Stephanie C. DeLuca, Ph.D. - US grants

DESCRIPTION (provided by applicant): Unilateral (hemiparetic) cerebral palsy (CP) affects an estimated 229,000 individuals in the U.S., with CP rates increasing in young children. Most traditional forms of therapy have proven ineffective, although they remain in widespread use. Two major research reviews (cf. Huang et al, 2010; Sakzewski et al, 2009) conclude that pediatric constraint-induced movement therapy (CIMT) is one of the most promising new therapies, despite wide variation in and vigorous debate about its key features. Two urgent, unresolved issues concern the effects associated with (a) different dosage levels of pediatric CIMT and (b) different types and duration of constraint. The proposed study is a multi-site, randomized controlled trial (RCT) of 144 children (3 - 6 yrs old) with hemiparetic CP. The multiple baseline 2 X 2 RCT study design will compare the effects of 2 dosage levels (3.0 hrs/day for 21 days versus 1.5 hrs/day for 21 days) under 2 distinct constraint conditions (Full-time cast versus Part-time splint). Children will first be studied in a control condition, receivin their usual therapy over 3 months, and then crossover to be randomly assigned to one of 4 CIMT treatment groups: (1) 3.0 hrs/day dosage, Full-time cast; (2) 3.0 hrs/day, Part-time splint; (3) 1.5 hrs/day, Full-time cast; and (4) 1.5 hrs/day, Part-time splint. For all groups, parents wil receive systematic training to help practice and extend their children's new and improved upper extremity skills. Children will be followed 3 months post-treatment. Children's neuromotor competence will be assessed via a comprehensive battery of standardized and innovative tools, administered 5 times over 8 months by individuals blinded to the subjects' control and treatment conditions. The primary outcome measures are the Assisted Hand Assessment (AHA), the Pediatric Motor Activity Log (PMAL), and the modified QUEST. Independent scoring of videotaped sessions and parent reports will supplement lab assessments, along with data transmitted from accelerometers. Specific Aim 1 focuses on comparing the effects of 2 dosage levels of pediatric CIMT. Specific Aim 2 compares the effects of 2 forms and duration of constraint, selected because of competing hypotheses about their impact on children and cortical re-organization. Specific Aim 3 uses clinical diagnostic and baseline data about subjects' individual differences to explore hypotheses about differential response to CIMT, including their levels of engagement during treatment, the types and magnitude of short- and longer-term changes detected, and whether other changes are documented beyond the realm of neuromotor competence (i.e., spillover effects). The results of this study will advance the development of rigorous, evidence-based standards for the practice of CIMT, with the potential for large-scale implementation to produce major benefits for children with CP. PUBLIC HEALTH RELEVANCE: This application seeks to conduct the first multi-site, randomized controlled trial (RCT) of a promising form of pediatric constraint-induced movement therapy (CIMT) for 3 - 6 yr old children with unilateral cerebral palsy. The RCT (N=144) will test the efficacy of 2 different dosage levels and 2 types of and duration of casting, compared to a control condition (usual treatment). The study findings are critically needed to establish evidence-based practice standards to improve lifelong neuromotor capacity for >229,000 affected individuals in the U.S.

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.

Project Summary (Didactic Interactions) Didactic Interactions are an integral core component of the proposed National Pediatric Rehabilitation Resource Center (PedRehab Ctr). We plan to offer a wide mix of didactic activities to assist others in the following areas: i) developing, rigorously testing, and appropriately measuring outcomes of new pediatric rehabilitation treatments via a variety of research designs; ii) analyzing multivariate and longitudinal data from pediatric clinical trials that face unique challenges, because children are developing at varying rates over the course of rehabilitation treatment and throughout the follow-up period; iii) developing and applying tools to measure Fidelity of Treatment Implementation; and iv) designing and conducting research in the relatively new field of Implementation Science, so that efficacious treatments can be applied in a timely and effective way in real world settings to realize maximum benefits. These Didactic Interactions offerings will be designed to be practically useful for scientists and clinicians interested in furthering clinical pediatric rehabilitation research. We plan to be responsive to the informational needs identified by the research community, clinicians, and parent and advocacy groups. A high priority will be engaging investigators from historically underrepresented groups in science. The specific aims for Didactic Interactions are: 1) to conduct multiple informative and inviting presentations ? including short courses, symposia, demonstration workshops, roundtable discussions, and Webinars - at a wide range of national and international professional meetings and venues each year. Over 5 years, we propose delivering a minimum of 30 events, targeted to investigators in pediatric neurology, developmental pediatrics, physical medicine and rehabilitation (physiatry), neonatology, general pediatrics, occupational therapy, physical therapy, child development, neuroscience, and biostatistics, as well as to parent/advocacy groups interested in rehabilitation research; 2) to link our major didactic presentations (specific aim 1 above) with timely follow-up activities appropriate to the content of the presentation, the target audience, and the potential for supporting longer-term collaborations and helping to developing promising pilot study applications; 3) to use our new PedRehab Ctr Website to archive the Didactic Interactions offerings along with supportive reference materials; and 4) to pursue opportunities to coordinate with others, including the other P2C Medical Rehabilitation Resource Centers, our CTSAs, national organizations, NIH special workshops, and StrokeNet, so that we actively share relevant materials and work synergistically to minimize duplication of effort and to maximize dissemination of high-quality, relevant didactic materials.