Perinatal Arterial Stroke: A Multi-site RCT of Intensive Infant Rehabilitation (I-ACQUIRE)

Study Overview
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Brief Summary
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This is a Phase III clinical trial to compare the efficacy of two dosages of a new infant rehabilitation protocol - I-ACQUIRE - to usual and customary forms of infant rehabilitation in infants who experienced Perinatal Arterial Stroke (PAS).

Detailed Description
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The proposed study is a Phase III trial powered to determine efficacy of two different doses of I-ACQUIRE for children 8 to 36 months old with PAS and hemiparesis. The design is a prospective Randomized Controlled Trial (RCT) in which 240 children will be randomly assigned to one of 3 treatment groups (N=80 per group): 1) Moderate Dose I-ACQUIRE (3 hrs/day, 5 day/wk X 4 wks), 2) High Dose I-ACQUIRE (6hrs/day, 5 days/wk X 4 wks), or 3) Usual and Customary Treatment (U&CT). I-ACQUIRE will be delivered by protocol-trained therapists and monitored weekly for dosage and treatment fidelity; U&CT will be provided by community therapists with dosage and approaches documented weekly. All primary and secondary efficacy outcomes rely on blinded assessments at baseline, end of treatment, and 6 mos post-treatment. Exploratory outcomes and supplemental clinical measures may provide valuable additional data about development and health in this sample of children with PAS.

Official Title
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Perinatal Arterial Stroke: A Multi-site RCT of Intensive Infant Rehabilitation (I-ACQUIRE)

Conditions
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Perinatal Stroke, Hemiparesis

Intervention / Treatment
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* Behavioral: I-ACQUIRE - High Dosage
* Behavioral: I-ACQUIRE - Moderate Dosage
* Behavioral: Usual & Customary Treatment (U&CT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: child will be 8 - 36 months old when study treatment will be delivered child has a diagnosis of Perinatal Arterial Stroke (PAS) parent permission to provide the child's clinical MRI to the study child has hemiparesis parent(s) willing to participate in the home therapy component one parent English language proficient and will take the lead in interacting with study staff and completing self-administered forms and interviews in English Exclusion Criteria: child has medical or sensory condition(s) that prevent(s) full therapy participation (e.g., frequent uncontrolled seizures, fragile health) child previously received Constraint-Induced Movement Therapy (CIMT) or modified CIMT with a dose of at least 2 hrs/day for ≥10 days child received botulinum toxin in past 3 months child is a ward of the state or other agency

Ages Eligible for Study
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Minimum Age: 8 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I-ACQUIRE High Dose<br>High Dose I-ACQUIRE (6hrs/day, 5 days/wk X 4 wks) | Behavioral: I-ACQUIRE - High Dosage<br>* Children in this group will receive 6 hours of I-ACQUIRE therapy daily, 5 days a week for 4 consecutive weeks. Treatment is delivered in the home or homelike setting by a study trained I-ACQUIRE pediatric therapist.<br>* Other names: P-CIMT;|
| Experimental: I-ACQUIRE Moderate Dose<br>Moderate Dose I-ACQUIRE (3 hrs/day, 5 day/wk X 4 wks) | Behavioral: I-ACQUIRE - Moderate Dosage<br>* Children in this group will receive 3 hours of I-ACQUIRE therapy daily, 5 days a week for 4 consecutive weeks. Treatment is delivered in the home or homelike setting by a study trained I-ACQUIRE pediatric therapist.<br>* Other names: P-CIMT;|
| Active Comparator: Usual & Customary Treatment<br>Usual & Customary Treatment | Behavioral: Usual & Customary Treatment (U&CT)<br>* Children in this group will receive the same U&CT that they had been receiving prior to the baseline assessment. The type and dosage of treatment(s) will be documented weekly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Emerging Behaviors Scale (EBS) Score | The primary efficacy is measured by the Emerging Behaviors Scale (EBS) that counts the number of upper extremity skills on the hemiparetic side that the child displays (from 0 to 30). The source for observation comes from a battery of standardized age-appropriate neuromotor assessment tools (Gross Motor Function Measure-66, The Bayley III Fine and Gross Motor scales, unilateral skills during the Mini AHA) and independent observational coding of the videotaped assessment session with supplemental parent ratings on the Infant Motor Activity Log and daily skills on the MacArthur-Bates Communicative Development Inventory. A favorable outcome is defined as a gain of ≥7 new EBS skills above the child's baseline (pre-treatment) score. The EBS requires evidence of each skill from at least two independent sources. | Both immediately after treatment (within 7 days) and 6 months (plus or minus 2 months) post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Bilateral Use of the Hemiparetic Upper Extermity based on the Mini-Assisting Hand Assessment (Mini-AHA) play assessment | The secondary efficacy outcome is measured by increases in the use of the hemiparetic upper extremity while engaged in bilateral activities during the interactive play session of the Mini-AHA. Each item is scored on a 4-pt scale where the points are behaviorally anchored and adjusted for the child's age range. Raw scores are converted into a summary Logit score (0 to 100) based on Item Response Theory analyses, indicating the relative difficulty and sequence in which certain levels of performance appear. For this metric, higher scores are considered better. | Both immediately after treatment (within 7 days) and 6 months (plus or minus 2 months) post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P-CIMT, Pediatric Constraint-Induced Movement Therapy, Hemiparesis, Perinatal Stroke, Neonatal Stroke, Pediatric rehabilitation, Infant therapy, Cerebral Palsy, ACQUIRE, I-ACQUIRE