Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease (CHD Brain and Genes)
2 other identifiers
observational
196
1 country
8
Brief Summary
Approximately 400 Congenital heart disease patients will participate in the research study which will include one or more research visits for neurodevelopmental testing, brain MRI, and collection of medical history including previously collected genetic sequencing results. The investigators will explore the association between genetic variants, neurodevelopmental deficits, and brain MRI endophenotype. Analyses will compare groups with and without deleterious de novo mutations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Sep 2017
Typical duration for all trials
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2017
CompletedFirst Posted
Study publicly available on registry
March 3, 2017
CompletedStudy Start
First participant enrolled
September 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 29, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 29, 2020
CompletedAugust 13, 2020
January 1, 2020
2.8 years
February 28, 2017
August 12, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Neurodevelopment and behavioral health assessment
The investigators will compare groups with respect to achievement, IQ, learning disability, specific neuropsychological domains (e.g., memory, attention, executive functions, and visual-spatial/motor integration), adaptive function, behavior, social cognition and symptoms of autism spectrum disorder, and quality of life. The primary study outcome for this aim will be the WRAT4 composite score.
Day 1
Secondary Outcomes (1)
Abnormalities in brain structure and microstructure on MRI
Day 1
Study Arms (2)
Case/CHD with deleterious mutations
Participants with CHD with damaging de novo mutations or stringently defined deleterious missense mutations) on whole exome sequencing or whole genome sequencing
Control/CHD without deleterious mutations
Participants with CHD without damaging de novo mutations or stringently defined deleterious missense mutations) on whole exome sequencing or whole genome sequencing
Interventions
Brain MRI will be conducted in all participants
neurodevelopmental testing will be conducted in all participants.
Eligibility Criteria
Congenital heart disease patients aged 8 years and older with prior whole exome sequencing or whole genome sequencing results
You may qualify if:
- Subjects in whom whole exome sequencing or whole genome sequencing has already been performed, either during the CHD GENES study or, for new centers (Utah or USCF/Stanford), after trios in existing biobanks undergo analysis by whole exome sequencing or whole genome sequencing during the Pediatric Cardiac Genomic Consortium 2 grant cycle
- Presence of deleterious mutations (damaging de novo mutations or stringently defined deleterious missense mutations) identified on sequencing (Cases) OR absence of such known deleterious mutations (Controls)
- Males or females, age ≥8 years
- Diagnosis of congenital heart disease
- Informed consent obtained
You may not qualify if:
- History of cardiac transplant
- A cardiac surgical procedure within 6 months of enrollment
- Known clinical genetic syndrome, characterized as a monogenic condition with an identified gene associated with abnormalities of the brain structure or function, structural heart disease, and potentially other associated features.
- Presence of CNV known to be clinically pathogenic. Variants will be classified as pathogenic using accepted types of variant evidence (e.g., population data, computational data, functional data, segregation data) as detailed in the American College of Medical Genetics and Genomics " Standards and Guidelines for the interpretation of sequence variants" (Richards et al, GIM 2015).
- Overwhelming acquired brain injury, such as a major stroke or severe ischemic injury, that would overshadow the effect of a genetic mutation on outcome in the opinion of the center investigator
- Lack of reading fluency in English or Spanish
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
University of California, San Francisco
San Francisco, California, 94158, United States
Yale University
New Haven, Connecticut, 06520, United States
Children's Hospital Boston
Boston, Massachusetts, 02115, United States
Icahn School of Medicine at Mt. Sinai
New York, New York, 10029, United States
University of Rochester
Rochester, New York, 14642, United States
Children's Hospital Philadelphia
Philadelphia, Pennsylvania, 19104, United States
University of Utah
Salt Lake City, Utah, 84113, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jane Newburger, MD
Boston Children's Hospital
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2017
First Posted
March 3, 2017
Study Start
September 18, 2017
Primary Completion
June 29, 2020
Study Completion
June 29, 2020
Last Updated
August 13, 2020
Record last verified: 2020-01