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: 10412780
• 负责人: David R. Howell
• 金额: $ 66.27万
• 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/10412780
• 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 Clinical Trials; 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; TimeLine; Traumatic Brain Injury; Traumatic injury; Visit; Work; base; 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; rehabilitation strategy; response; standard of care; 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.

项目摘要 脑震荡被定义为一种轻度的脑损伤形式，导致急性神经功能障碍。 最近的工作表明，在症状加剧的强度水平上，脑震荡后有氧运动是 安全的。然而，现有的随机对照试验的临床益处表明改善了很大的空间。 此外，我们目前对响应的神经生理学的理解不完全 运动治疗。确定引起治疗所需的精确运动剂量（体积/强度） 咨询后的反应将导致增强，更精确的脑后康复策略。 我们已发布的试点数据，表明脑后运动的轻度症状与症状更快有关 解决时间和不太严重的症状，但我们放弃了自我报告的数据和观察设计。 此外，我们已经确定，在没有/没有咨询的情况下区分那些的最佳运动量 一个月后的症状> 160分钟/周，高于规定的标准运动量 （> 100分钟/周），并符合现有的心血管健康建议（> 150分钟/周）。 除此之外，鉴于规则中度运动的积极影响减少炎症（例如，白介素6） 并恢复脑血管调节，这些生理功能代表可行且可行的康复 目标。这是使用前瞻性随机临床试验设计的，我们旨在确定是否高剂量运动>（150 相对于护理标准的个性强度水平的分钟/周，导致：更快/较慢的症状 分辨率，身体功能改变或次级序列降低。我们的多学科调查 团队有专业知识调查咨询，运动生理学，流体生物标志物，脑血管生理学， 和社会心理成果。这就是我们将注册，最初测试和随机分配13-18岁的青少年 高剂量有氧运动或护理标准后脑后≤10天（症状有限，自我引入 体育锻炼），并在症状缓解症状和8周后重新评估症状解决方案。我们将获得 每次访问时脑血管功能和血清生物标志物数据，并量化练习，符号和 次生序列继续。首先，我们旨在研究如何剂量（强度，持续时间和频率） 咨询后10天内启动的有氧运动计划会影响符号分辨率，相对的时间 在青少年中获得标准的护理。其次，我们旨在评估 有氧运动，神经炎症的生物标志物和脑血管功能。第三，我们旨在阐明 脑震荡后的高剂量运动会影响持续的继发性序列发育（焦虑， 抑郁症，运动恐惧症，同伴关系，学术问题）。通过挑战当前接受的 与运动相关咨询的锻炼建议，我们将为改进的新基础奠定基础 康复策略。