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North Carolina Newborn Exome Sequencing for Universal Screening (NC_NEXUS)

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: NCT02826694
Recruitment Status : Completed
First Posted : July 11, 2016
Results First Posted : July 8, 2020
Last Update Posted : July 8, 2020
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Human Genome Research Institute (NHGRI)
RTI International
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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.

Condition or disease Intervention/treatment Phase
Metabolism, Inborn Errors Hearing Loss Hereditary Disease Genetic: Well infant, whole exome sequencing Genetic: Diagnosed, whole exome sequencing Not Applicable

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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: North Carolina Newborn Exome Sequencing for Universal Screening
Study Start Date : June 2016
Actual Primary Completion Date : June 30, 2019
Actual Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Genetic: 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.

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.
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.




Primary Outcome Measures :
  1. Parental Choices Following Decision Aid [ Time Frame: average of 3-6 months ]
    Analysis of parents' decisions after they complete an on-line decision aid to see if they wish to participate in the study. Options will be yes, no, or undecided.

  2. Number of Participants Identified With Genetic Conditions Through Whole Exome Sequencing [ Time Frame: approximately 3-6 months after DNA sample obtained ]
    Investigators analyzed next generation sequencing (NGS) results in the diagnosed cohort to determine the ability of whole exome sequencing to detect pathogenic variants in genes related to phenotype determined by standard newborn screening (NBS). The category of genes analyzed is termed the Next Generation Sequencing/Newborn Screening (NGS/NBS) category. Healthy newborns with no known genetic conditions also had the NGS/NBS category of genes analyzed.


Secondary Outcome Measures :
  1. Parental Reaction Scores [ Time Frame: Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit ]
    Test-related distress is assessed with an adapted version of the Multidimensional Impact of Cancer Risk Assessment (MICRA). It asks participants to report how often in the past week they have experienced worries and distress related to their child's genomic sequencing procedure and test results, and the social and familial consequences of sequencing and the test results. Possible responses are provided on the following scale: 0=Never, 1=Rarely, 3=Sometimes, and 5=Often. Because it refers to respondents' experience of their child's sequencing and the test results they received, it is administered only in assessments that occurred after sequencing at Time 3 (2 weeks after results visit and Time 4 (3 months after results visit). Comparisons are made between couples who could chose to receive additional information about their child's genome and a control group who were not eligible to receive additional information.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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): NCT02826694


Locations
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United States, North Carolina
UNC Hospitals
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Human Genome Research Institute (NHGRI)
RTI International
Investigators
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Principal Investigator: Jonathan Berg, MD, PhD University of North Carolina School of Medicine Department of Genetics
Principal Investigator: Cynthia M Powell, MD University of North Carolina School of Medicine Department of Pediatrics
  Study Documents (Full-Text)

Documents provided by University of North Carolina, Chapel Hill:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02826694    
Other Study ID Numbers: 13-2409
5U19HD077632 ( U.S. NIH Grant/Contract )
First Posted: July 11, 2016    Key Record Dates
Results First Posted: July 8, 2020
Last Update Posted: July 8, 2020
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Sequencing data will be shared via the Newborn Screening Translational Research Network.
Additional relevant MeSH terms:
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Hearing Loss
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Metabolic Diseases