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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070197
Recruitment Status : Completed
First Posted : March 3, 2017
Last Update Posted : August 13, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

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.

Condition or disease Intervention/treatment
Heart Disease Congenital Other: Exposure of interest: Brain MRI Other: Exposure of interest: neurodevelopmental assessments

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Study Type : Observational
Actual Enrollment : 196 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease
Actual Study Start Date : September 18, 2017
Actual Primary Completion Date : June 29, 2020
Actual Study Completion Date : June 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases

Group/Cohort Intervention/treatment
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
Other: Exposure of interest: Brain MRI
Brain MRI will be conducted in all participants

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

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
Other: Exposure of interest: Brain MRI
Brain MRI will be conducted in all participants

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




Primary Outcome Measures :
  1. Neurodevelopment and behavioral health assessment [ Time Frame: Day 1 ]
    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.


Secondary Outcome Measures :
  1. Abnormalities in brain structure and microstructure on MRI [ Time Frame: Day 1 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Congenital heart disease patients aged 8 years and older with prior whole exome sequencing or whole genome sequencing results
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070197


Locations
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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
University of California, San Francisco
San Francisco, California, United States, 94158
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New York
Icahn School of Medicine at Mt. Sinai
New York, New York, United States, 10029
University of Rochester
Rochester, New York, United States, 14642
United States, Pennsylvania
Children's Hospital Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84113
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Jane Newburger, MD Boston Children's Hospital
Additional Information:
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03070197    
Other Study ID Numbers: 2016-6315
5U01HL131003-02 ( U.S. NIH Grant/Contract )
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: August 13, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases