Perinatal Arterial Stroke (PAS): A Phase III Multi-site Trial of I-ACQUIRE

we propose a Phase III randomized trial in which I-ACQUIRE will be administered to infants with PAS (8 – 24 mos old) by protocol-trained therapists in sessions of either 3 or 6 hrs per day, 5 days/week for 4 weeks. Treatment is in a homelike or natural setting where operant conditioning techniques are applied to achieve goals paced for each infant. I-ACQUIRE is designed to be enjoyable and varied as new skills are first elicited and then shaped through successive approximations to achieve treatment goals. Treatment activities include self-help, object play, social interactions, and physical activities. I-ACQUIRE includes the core features of constraint-induced movement therapy (CIMT)16-18 supplemented with a parent training component, bilateral limb therapy activities, and emphasis on total body skills. Fidelity of treatment is monitored weekly with corrective action if protocol deviations occur. Clinical Trial Design: 240 infants will be randomly assigned to receive one of the following 3 treatments for 4 weeks: 1) Moderate dose I-ACQUIRE (3 hrs/day, 5 days/wk), 2) High dose I-ACQUIRE (6 hrs/day, 5 days/wk), or 3) Usual and Customary Treatment (U&CT). Community therapists who will document dosage and treatment approaches will provide U&CT. Blinded assessments using standardized tools appropriate for this clinical infant population will occur at baseline, end of treatment, and 6 mos post-treatment. Parents, community therapists, and pediatric neurologists will provide supplemental data about infant behavior, treatment responses, and neurological status. Additionally, parents from each site will serve as active research partners throughout the trial, including representation on the Steering Committee, thus supporting the NIH and IOM goal of increasing patient and key stakeholder engagement in clinical trials.19,20 The overarching goal is to evaluate the efficacy of I-ACQUIRE for treating infants with PAS.