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

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).

Study Overview

• Status: Completed
• Conditions: Hemiparesis; Perinatal Stroke
• Intervention / Treatment: Behavioral: I-ACQUIRE - High Dosage; Behavioral: I-ACQUIRE - Moderate Dosage; Behavioral: Usual & Customary Treatment (U&CT)

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 216 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 Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • USCD Health La Jolla
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale New Haven Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Kennedy Krieger Institute - Fairmount Rehabilitation
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C.S. Mott Children's Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine, St. Louis Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43210
      • Martha Morehouse Medical Plaza
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • The Medical University of South Carolina (MUSC)
  • Texas
    • Dallas, Texas, United States, 75219
      • Scottish Rite for Children - Dallas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Texas Medical Center
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Fralin Biomedical Research Institute at Virginia Tech
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 3 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / 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	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Virginia Polytechnic Institute and State University
• Collaborators: Medical University of South Carolina; Stanford University; Ohio State University; Nationwide Children's Hospital; University of Cincinnati
• 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

Publications and helpful links

General Publications

• Ramey SL, Lo WD, DeLuca SC, Heathcock JC, Darragh AR, Ramey CT, Wintermark M, Martin RH, Conaway MR, Wolf SL, Janis LS, Broderick JP. Perinatal Arterial Ischemic Stroke Phase 3 Trial Protocol for Intensive Infant-Toddler Rehabilitation (I-ACQUIRE). Stroke. 2026 Mar;57(3):614-621. doi: 10.1161/STROKEAHA.125.053375. Epub 2026 Feb 6.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2019
• Primary Completion (Actual): July 16, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cerebral Palsy; Hemiparesis; Pediatric rehabilitation; Perinatal Stroke; P-CIMT; Neonatal Stroke; Pediatric Constraint-Induced Movement Therapy; Infant therapy; ACQUIRE; I-ACQUIRE
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Damage, Chronic; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cerebral Palsy; Paresis
• Other Study ID Numbers: 1U01NS106655-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Public use dataset from the study data will be made available.
• IPD Sharing Time Frame: Approximately 1 year after primary data analysis publications
• IPD Sharing Access Criteria: standard NIH criteria
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Study Data/Documents

1. Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No