Heart Disease CongenitalNCT03070197
Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease (CHD Brain and Genes)
An observational study of Heart Disease Congenital, run by Children's Hospital Medical Center, Cincinnati at 8 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- Heart Disease Congenital
- What is being tested?
- Exposure of interest: Brain MRI and Exposure of interest: neurodevelopmental assessments
- How many people
- 196 participants
- Where
- 8 sitesUnited States
- Study dates
- 18 Sep 2017to 29 Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Congenital heart disease patients aged 8 years and older with prior whole exome sequencing or whole genome sequencing results
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Children's Hospital Boston
Boston, Massachusetts, 02115
Children's Hospital Los Angeles
Los Angeles, California, 90027
Yale University
New Haven, Connecticut, 06520
Icahn School of Medicine at Mt. Sinai
New York, New York, 10029
Children's Hospital Philadelphia
Philadelphia, Pennsylvania, 19104
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84113
University of California, San Francisco
San Francisco, California, 94158
About this study
Official title: Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease
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.
- Conditions
- Heart Disease Congenital
- Being tested
- Exposure of interest: Brain MRI, Exposure of interest: neurodevelopmental assessments
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exposure of interest: Brain MRIOther
Brain MRI will be conducted in all participants
Exposure of interest: neurodevelopmental assessmentsOther
neurodevelopmental testing will be conducted in all participants.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: Exposure of interest: Brain MRI; Other: Exposure of interest: neurodevelopmental assessments | |
| 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 Receives: Other: Exposure of interest: Brain MRI; Other: Exposure of interest: neurodevelopmental assessments |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1
Secondary outcomes (1)
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
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start18 Sep 2017
- Primary completion29 Jun 2020
- Study completion29 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Disease CongenitalStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 196 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Jane Newburger, MD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070197
- Sponsor's protocol ID
- 2016-6315
- Other IDs
- 5U01HL131003-02
- Status last verified
- Jan 2020
- First submitted
- 28 Feb 2017
- Last updated
- 13 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease
- ClinicalTrials.gov ID
- NCT03070197
- Acronym / sponsor ID
- 2016-6315
- Conditions
- Heart Disease Congenital
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 196 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 18 Sep 2017 (actual)
- Primary completion
- 29 Jun 2020 (actual)
- Study completion
- 29 Jun 2020 (actual)
- First posted
- 3 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case/CHD with deleterious mutations | – | Other: Exposure of interest: Brain MRI, Other: Exposure of interest: neurodevelopmental assessmentsParticipants 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 | – | Other: Exposure of interest: Brain MRI, Other: Exposure of interest: neurodevelopmental assessmentsParticipants with CHD without damaging de novo mutations or stringently defined deleterious missense mutations) on whole exome sequencing or whole genome sequencing |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Congenital heart disease patients aged 8 years and older with prior whole exome sequencing or whole genome sequencing results
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exposure of interest: Brain MRIBrain MRI will be conducted in all participants | Other | Case/CHD with deleterious mutations, Control/CHD without deleterious mutations |
| Exposure of interest: neurodevelopmental assessmentsneurodevelopmental testing will be conducted in all participants. | Other | Case/CHD with deleterious mutations, Control/CHD without deleterious mutations |
Primary outcome
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.
1 secondary outcome
Abnormalities in brain structure and microstructure on MRI
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2020.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane Newburger, MD principal investigator
Boston Children's Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Disease Congenital, run by Children's Hospital Medical Center, Cincinnati at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurodevelopment and behavioral health assessment (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2020.