Congenital Heart Disease: Impact on Learning and Development in Down Syndrome (CHILD-DS) (CHILD-DS)

• ClinicalTrials.gov Identifier: NCT05312177
• Recruitment Status: Recruiting
• First Posted: April 5, 2022
• Last Update Posted: August 5, 2022
• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Information provided by (Responsible Party): HealthCore-NERI

Tracking Information

• First Submitted Date: February 24, 2020
• First Posted Date: April 5, 2022
• Last Update Posted Date: August 5, 2022
• Actual Study Start Date: May 30, 2022
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 12, 2022)

• Neurodevelopmental outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without major CHD. [ Time Frame: 1 day ]
  Verbal and non-verbal ratio intelligent quotients (IQs) derived from the Stanford Binet Intelligence Scales will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Behavioral outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without major CHD. [ Time Frame: 1 day ]
  Adaptive composite scores from the Vineland Adaptive Behavior Scales will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Language abilities compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Peabody Picture Vocabulary Test, Expressive Vocabulary Test, and Leiter International Performance Scale total language, auditory comprehension, and expressive communication will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Emotional outcomes compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Repetitive Behavior Scale and Aberrant Behavior Checklist , behavioral and emotional problems will be compared will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Social Communication compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Social Communication Questionnaire, social communication, social interactions, play and behavior will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.

Original Primary Outcome Measures (submitted: March 31, 2022)

• Neurodevelopmental outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without major CHD. [ Time Frame: 1 day ]
  Verbal and non-verbal ratio intelligent quotients (IQs) derived from the Mullen Scales of Early Learning will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Behavioral outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without major CHD. [ Time Frame: 1 day ]
  Adaptive composite scores from the Vineland Adaptive Behavior Scales will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Language abilities compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Preschool Language Scales, total language, auditory comprehension, and expressive communication will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Emotional outcomes compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Child Behavior Checklist, behavioral and emotional problems will be compared will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Executive functioning compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Behavior Rating of Executive Functioning, Preschool Version, the five primary scales of Inhibit, Shift, Emotional Control, Working Memory, and Planning/Organization will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Social Communication compared between the children with DS and CAVSD repair and the children with DS without major CHD. [ Time Frame: 1 day ]
  Using the Social Communication Questionnaire, social communication, social interactions, play and behavior will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.

Current Secondary Outcome Measures (submitted: May 12, 2022)

• Comorbidities as predictors of neurodevelopment and behavior [ Time Frame: 1 day ]
  Comorbidities will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Sociodemographic factors as predictors of neurodevelopment and behavior [ Time Frame: 1 day ]
  Sociodemographic factors, such as will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.

Original Secondary Outcome Measures (submitted: March 31, 2022)

• Comorbidities as predictors of neurodevelopment and behavior [ Time Frame: 1 day ]
  Comorbidities will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.
• Sociodemographic factors as predictiors of neurodevelopment and behavior [ Time Frame: 1 day ]
  Sociodemographic factors, such as will be compared between the children with DS and CAVSD repair and the children with DS without major CHD.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Congenital Heart Disease: Impact on Learning and Development in Down Syndrome (CHILD-DS)
• Official Title: Congenital Heart Disease: Impact on Learning and Development in Down Syndrome (CHILD-DS)
• Brief Summary: The study objective is to compare neurodevelopmental (ND) and behavioral outcomes between children with Down syndrome (DS) who had complete atrioventricular septal defect (CAVSD) repair and children from the same clinical sites with DS without major congenital heart disease (CHD) requiring previous or planned CHD surgery.
• Detailed Description: We will conduct a multicenter cohort study, ancillary to the Pediatric Heart Network (PHN) Residual Lesion Score (RLS) study, to investigate determinants of ND and behavioral outcomes in children with DS, focusing on the role of CHD surgery. We will only include RLS Study children with DS who had CAVSD repair, as this group comprises 91% of all children with DS in the RLS Study, with similar underlying congenital cardiac defect and surgical repair complexity, allowing our children with DS and CHD to be a homogeneous group. Moreover, one in five individuals with DS is born with an AVSD, a 2000 times higher incidence than in those with normal chromosomes. In addition to recruiting RLS Study children with DS who had CAVSD repair, we will recruit similarly-aged children with DS who do not have documented major CHD (i.e., CHD requiring previous or planned CHD surgery) to come into the same PHN site for a single study visit consisting of detailed phenotyping by completion of a Health & Developmental History Intake form, ND and behavioral assessments, and optional collection and storage of saliva specimens in the PHN Biorepository. By building our sample from RLS Study participants and recruiting a comparison group from the same PHN sites, we will leverage rich prospective data in a group of DS children with CAVSD repair from a nationally representative sample, and the expertise of the PHN and Boston Children's Hospital (BCH).
• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

