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
|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|
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)
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||106 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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.
- 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.
- 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.
- 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.
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
|United States, North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|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|