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

Sponsor

Virginia Polytechnic Institute and State University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03910075

Collaborator

Ohio State University (Other), Nationwide Children's Hospital (Other), Stanford University (Other), University of Cincinnati (Other), Medical University of South Carolina (Other)

240

Enrollment

Locations

Arms

55.2

Anticipated Duration (Months)

18.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Perinatal Stroke Hemiparesis	Behavioral: I-ACQUIRE - High Dosage Behavioral: I-ACQUIRE - Moderate Dosage Behavioral: Usual & Customary Treatment (U&CT)	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 10, 2019

Anticipated Primary Completion Date :

Feb 15, 2024

Anticipated Study Completion Date :

May 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I-ACQUIRE High Dose High Dose I-ACQUIRE (6hrs/day, 5 days/wk X 4 wks)	Behavioral: I-ACQUIRE - High Dosage 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. Other Names: ACQUIRE Pediatric Constraint-Induced Movement Therapy P-CIMT
Experimental: I-ACQUIRE Moderate Dose Moderate Dose I-ACQUIRE (3 hrs/day, 5 day/wk X 4 wks)	Behavioral: I-ACQUIRE - Moderate Dosage 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. Other Names: ACQUIRE Pediatric Constraint-Induced Movement Therapy P-CIMT
Active Comparator: Usual & Customary Treatment Usual & Customary Treatment	Behavioral: Usual & Customary Treatment (U&CT) 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.

Arm

Intervention/Treatment

Experimental: I-ACQUIRE High Dose

High Dose I-ACQUIRE (6hrs/day, 5 days/wk X 4 wks)

Behavioral: I-ACQUIRE - High Dosage

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.

Other Names:

ACQUIRE

Pediatric Constraint-Induced Movement Therapy

P-CIMT

Experimental: I-ACQUIRE Moderate Dose

Moderate Dose I-ACQUIRE (3 hrs/day, 5 day/wk X 4 wks)

Behavioral: I-ACQUIRE - Moderate Dosage

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.

Other Names:

ACQUIRE

Pediatric Constraint-Induced Movement Therapy

P-CIMT

Active Comparator: Usual & Customary Treatment

Usual & Customary Treatment

Behavioral: Usual & Customary Treatment (U&CT)

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.

Outcome Measures

Primary Outcome Measures

Changes in Emerging Behaviors Scale (EBS) Score [Both immediately after treatment (within 7 days) and 6 months (plus or minus 2 months) post-treatment]
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.

Secondary Outcome Measures

Changes in Bilateral Use of the Hemiparetic Upper Extermity based on the Mini-Assisting Hand Assessment (Mini-AHA) play assessment [Both immediately after treatment (within 7 days) and 6 months (plus or minus 2 months) post-treatment]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Months to 36 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USCD Health La Jolla	La Jolla	California	United States	92037
2	Yale New Haven Children's Hospital	New Haven	Connecticut	United States	06511
3	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	Kennedy Krieger Institute - Fairmount Rehabilitation	Baltimore	Maryland	United States	21231
5	Boston Children's Hospital	Boston	Massachusetts	United States	02115
6	C.S. Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
7	Washington University School of Medicine, St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
8	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
9	Martha Morehouse Medical Plaza	Columbus	Ohio	United States	43210
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	The Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
12	Memorial Hermann Texas Medical Center	Houston	Texas	United States	77030
13	Fralin Biomedical Research Institute at Virginia Tech	Roanoke	Virginia	United States	24016

Sponsors and Collaborators

Virginia Polytechnic Institute and State University
Ohio State University
Nationwide Children's Hospital
Stanford University
University of Cincinnati
Medical University of South Carolina

Investigators

Principal Investigator: Sharon L Ramey, Ph.D., Virginia Polytechnic Institute and State University
Principal Investigator: Warren Lo, M.D., Children's National Research Institute