Metabolism, Inborn ErrorsNC_NEXUSNCT02826694
North Carolina Newborn Exome Sequencing for Universal Screening
A study testing Well infant, whole exome sequencing and Diagnosed, whole exome sequencing in people with Metabolism, Inborn Errors and Hearing Loss, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 hour to 5 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolism, Inborn Errors, Hearing Loss, Hereditary Disease
- What is being tested?
- Well infant, whole exome sequencing and Diagnosed, whole exome sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 30 Jun 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 5 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Uncomplicated pregnancy and healthy newborn
Who cannot join
- Abnormalities such as major malformation or chromosomal disorder detected prenatally or significant complications during pregnancy or at the time of delivery.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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)
- Conditions
- Metabolism, Inborn Errors, Hearing Loss, Hereditary Disease
- Being tested
- Well infant, whole exome sequencing, Diagnosed, whole exome sequencing
- Medical subject headings
- Metabolism, Inborn Errors, Hearing Loss, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Well infant, whole exome sequencingGenetic
Whole exome sequencing will be performed in children with diagnosed conditions. Investigators will analyze results that are associated with their condition.
Diagnosed, whole exome sequencingGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| Well infant, whole exome sequencing | Other | 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. Receives: Genetic: Well infant, whole exome sequencing |
| Diagnosed, whole exome sequencing | Other | 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. Receives: Genetic: Diagnosed, whole exome sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: approximately 3-6 months after DNA sample obtained
Secondary outcomes (1)
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.
Measured: Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study startJun 2016
- Primary completion30 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolism, Inborn ErrorsStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI), RTI International
- Responsible party
- Sponsor
- Investigators
- Jonathan Berg, MD, PhD, Principal investigator, University of North Carolina School of Medicine Department of GeneticsCynthia M Powell, MD, Principal investigator, University of North Carolina School of Medicine Department of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02826694
- Sponsor's protocol ID
- 13-2409
- Other IDs
- 5U19HD077632
- Acronym
- NC_NEXUS
- Status last verified
- Mar 2019
- First submitted
- 21 Jun 2016
- Last updated
- 8 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Sequencing data will be shared via the Newborn Screening Translational Research Network.
Publications
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.
PubMed 29950170
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- North Carolina Newborn Exome Sequencing for Universal Screening
- ClinicalTrials.gov ID
- NCT02826694
- Acronym / sponsor ID
- NC_NEXUS / 13-2409
- Conditions
- Metabolism, Inborn Errors, Hearing Loss, Hereditary Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI), RTI International
- Study start
- Jun 2016
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 11 Jul 2016 (estimated)
- Results
- Posted 8 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Well infant, whole exome sequencing | Other | Genetic: Well infant, whole exome sequencingHealthy 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. |
| Diagnosed, whole exome sequencing | Other | Genetic: Diagnosed, whole exome sequencingInfants 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. |
Who may qualify
- Ages
- 1 hour to 5 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Uncomplicated pregnancy and healthy newborn
Key exclusion criteria (1 listed)
- Abnormalities such as major malformation or chromosomal disorder detected prenatally or significant complications during pregnancy or at the time of delivery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Well infant, whole exome sequencingWhole exome sequencing will be performed in children with diagnosed conditions. Investigators will analyze results that are associated with their condition. | Genetic | Well infant, whole exome sequencing |
| Diagnosed, whole exome sequencingIn 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. | Genetic | Diagnosed, whole exome sequencing |
Primary outcome
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.
1 secondary outcome
Parental Reaction Scores
Time frame: Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29950170Milko 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.
- Individual participant dataSharing planned: Yes. Sequencing data will be shared via the Newborn Screening Translational Research Network.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Berg, MD, PhD principal investigator
University of North Carolina School of Medicine Department of Genetics
Cynthia M Powell, MD principal investigator
University of North Carolina School of Medicine Department of Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Well infant, whole exome sequencing and Diagnosed, whole exome sequencing in people with Metabolism, Inborn Errors and Hearing Loss, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parental Choices Following Decision Aid (time frame: average of 3-6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02826694, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2020.