Multisite RCT of 3 Neurorehabilitation Therapies for Infants with Asymmetrical CP

描述（由申请人提供）：脑瘫（CP）是儿童神经运动障碍中最常见的一类，导致生产力和健康的终身损害，以及高昂的费用。迄今为止，没有一种形式的婴儿疗法通过足够有力的随机对照试验证明是有效的；此外，常规疗法往往不能产生有临床意义的益处。这项修订后的应用建立在两项独立初步研究的新发现的基础上，这些研究表明，接受替代形式的约束诱导运动疗法（CIMT）对婴儿有益。采用多位点随机对照试验设计，72名患有单侧或不对称CP的婴儿（6 - 18岁）将被随机分配接受3种手动形式的多组分治疗之一。主要结果包括客观评估（基线，治疗后1周，6个月和12个月）单侧和双侧活动中受影响的上肢（UE）技能，以及基于新的婴儿fNIRS方案的脑侧化变化。具体目标是：1)比较3种有前景的婴儿cimt形式的效果，这些形式在剂量（3小时/天X 21天）和关键治疗元素（塑形，大规模练习，家庭为基础，嵌入游戏和日常活动，由训练有素的治疗师与父母合作提供）上相同，但在使用约束方面有所不同-连续石膏，兼职夹板，或无约束；2)与无约束相比，评估与约束条件（连续或兼职）相关的应力水平和安全性。将使用来自婴儿和父母的多种唾液皮质醇样本、父母自我报告和观察来评估压力。安全监测将包括活动范围、皮肤完整性、感觉意识、铸造手臂和手的功能使用，以及涉及铸造侧的侧度评分的变化。尽管先前的研究证实了对婴儿使用约束的一般安全性和可接受性，但关于其潜在的益处和风险，存在强烈的竞争假设。影响：如果一种或多种被测试的婴儿疗法在12个月后产生巨大的益处，那么这些发现将对未来的临床实践产生重大影响。此外，对于单侧和不对称CP的儿童，在生命早期进行高效的治疗可能会导致更高水平的独立性、学习、社会参与和生活质量。

DESCRIPTION (provided by applicant): Cerebral palsy (CP) is the most common class of childhood neuromotor disabilities, resulting in lifelong impairments in productivity and health as well as high costs. To date, no form of infant therapy has proven efficacious via an adequately powered RCT; further, usual and customary therapies often fail to produce clinically meaningful benefits. This revised application builds on new findings from 2 independent preliminary studies showing benefits for infants who received alternative forms of constraint-induced movement therapy (CIMT). Using a multisite RCT design, 72 infants (6 - 18 mos old) with unilateral or asymmetrical CP will be randomly assigned to receive one of 3 manualized forms of multi-component therapies. Primary outcomes include objective assessments (at baseline then 1 wk, 6 mos, and 12 mos post-therapy) of affected upper extremity (UE) skills in unilateral and bilateral activities, as well as changes in brain lateralization based on a novel fNIRS protocol fo infants. The specific aims are: 1) to compare the effects of 3 promising forms of Infant-CIMT that are identical in dosage (3 hr/day X 21 days) and their key therapy elements (shaping, massed practice, home-based, embedded in play and everyday activities, provided by a trained therapist in partnership with parents) but that differ in their use of constraint - continuous casting, part-time splint, or no constraint; and 2) to assess stress levels and safety related to constraint condition (continuous or part-time) compared to no constraint. Stress will be assessed using multiple salivary cortisol samples from infants and parents, parent self-report, and observations. Safety monitoring will include range of motion, skin integrity, sensory awareness, functional use of the casted arm and hand, as well as changes in laterality scores involving the casted side. Even though prior studies affirm the general safety and acceptability of using constraint with infants, there are strongly competing hypotheses about its potential benefits versus risks. Impact: if one or more of the tested infant therapies produces large magnitude benefits lasting up to 12 mos later, then these findings would have a high impact on future clinical practice. Moreover, highly effective therapy very early in life may lead to much higher levels of independence, learning, social engagement, and quality of life for children with unilateral and asymmetrical CP.