We aim to collect saliva samples from study participants during the single study visit at the PHN site, which will be preserved and processed by the PHN Biorepository for DNA storage for future targeted research studies.

• Sampling Method: Non-Probability Sample
• Study Population: PHN RLS Study participants with DS and CAVSD repair from the 13 PHN sites are eligible to participate in this study. Children with a diagnosis of mosaic DS will be excluded, as these forms of DS show different ND trajectories and are usually excluded. While data on mosaic DS were not collected in the RLS Study, we anticipate few if any to have this diagnosis. The DS comparison group will be required to have no major CHD, defined as CHD that requires CHD surgery (a) in the period between birth and recruitment into the CHILD-DS Study or (b) planned for a future date.

Condition

• Down Syndrome
• Congenital Heart Disease

Intervention

• Other: Stanford Binet Intelligence Scales, Fifth Edition
  The SB-5 is a comprehensive measure of cognitive and intellectual functioning for individuals from age two through 85 years of age. The SB-5 individually assess a child's functioning in five areas of cognitive functioning: Fluid Reasoning, Knowledge, Quantitative Reasoning, Visual Spatial, and Working Memory. The SB-5 is well established in the existing research literature as an assessment tool to evaluate developmental and intellectual abilities in children with ND disorders.
  Other Name: SB-5
• Other: Vineland Adaptive Behavior Scales Third Edition
  The VABS-3 are a parent report, interview style measure of adaptive behavior for individuals ages birth through 90 months. The VABS-3 assesses adaptive behavior in four broad domains of Communication, Daily Living Skills, Socialization, and Motor Skills, and includes a Maladaptive Behavior Domain that assesses problem behaviors.
  Other Name: VABS-3
• Other: Peabody Picture Vocabulary Test, Fifth Edition
  The PPVT-5 is a norm-referenced language measure that evaluates single-word receptive vocabulary. The PPVT-5 provides standard scores for individuals ages 2.6 through 90 years.
  Other Name: PPVT-5
• Other: Expressive Vocabulary Test, Third Edition
  The EVT-3 is a norm-referenced language measure that evaluates single-word expressive vocabulary. The EVT-3 provides standard scores for individuals ages 2.6 through 90 years.
  Other Name: EVT-3
• Other: Leiter International Performance Scale, Third Edition
  The Leiter-3 is a nonverbal measure of cognitive functioning and fluid reasoning skills in individuals ages 3 through 75 years. The Leiter-3 measures nonverbal IQ across four subscales, including Sequential Order (SO), Form Completion (FC), Classification and Analogies (CA), and Figure Ground (FG).
  Other Name: Leiter-3
• Other: Social Communication Questionnaire, Current Form
  The SCQ is a parent-report measure of social communication, social interactions, play, and behavior.
  Other Name: SCQ
• Other: Aberrant Behavior Checklist
  The ABC-2 is a parent report measure of problematic behavior at home and in the community. It measures behavior on five subscales (1) Irritability, (2) Social Withdrawal, (3) Stereotypic Behavior, (4) Hyperactivity/Noncompliance, and (5) Inappropriate Speech.
  Other Name: ABC-2
• Other: Repetitive Behavior Scale, Revised
  The RBS-R is a parent report measure that comprehensively surveys for the presence of repetitive behaviors.
  Other Name: RBS-R

