion exercise was associated with faster symptom resolution time and less severe symptoms, yet 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 sequalae. 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 sequalae 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 sequalae 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.

项目总结