Addressing Sleep in Adolescents Post-concussion (“ASAP Study”): A Phase 2 Clinical Trial

项目摘要 在美国，每年有超过500,000名青少年遭受轻度创伤性脑损伤(又称“脑震荡”)。 尽管有“轻度”一词，但脑震荡症状会扰乱青少年机能的方方面面， 从学校到家庭的友谊，并损害了生活质量。尽管许多年轻人恢复得很快，但~三分之一的人仍然有 迟发性脑震荡症状(PPCS)在伤后一个月或以后出现。PPC很难用药物治疗， 因为脑震荡引起的病理生理学在1-3周内减弱。相反，现代治疗方法寻求 以有助于PPCS的可修改的患者行为为目标。越来越多的证据表明，睡眠不佳 质量或数量是PPCS的未得到充分解决的、强有力的、可治疗的贡献者，特别是对青少年而言。 事实上，最近的研究表明，有针对性的行为睡眠疗法可以改善青少年的睡眠和 其他持续性脑震荡后症状，但已发表的治疗方法需要4-6次治疗 会议在受伤后几个月进行。这样的方法对家庭来说既昂贵又繁重，不适合 综合护理模式，并使青年及其家人承受数月的长期保健计划负担。在……里面 相比之下，我们的团队开发了一种针对青少年的单节行为睡眠干预 设计为在急性病理生理减弱后不久(受伤后4-7周)分娩，以阻止 长期的症状负担。临床前和第一阶段研究表明，这种方法是可行的， 被接受，并有可能改善睡眠和其他PPC。我们的长期计划是测试 这一干预措施在应用环境中的有效性。为了证明和指导这一大规模试验，我们在这里 建议进行2期临床试验，在受控的情况下明确测试干预的效果。我们 将随机抽取70名12-18岁的青少年，他们正在经历PPCS，睡眠质量不佳或 受伤后4-7周接受一次睡眠治疗(TX)或照常护理(对照)的质量。 我们将在随机化之前评估睡眠、PPCS和真实世界的功能，然后再评估一周 1个月后。我们的主要目标是确定TX改善两种睡眠的短期疗效 和PPCS。其次，我们将评估TX的持续疗效及其对日常功能的影响。 我们还将探索潜在的影响因素(例如，人口统计学、伤害相关因素)。为了确保 这项研究的成功完成，我们已经组建了一支儿科脑损伤和 PPC、青少年睡眠研究、行为睡眠医学和生物统计学 成功的合作，包括类似的研究和我们的第一阶段试验。目前的研究代表了一个 我们研究计划的重要下一步，在开始之前在第二阶段试验中明确测试疗效 进行一项更大的(阶段3)应用效果研究。如果像我们提议的那样，我们的短暂干预既改善了 睡眠和减少其他PPC，这可能导致一个强大的新工具，以加速恢复和 每年减轻数十万青少年的负担。

Project Summary Over 500,000 adolescents sustain mild traumatic brain injuries (aka “concussions”) in the US each year. Despite the term “mild,” concussion symptoms disrupt all aspects of an adolescent’s functioning, from school to friendships to family, and impair quality of life. Although many youth recover quickly, ~1/3 still have protracted postconcussive symptoms (PPCS) a month or later post-injury. PPCS are hard to treat medically, as concussion-induced pathophysiology wanes within 1-3 weeks. Instead, contemporary treatments seek to target modifiable patient behaviors that contribute to PPCS. There is accumulating evidence that poor sleep quality or quantity are under-addressed, potent, treatable contributors to PPCS, particularly for adolescents. Indeed, recent studies suggest that targeted behavioral sleep treatments can improve adolescent sleep and other persistent post-concussive symptoms, but published approaches have required 4-6 treatment sessions delivered months post-injury. Such approaches are costly and onerous for families, fit poorly with integrated care models, and leave youth and their families to suffer months of protracted PPCS burden. In contrast, our team has developed a single-session behavioral sleep intervention for adolescents that is designed to be delivered soon after acute pathophysiology wanes (4-7 weeks post-injury) to head off protracted symptom burden. Preclinical and Phase 1 studies suggest that this approach is feasible, well- accepted, and has the potential to improve both sleep and other PPCS. Our long-term plan is to test the effectiveness of that intervention in an applied setting. To justify and guide that large-scale trial, here we propose a Phase 2 clinical trial to definitively test the efficacy of the intervention in a controlled context. We will randomize 70 adolescents aged 12-18 years who are experiencing PPCS and poor sleep quantity or quality to receive either a 1-session sleep treatment (Tx) or care-as-usual (control) 4-7 weeks post-injury. We will assess sleep, PPCS, and real-world functioning just prior to randomization and then again 1 week and 1 month later. Our primary aim is to determine the short-term efficacy of the Tx in improving both sleep and PPCS. Secondarily, we will assess the sustained efficacy of the Tx and its impact on daily functioning. We will also explore potential effect modifiers (e.g., demographics, injury-related factors). To ensure successful completion of this study, we have assembled a team of experts in pediatric brain injury and PPCS, adolescent sleep research, behavioral sleep medicine, and biostatistics with a proven record of successful collaboration, including on similar studies and our Phase 1 trial. The current study represents an important next step in our research program, definitively testing efficacy in a Phase 2 trial prior to embarking on a larger (Phase 3) applied effectiveness study. If, as we propose, our brief intervention both improves sleep and reduces other PPCS, this could lead to a powerful new tool to accelerate the recovery and alleviate burden for hundreds of thousands of adolescents every year.