Study Groups/Cohorts

• DS with CAVSD Repair
  Children between the ages of 5 and 8 years with Down syndrome who had Complete atrioventricular septal defect (CAVSD) repair in the first year of life and their parent(s) will be administered the Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5), Expressive Vocabulary Test, Third Edition (EVT-3), Leiter International Performance Scale, Third Edition (Leiter-3), Vineland-3 Q-global Comprehensive Report (Vineland-3) ,Social Communication Questionnaire, Current version (SCQ), Aberrant Behavior Checklist, Second Edition, (ABC-2) and Repetitive Behavior Scale, Revised (RBS-R)
  Interventions:

  • Other: Stanford Binet Intelligence Scales, Fifth Edition
  • Other: Vineland Adaptive Behavior Scales Third Edition
  • Other: Peabody Picture Vocabulary Test, Fifth Edition
  • Other: Expressive Vocabulary Test, Third Edition
  • Other: Leiter International Performance Scale, Third Edition
  • Other: Social Communication Questionnaire, Current Form
  • Other: Aberrant Behavior Checklist
  • Other: Repetitive Behavior Scale, Revised
• DS without major CHD
  Children between the ages of 5 and 8 years with Down syndrome without major Congenital Heart Disease(CHD) and their parent(s) will be administered the Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5), Expressive Vocabulary Test, Third Edition (EVT-3), Leiter International Performance Scale, Third Edition (Leiter-3), Vineland-3 Q-global Comprehensive Report (Vineland-3) ,Social Communication Questionnaire, Current version (SCQ), Aberrant Behavior Checklist, Second Edition, (ABC-2) and Repetitive Behavior Scale, Revised (RBS-R)
  Interventions:

  • Other: Stanford Binet Intelligence Scales, Fifth Edition
  • Other: Vineland Adaptive Behavior Scales Third Edition
  • Other: Peabody Picture Vocabulary Test, Fifth Edition
  • Other: Expressive Vocabulary Test, Third Edition
  • Other: Leiter International Performance Scale, Third Edition
  • Other: Social Communication Questionnaire, Current Form
  • Other: Aberrant Behavior Checklist
  • Other: Repetitive Behavior Scale, Revised

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 12, 2022): 320
• Original Estimated Enrollment (submitted: March 31, 2022): 321
• Estimated Study Completion Date: June 30, 2023
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Down Syndrome CAVSD Repair Group:

• Trisomy 21
• Male or Female, age 5 years through 8 years
• Pediatric Heart Network (PHN) Residual Lesion Score (RLS) study participant having CAVSD repair within the first year of life at a subset of recruitment sites
• Parent or guardian and patient willing to comply with protocol, complete all study assessments, and provide written informed consent using the English language
• Child and parent able to speak and understand English

Down Syndrome Comparison Group

• Trisomy 21
• Male or Female, age 5 years through 8 years
• No major CHD, defined as CHD requiring previous or planned CHD surgery
• Parent or guardian and patient willing to comply with protocol, complete all study assessments, and provide written informed consent using the English language
• Child and parent able to speak and understand English

Exclusion Criteria:

Both Groups

- Mosaic DS

Down Syndrome CAVSD Repair Group only - Not a participant in the PHN RLS Study

Down Syndrome Comparison Group only

- Major CHD requiring previous or planned CHD surgery - i.e., CHD surgery occurring (a) in the period between birth and time of recruitment into the CHILD-DS Study, or (b) planned for a future date.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Months to 108 Months (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Maria VanRompay, PhD; 617-584-7142; MVanRompay@HealthCore.com

Contact: Melissa Lamberti, MSW; 339-222-2804; mlamberti@healthcore.com

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT05312177
• Other Study ID Numbers: CHILD-DS; 3U24HL135691-03S1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Public Use Datasets are created after study closeout and are made available on the PHN public website. Annotated study data collection forms, Statistical Analysis Program (SAS) datasets, and excel datasets are made available, as well as de-identified study cohort characteristics.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data is available one year after study closeout and is available indefinitely.
• Access Criteria: log-in and password
• URL: https://www.pediatricheartnetwork.org/login/

• Current Responsible Party: HealthCore-NERI
• Original Responsible Party: Same as current
• Current Study Sponsor: HealthCore-NERI
• Original Study Sponsor: Same as current

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Maria VanRompay, PhD; HealthCore-NERI

• PRS Account: HealthCore-NERI
• Verification Date: March 2022