North Carolina Newborn Exome Sequencing for Universal Screening

NCT ID: NCT02826694

Last Updated: 2020-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2019-06-30

Brief Summary

The NC NEXUS research study is exploring the utility of next generation sequencing in newborn screening and parental decision making. The National Institutes of Health (NICHD and NHGRI) are co-funding this study under a single U-19.

Detailed Description

The investigators will enroll and perform whole exome sequencing on two cohorts of patients. One cohort will consist of two hundred newborns with no known conditions whose parents will be recruited during the mother's pregnancy. The second cohort will include two hundred infants and children up to the age of five years with diagnosed conditions including conditions detected through standard newborn screening such as phenylketonuria and other inborn errors of metabolism, hearing loss and other rare conditions that may fit criteria for newborn screening in the future.

Parents will be introduced to the study by their clinician or a study recruiter. Those who agree to enroll in Phase I will review an online decision guide and be offered a study visit conducted by a genetic counselor to obtain informed consent for genomic sequencing of their child. Parents consenting to have their child's genome sequenced will be seen after the child's birth or at a convenient pre-arranged time and duplicate saliva samples will be collected from the children and one sample will be sent to the BioSpecimen Processing (BSP) Facility and to Dr. Jonathan Berg's laboratory for sequencing and the other sent to the Molecular Genetics Laboratory (MGL) for DNA extraction and storage until needed for clinical confirmation. Results will be returned for diagnostic (in the Diagnosed cohort) and medically actionable disorders of childhood (both cohorts). Two-thirds of parents who consent to sequencing will be randomly assigned to be eligible to request additional findings and use a supplement of the online decision aid. All results will be reported to parents by trained genetic professionals (genetic counselors and clinical geneticists)

Conditions

Metabolism, Inborn Errors; Hearing Loss; Hereditary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Well infant, whole exome sequencing

Healthy infants and their parents enrolled in the study prenatally will participate. After the infant is born saliva sample will be collected for DNA extraction and whole exome sequencing will be done.

Group Type: OTHER

Well infant, whole exome sequencing

Intervention Type: GENETIC

Whole exome sequencing will be performed in children with diagnosed conditions. Investigators will analyze results that are associated with their condition.

Diagnosed, whole exome sequencing

Infants and children with diagnosed conditions whose parents enroll in the study and consent to having their child sequenced will have saliva samples obtained and whole exome sequencing will be done on extracted DNA.

Group Type: OTHER

Diagnosed, whole exome sequencing

Intervention Type: GENETIC

In addition to returning results of conditions associated with a child's phenotype, investigators will also analyze genes that are associated with conditions that have childhood onset and are medically actionable.

Interventions

Well infant, whole exome sequencing

Whole exome sequencing will be performed in children with diagnosed conditions. Investigators will analyze results that are associated with their condition.

Intervention Type: GENETIC

Diagnosed, whole exome sequencing

In addition to returning results of conditions associated with a child's phenotype, investigators will also analyze genes that are associated with conditions that have childhood onset and are medically actionable.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Uncomplicated pregnancy and healthy newborn

Exclusion Criteria

• Abnormalities such as major malformation or chromosomal disorder detected prenatally or significant complications during pregnancy or at the time of delivery.

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: collaborator

RTI International

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Berg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina School of Medicine Department of Genetics

Cynthia M Powell, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina School of Medicine Department of Pediatrics

Locations

UNC Hospitals

Chapel Hill, North Carolina, United States

Countries

United States

References

Milko LV, Rini C, Lewis MA, Butterfield RM, Lin FC, Paquin RS, Powell BC, Roche MI, Souris KJ, Bailey DB Jr, Berg JS, Powell CM. Evaluating parents' decisions about next-generation sequencing for their child in the NC NEXUS (North Carolina Newborn Exome Sequencing for Universal Screening) study: a randomized controlled trial protocol. Trials. 2018 Jun 28;19(1):344. doi: 10.1186/s13063-018-2686-4.

Reference Type: DERIVED

PMID: 29950170 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

5U19HD077632

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13-2409

Identifier Type: -

Identifier Source: org_study_id