StrokeNet I-ACQUIRE 12-month Follow-up Study

该竞争性修订申请是针对父母卒中网I-ACQUIRE III期试验（5U01NS106655- 02）提出的一项为期12个月的随访评估，该评估针对的是接受了两种剂量I-ACQUIRE（一种高强度儿童约束诱导运动疗法（CIMT））之一的婴幼儿。额外的数据将为160名围产期动脉缺血性卒中（PAIS）和偏瘫患儿（8 - 36个月大）的长期预后提供具有临床意义和可能新颖的见解。家长研究在治疗结束和6个月后获得治疗后评估。在I-ACQUIRE研究启动时没有新的证据，有力地说明了进行这一额外评估的理由。治疗结果的长期相关性的主题特别有趣和具有临床影响，因为上肢技能在生命的早期以戏剧性的方式发展。因此，可能存在由I-ACQUIRE治疗引起的重要功能变化，这些变化直到儿童长大后才完全表现出来。此外，幼儿的能力感可能会在一个月的强化i -习得治疗中发生深刻的变化；反过来，儿童、家庭和治疗临床医生可能会提高他们对未来成就的期望，并扩大儿童在家庭和社区参加各种适合年龄的活动的机会。我们提出了一个新的特定目标：评估接受I-ACQUIRE治疗的儿童的治疗结束和治疗后6个月的结果（在III期I-ACQUIRE研究中测量）在12个月的随访中是否保持稳定、改善或下降，以及是否在两个剂量组之间观察到差异模式。12个月随访评估包括上肢运动和功能技能（单侧和双侧）；大肌肉运动、语言、认知和社会情感发展的跨领域发展；儿童在典型年龄活动中的参与水平，通过包含一个新的，心理测量学上强大的标准化工具来衡量。所生成的前瞻性纵向数据集将提供前所未有的机会来描述考虑儿童临床特征、中枢神经系统和遗传生物标志物、治疗史和环境机会的发育轨迹。公共卫生影响：美国每年有3400多名婴儿患有PAIS，如果得不到有效治疗，很可能终身损害神经运动和认知功能。如果I-ACQUIRE被证明是有效的，特别是如果其益处甚至影响到后期的发育模式，那么该领域将有迫切需要的III期确证证据和补充的长期随访数据，这对改变这一弱势儿童群体的康复和改善临床结果至关重要。

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.