Multisite RCT of 3 Neurorehabilitation Therapies for Infants with Asymmetrical CP

描述（由申请人提供）：脑瘫（CP）是最常见的儿童神经运动障碍，导致终身生产力和健康受损以及高昂的费用。迄今为止，没有任何形式的婴儿治疗通过充分把握度的RCT证明有效;此外，常规和常规治疗通常无法产生有临床意义的获益。这一修订后的应用程序建立在两项独立的初步研究的新发现的基础上，这些研究表明，接受其他形式的约束诱导运动疗法（CIMT）的婴儿受益。采用多中心RCT设计，将72名单侧或不对称CP婴儿（6 - 18月龄）随机分配接受3种手动形式的多组分治疗之一。主要结局包括对单侧和双侧活动中受影响上肢（UE）技能的客观评估（基线时，然后是治疗后1周、6个月和12个月），以及基于婴儿新fNIRS方案的大脑侧化变化。具体目标是：1）比较3种有前途的婴儿CIMT形式的效果，这些形式的剂量相同（3小时/天× 21天）及其关键治疗要素（塑形、集体练习、以家庭为基础、嵌入游戏和日常活动中，由训练有素的治疗师与父母合作提供），但在使用约束方面有所不同-连续铸造、兼职夹板或无约束;以及2）与无约束相比，评估与约束条件（连续或部分时间）相关的应力水平和安全性。将使用来自婴儿和父母的多个唾液皮质醇样本、父母自我报告和观察来评估压力。安全性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性使用，以及涉及铸造侧的偏侧性评分的变化。尽管先前的研究肯定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与风险，存在着强烈的竞争性假设。影响：如果一种或多种测试的婴儿疗法产生持续长达12个月的大幅度益处，则这些发现将对未来的临床实践具有高度影响。此外，在生命早期进行高效治疗可能会使单侧和不对称CP儿童的独立性、学习、社会参与和生活质量更高。

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.