StrokeNet I-ACQUIRE 12-month Follow-up Study

这项针对Parent Stroke Net I-Acquire阶段III试验的竞争性修订申请(5U01NS106655-02)建议对接受I-Acquire两种剂量之一的婴幼儿进行为期12个月的随访评估，I-Acquire是一种高强度儿科强制诱导运动疗法(CIMT)。这些额外的数据将为160名患有围产期动脉缺血性中风(PAIS)和偏瘫的儿童(治疗时为8-36个月)的长期结果提供具有临床意义和可能的新见解。母研究在治疗结束时和6个月后进行治疗后评估。I-Acquire研究启动时没有新的证据，这有力地说明了进行这项额外评估的理由。治疗结果的长期相关性这一主题特别耐人寻味，具有临床影响力，因为上肢技能在整个生命的早期都以戏剧性的方式发展。因此，I-Acquide治疗可能会引起重要的功能变化，直到儿童长大后才能完全显现出来。此外，幼儿的能力意识可能会因儿童在强化I-Acquire治疗一个月中的进步而发生深刻的变化；反过来，儿童、家庭和治疗临床医生可能会增加他们对未来成就的期望，并扩大儿童参与家庭和社区各种适龄活动的机会。我们提出了一个新的具体目标：评估接受I-Acquire治疗的儿童在治疗结束和治疗后6个月的结果(在第三阶段I-Acquire研究中衡量)在12个月的随访中是否保持稳定、改善或下降，以及两个剂量组之间是否存在差异模式。为期12个月的跟踪评估包括上肢运动和功能技能(单侧和双侧)；粗大运动、语言、认知和社会情感发展的跨领域发展；以及儿童参与典型年龄活动的水平，通过纳入一种新的、心理测量学强大的标准化工具来衡量。生成的前瞻性纵向数据集将提供一个前所未有的机会来描述发展轨迹，考虑到儿童的临床特征、中枢神经系统和遗传生物标记物、治疗历史和环境机会。公共卫生影响：在美国，每年有3400多名婴儿患有PAI，如果得不到有效的治疗，他们很有可能终身受损，神经运动和认知功能经常受损。如果I-Acquire被证明是有效的，特别是如果这些益处似乎影响到后来的发育模式，那么该领域将拥有急需的第三阶段确证证据和补充的长期跟踪数据，这些数据对于改变康复和改善这一脆弱的儿科人口的临床结果非常重要。

This Competing Revision application to the parent Stroke Net I-ACQUIRE Phase III Trial (5U01NS106655- 02) proposes a 12-month follow-up assessment for infants and toddlers who received one of two dosages of I- ACQUIRE – a form of high-intensity pediatric Constraint-Induced Movement Therapy (CIMT). The additional data will provide clinically meaningful and likely novel insights into longer-term outcomes for 160 children (8 - 36 months old when treated) with Perinatal Arterial Ischemic Stroke (PAIS) and hemiparesis. The parent study obtains post-treatment assessments at end-of-treatment and 6 months later. The rationale for this additional assessment is strongly informed by new evidence not available when the I-ACQUIRE Study was launched. The topic of longer-term correlates of treatment outcomes is especially intriguing and clinically impactful because upper extremity skills develop in dramatic ways throughout the early years of life. Accordingly, there may be important functional changes induced by the I-ACQUIRE treatment that are not fully manifest until children are older. Further, a young child's sense of competency may be profoundly changed by the child's progress during the month of intensive I-ACQUIRE treatment; in turn, the child, the family, and treating clinicians may increase their expectations for future achievement and expand the opportunities for the child to participate in a wide array of age-appropriate activities at home and in the community. We propose one new specific aim: To assess whether the end-of-treatment and 6-month post-treatment outcomes (measured in the Phase III I-ACQUIRE Study) for children treated with I-ACQUIRE remain stable, improve, or decline at 12-months follow-up and whether there is a differential pattern observed between the two dosage groups. The 12-month follow-up assessment includes upper extremity movement and functional skills (unilateral and bilateral); cross-domain development in gross motor, language, cognition, and socioemotional development; and children's participation levels in age-typical activities, measured by the inclusion of a new, psychometrically strong standardized tool. The prospective longitudinal dataset generated will afford an unprecedented opportunity to describe developmental trajectories considering children's clinical characteristics, CNS and genetic biomarkers, treatment histories, and environmental opportunities. Public Health Impact: Each year, 3400+ infants in the U.S. have PAIS with high likelihood of lifelong impairment in neuromotor and often cognitive functioning if not treated effectively. If I-ACQUIRE proves efficacious, and particularly if the benefits appear to influence even later developmental patterns, then the field will have the critically needed Phase III confirmatory evidence and the supplemental longer-term follow-up data important to transform rehabilitation and improve clinical outcomes for this vulnerable pediatric population.