Research Project
10305452
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.
