An interventional study of Well infant, whole exome sequencing and Diagnosed, whole exome sequencing in Metabolism, Inborn Errors, Hearing Loss and Hereditary Disease, sponsored by University of North Carolina, Chapel Hill. Completed at 1 site in United States. Open to participants aged 1 Hour to 5 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-07-08.
Sponsored by University of North Carolina, Chapel Hill · Not applicable, Interventional, and Diagnostic
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.
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)
1,092 studies on the registry are indexed under Hearing Loss; 235 are open to participants now.
This study's enrollment of 106 is above the median of 40 across 764 interventional studies indexed under Hearing Loss.
Browse Hearing Loss studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.
Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.
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Exclusion Criteria:
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
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
Whole exome sequencing will be performed in children with diagnosed conditions. Investigators will analyze results that are associated with their condition.
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
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.
Time frame: average of 3-6 months
Number of Participants Identified With Genetic Conditions Through Whole Exome Sequencing
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.
Time frame: approximately 3-6 months after DNA sample obtained
Parental Reaction Scores
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.
Time frame: Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit
| Milestone | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing |
|---|---|---|
| Started | 61 | 45 |
| Decision group | 41 | 30 |
| Control group | 20 | 15 |
| Completed | 61 | 45 |
| Not completed | 0 | 0 |
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.
| Participants | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing |
|---|---|---|
| Said yes or undecided after decision aid | 120 | 57 |
| Did not want child sequenced | 25 | 2 |
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.
| Participants | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing |
|---|---|---|
| All participants — Well infant | 61 | 0 |
| All participants — Hearing Loss | 0 | 28 |
| All participants — Metabolic Disorder | 0 | 17 |
| Positive NGS/NBS result — Well infant | 1 | 0 |
| Positive NGS/NBS result — Hearing Loss | 0 | 5 |
| Positive NGS/NBS result — Metabolic Disorder | 0 | 15 |
| Negative NGS/NBS results — Well infant | 60 | 0 |
| Negative NGS/NBS results — Hearing Loss | 0 | 23 |
| Negative NGS/NBS results — Metabolic Disorder | 0 | 2 |
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.
| score on a scale | Decision Arm | Control Arm |
|---|---|---|
| T3 | 2.3 ± 2.4 | 1.7 ± 1.5 |
| T4 | 2.5 ± 2.5 | 1.5 ± 0.4 |
Collected over Adverse event data was collected beginning at Baseline and continued through Time 4 (3 months after results visit).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Well Infant, Whole Exome Sequencing | 0/61 (0%) | 0/61 (0%) | 0/61 (0%) |
| Diagnosed, Whole Exome Sequencing | 0/45 (0%) | 0/45 (0%) | 2/45 (4.4%) |
| Event | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing |
|---|---|---|
| Sample mixupCongenital, familial and genetic disorders | 0/61 | 2/45 |
Healthy newborns and children up to age 5 with a diagnosed condition
| Age, Categorical(Participants) | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing | Total |
|---|---|---|---|
| <=18 years | 61 | 45 | 106 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing | Total |
|---|---|---|---|
| Female | 29 | 28 | 57 |
| Male | 32 | 17 | 49 |
| Ethnicity (NIH/OMB)(Participants) | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing | Total |
|---|---|---|---|
| Hispanic or Latino | 8 | 2 | 10 |
| Not Hispanic or Latino | 51 | 42 | 93 |
| Unknown or Not Reported | 2 | 1 | 3 |
| Race (NIH/OMB)(Participants) | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 5 | 4 | 9 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 9 | 3 | 12 |
| White | 44 | 37 | 81 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 1 | 4 |
| Region of Enrollment(Participants) | Well Infant, Whole Exome Sequencing | Diagnosed, Whole Exome Sequencing | Total |
|---|---|---|---|
| United States | 61 | 45 | 106 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Sequencing data will be shared via the Newborn Screening Translational Research Network.
This study is completed, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.
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University of North Carolina, Chapel Hill