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50万青少年遭受轻度创伤性脑损伤（又名“脑震荡”）。 尽管有"轻度"的说法，脑震荡症状会破坏青少年功能的各个方面， 从学校到友谊再到家庭，并损害生活质量。虽然许多年轻人恢复得很快，但仍有1/3的人 持续性脑震荡后症状（PPCS）在受伤后一个月或更晚。PPCS在医学上很难治疗， 因为脑震荡引起的病理生理学在1 - 3周内减弱。相反，现代治疗方法试图 目标是有助于PPCS的可修改的患者行为。越来越多的证据表明睡眠不好 质量或数量是PPCS的未充分解决的、有效的、可治疗的因素，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治疗可以改善青少年的睡眠， 其他持续性脑震荡后症状，但已发表的方法需要4 - 6次治疗 在受伤后几个月进行治疗。这些方法对家庭来说是昂贵和繁重的， 综合护理模式，使青年及其家庭遭受长达数月的PPCS负担。在 相比之下，我们的团队已经为青少年开发了一种单次行为睡眠干预， 设计在急性病理生理学减弱（损伤后4 - 7周）后立即交付， 长期症状负担。临床前和1期研究表明，这种方法是可行的，以及- 接受，并有可能改善睡眠和其他PPCS。我们的长期计划是测试 这种干预在实际环境中的有效性。为了证明和指导这一大规模试验，我们在这里 提出一项2期临床试验，以明确测试在受控环境中干预的有效性。我们 将随机选择70名12 - 18岁的青少年，他们正在经历PPCS和睡眠质量差，或 在受伤后4 - 7周接受1次睡眠治疗（Tx）或常规护理（对照）。 我们将在随机化前评估睡眠、PPCS和真实世界功能，然后再评估1周 一个月后。我们的主要目的是确定Tx在改善睡眠和睡眠方面的短期疗效。 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效果修饰符（例如，人口统计学、伤害相关因素）。确保 成功完成这项研究后，我们组建了一个儿科脑损伤专家团队， PPCS，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1期试验。目前的研究表明， 我们研究计划的下一步重要步骤是，在开始之前在2期试验中明确测试疗效 一项更大规模（3期）的应用有效性研究。如果像我们提议的那样，我们的简短干预 睡眠和减少其他PPCS，这可能会导致一个强大的新工具，以加速恢复， 每年为数十万青少年减负。

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.