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.

项目概要 脑震荡被定义为一种轻微的创伤性脑损伤，会导致急性神经功能障碍。 最近的研究表明，脑震荡后进行强度水平低于症状恶化的有氧运动是有效的。 然而，现有随机对照试验的临床益处表明仍有很大的改进空间。 此外，我们目前对响应神经生理学变化的不完全了解 确定引起治疗所需的精确运动剂量（运动量/强度）。 脑震荡后的反应将导致脑震荡后康复策略的增强和更精确。 我们发布的试验数据表明，轻微的脑震荡后运动与更快的症状相关 解决时间和不太严重的症状，但我们依赖于自我报告的数据和观察设计。 此外，我们还确定了区分有/无脑震荡患者的最佳运动量 一个月后的症状每周 >160 分钟，高于规定的标准运动量 （>100 分钟/周），并符合心血管健康的现有建议（>150 分钟/周）。 除此之外，考虑到定期适度运动对减少炎症的积极作用（例如白细胞介素 6） 并恢复脑血管调节，这些生理功能代表了可行的康复 因此，通过前瞻性随机临床试验设计，我们的目标是确定高剂量运动是否>（150） 分钟/周（个性化强度水平），相对于标准护理，导致： 更快/更慢的症状 分辨率，改变生理功能，或减少继发性后遗症。 团队拥有研究脑震荡、运动生理学、液体生物标志物、脑血管生理学的专业知识， 因此，我们将招募 13-18 岁的青少年，对其进行初步测试和随机分组。 脑震荡后 10 天以内进行高剂量有氧运动或标准护理（症状有限，自我指导 体力活动），并在症状缓解后和症状缓解后 8 周重新评估。 每次访视时记录脑血管功能和血清生物标志物数据，并量化运动、症状和 首先，我们的目的是检查持续发生继发性后遗症的剂量（强度、持续时间和频率）。 脑震荡后 10 天内开始的有氧运动计划会影响症状消退的时间，相对 其次，我们的目标是评估青少年之间的机制关系。 第三，我们的目的是阐明有氧运动、神经炎症的生物标志物和脑血管功能。 脑震荡后大剂量运动如何影响继发性后遗症的持续发展（焦虑、 抑郁症、运动恐惧症、同伴关系、学术问题）。 针对运动相关脑震荡的锻炼建议，我们将在改善方面开辟新天地 康复策略。