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North Carolina Newborn Exome Sequencing for Universal Screening (NC_NEXUS)

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ClinicalTrials.gov Identifier: NCT02826694
Recruitment Status : Active, not recruiting
First Posted : July 11, 2016
Last Update Posted : March 6, 2019
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)
Estimated Enrollment : 400 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
Estimated Primary Completion Date : June 30, 2019
Estimated 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 decision making using 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. Parent participants randomized to the decision group, after their child is sequenced, may decide what, if any, additional categories of conditions they wish to learn about. Options will be yes, no, or unsure.

  2. Sensitivity of whole exome sequencing in detecting conditions by comparing results of sequencing to the appropriate genes associated with the child's underlying condition. [ Time Frame: approximately 3-6 months after DNA sample obtained. ]
    Investigators will analyze sequencing results in the diagnosed cohort to determine the ability of whole exome sequencing to detect pathogenic variants in genes related to phenotype.


Secondary Outcome Measures :
  1. Participant characteristics and reactions to the study will be collected through surveys. [ Time Frame: Baseline and 3 months after final return of results visit. ]
    Surveys are administered at Time 1 (baseline), after parent participants decide to join phase I of the study, which involves agreeing to view the online decision aid about Next-Generation Sequencing Newborn Screening (NGS-NBS); at Time 2, after parent participants have viewed the decision aid and made a decision about accepting NGS-NBS for their child (yes/no/need more information; note that the timing is variable, depending on when participants complete this task, but may range from hours to weeks); at Time 2a (for parent participants randomly assigned to learn/make decisions about additional information), after parent participants have made the decision to accept none, some, or all categories of additional information (note that the timing is variable depending on when parent participants complete this task, but occurs after return of NGS-NBS results); Time 3, which occurs 2 weeks after return of NGS-NBS results; and Time 4, which occurs 3 months after Time 3.



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

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     History of Changes
Other Study ID Numbers: 13-2409
5U19HD077632 ( U.S. NIH Grant/Contract )
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: March 6, 2019
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
Hearing Disorders
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Metabolic Diseases