Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 5U19HD077632 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| National Human Genome Research Institute (NHGRI) | NIH |
| RTI International | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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)
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Well infant, whole exome sequencing | Genetic | Whole exome sequencing will be performed in children with diagnosed conditions. Investigators will analyze results that are associated with their condition. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | approximately 3-6 months after DNA sample obtained |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UNC Hospitals | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29950170 | Derived | 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. |
Not provided
Not provided
Sequencing data will be shared via the Newborn Screening Translational Research Network.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. Investigators will analyze results associated with childhood onset, medically actionable conditions. |
| FG001 | 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. In addition to returning results of conditions associated with the child's phenotype, investigators will also analyze genes that are associated with conditions that have childhood onset and are medically actionable. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Healthy newborns and children up to age 5 with a diagnosed condition
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. Investigators will analyze genes that are associated with conditions that have childhood onset and are medically actionable. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Those parents initially approached received an email link to the 1st Decision Aid. However, they were not considered enrolled unless they came for an in-person consent visit and elected to have their child's genome sequenced. | Posted | Count of Participants | Participants | average of 3-6 months |
|
Adverse event data was collected beginning at Baseline and continued through Time 4 (3 months after results visit).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sample mixup | Congenital, familial and genetic disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Cynthia M. Powell | The University of North Carolina at Chapel Hill | 9199667646 | powellcm@med.unc.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 18, 2013 | May 29, 2020 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D008661 | Metabolism, Inborn Errors |
| D034381 | Hearing Loss |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006311 | Hearing Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000073359 | Exome Sequencing |
| ID | Term |
|---|---|
| D000073336 | Whole Genome Sequencing |
| D017422 | Sequence Analysis, DNA |
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Diagnosed, whole exome sequencing | Genetic | 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. |
|
| Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit |
| BG001 |
| 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. In addition to returning results of conditions associated with the child's phenotype, investigators will also analyze genes that are associated with conditions that have childhood onset and are medically actionable. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| 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. 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 | 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. | By definition, there were no well infants in the "Diagnosed, whole exome sequencing" Arm category. | Posted | Count of Participants | Participants | approximately 3-6 months after DNA sample obtained |
|
|
|
| Secondary | 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. | Total number completing T3 and T4 MICRA scales | Posted | Mean | Standard Deviation | score on a scale | Time 3 - 2 weeks after results visit and Time 4 - 3 months after results visit |
|
|
|
|
| 0 |
| 61 |
| 0 |
| 61 |
| 0 |
| 61 |
| EG001 | 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. 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. | 0 | 45 | 0 | 45 | 2 | 45 |
Not provided
Not provided
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008919 |
| Investigative Techniques |
| Hearing Loss |
|
| Metabolic Disorder |
|
| Positive NGS/NBS result |
|
|
| Negative NGS/NBS results |
|
|
| 0.026 |
| Other |