Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease (CHD Brain and Genes)

Heart Disease Congenital Clinical Trial

Official title:

Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03070197
• Other study ID #: 2016-6315
• Secondary ID: 5U01HL131003-02
• Status: Completed
• Start date: September 18, 2017
• Est. completion date: June 29, 2020

Study information

• Verified date: January 2020
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: June 29, 2020
• Est. primary completion date: June 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

Inclusion Criteria:

1. 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

2. 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)

3. Males or females, age =8 years

4. Diagnosis of congenital heart disease

5. Informed consent obtained

Exclusion Criteria:

1. History of cardiac transplant

2. A cardiac surgical procedure within 6 months of enrollment

3. 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.

4. 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).

5. 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

6. Lack of reading fluency in English or Spanish

Related Conditions & MeSH terms

• Heart Disease Congenital
• Heart Diseases

Intervention

Other:
• Exposure of interest: Brain MRI
Brain MRI will be conducted in all participants
• Exposure of interest: neurodevelopmental assessments
neurodevelopmental testing will be conducted in all participants.

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	Children's Hospital Philadelphia	Philadelphia	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Abnormalities in brain structure and microstructure on MRI	The investigators will compare the groups with respect to measured and derived parameters including, but not limited to, 1) regional volumetric and cortical thickness, 2) regional surface metrics, 3) voxel-based DTI eigenvectors and apparent diffusion coefficient (ADC) values, and resting state principal component analysis	Day 1

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