Clinical trial NCT02826694: North Carolina Newborn Exome Sequencing for Universal Screening
Official title: North Carolina Newborn Exome Sequencing for Universal Screening
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolism, Inborn Errors
Hearing Loss
Hereditary Disease
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Human Genome Research Institute (NHGRI)
name: RTI International
First posted: 2016-07-11
Enrollment: 106
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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)

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.

Primary outcomes:
measure: Parental Choices Following Decision Aid
timeFrame: average of 3-6 months
measure: Number of Participants Identified With Genetic Conditions Through Whole Exome Sequencing
timeFrame: approximately 3-6 months after DNA sample obtained
Secondary outcomes:
measure: Parental Reaction Scores
timeFrame: Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Hospitals
state: North Carolina
Study officials:
affiliation: University of North Carolina School of Medicine Department of Genetics
name: Jonathan Berg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina School of Medicine Department of Pediatrics
name: Cynthia M Powell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.