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

项目摘要 脑震荡被定义为导致急性神经功能障碍的轻度创伤性脑损伤。 最近的研究表明，脑震荡后有氧运动的强度低于症状加重的水平， 安全了然而，现有随机对照试验的临床益处表明有很大的改进空间。 此外，我们目前对神经生理学的基本变化的理解是不完整的， 运动治疗确定引起治疗效果所需的精确运动剂量（体积/强度） 脑震荡后的反应将导致增强和更精确的脑震荡后康复策略。 我们发表的数据和试点数据表明，轻微的脑震荡后运动与更快的症状有关 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，我们已经确定，最佳的运动量，以区分那些与/无脑震荡 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，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） 恢复脑血管调节，这些生理功能是可行的和可行的康复 目标的因此，使用前瞻性随机临床试验设计，我们的目的是确定是否高剂量运动>（150 分钟/周，个体化强度水平），导致：症状更快/更慢 消退、生理功能改变或继发性后遗症减少。我们的多学科调查 该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 和心理社会结果。因此，我们将招募、初步测试和随机分配13-18岁的青少年 脑震荡后≤10天进行高剂量有氧运动或标准治疗（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。我们将获得 每次访视时的脑血管功能和血清生物标志物数据，并量化运动、症状和 次生的连续的。首先，我们的目标是研究如何剂量（强度，持续时间和频率） 在脑震荡后10天内开始的有氧运动计划会影响症状消退的时间， 在青少年中的标准护理。第二，我们的目标是评估 有氧运动、神经炎症的生物标志物和脑血管功能。第三，我们的目标是阐明 脑震荡后高剂量运动如何影响持续继发性后遗症的发展（焦虑， 抑郁症，运动恐惧症，同伴关系，学术问题）。通过挑战目前公认的， 运动建议运动相关的脑震荡，我们将开辟新的领域，以改善 康复战略。

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.