Newborn Genomic Sequencing Pilot Study

Not Applicable

Completed

• Conditions: Genetic Disease
• Interventions: Genetic: Whole genome sequencing; Genetic: BeginNGS test; Genetic: WES

• Registration Number: NCT06276348
• Lead Sponsor: Rady Pediatric Genomics & Systems Medicine Institute

Brief Summary

The goal of this clinical trial is to test a new method for newborn screening using whole genome sequencing, called BeginNGS. Newborns who are not suspected of having genetic diseases and who are admitted to the NICU at Rady Children's Hospital, San Diego, will be enrolled. The main questions this study aims to answer are:

* What is the diagnostic yield of diagnostic whole genome sequencing (DWGS) in this population?

* What is the diagnostic sensitivity and specificity of BeginNGS and whole exome sequencing (WES) as compared to DWGS?

* What are the potential issues related to implementing DWGS in this population?

Enrolled newborns will have a blood sample taken and will receive three tests:

* DWGS

* BeginNGS

* WES

Detailed Description

Newborn screening (NBS) by testing dried blood spots (DBS) identifies newborns with a few diseases for which effective treatments are available to enable treatment at or before symptom onset. Because NBS improves outcomes in these diseases, it is performed on almost all US babies. The current Federal recommended NBS list is limited to 35 conditions and identifies \~6,600 affected children per year. In genetic diseases not screened by NBS, however, outcomes remain poor because of delays in diagnosis and treatment. The investigators recently developed a system for NBS for 434 severe, childhood genetic diseases for which effective treatments are available using whole genome sequencing (WGS), called BeginNGS. Retrospective studies showed BeginNGS to have a true negative rate (specificity) of 99.7% and true positive rate (sensitivity) of 88.8%. The investigators now propose to undertake a first prospective study in newborns admitted to the Neonatal Intensive Care Unit (NICU) at Rady Children's Hospital, San Diego (RCHSD) to compare the sensitivity and specificity of BeginNGS with that of standard, diagnostic rapid whole genome sequencing (DWGS) and whole exome sequencing (WES). This study is in preparation for larger, future clinical trials.

Study Timeline

• Study Start: 2023-03-13
• Study First Submitted: 2024-02-16
• Study First Submitted QC: 2024-02-16
• Study First Posted: 2024-02-26
• Primary Completion: 2024-02-28
• Status Verified: 2024-11
• Study Completion: 2024-11-12
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Neonates less than or equal to 10 days old who are admitted to the RCHSD NICU.

Exclusion Criteria

1. Neonates who have enrolled in another clinical study at Rady Children's Institute for Genomic Medicine or in whom DWGS has been ordered or is being considered.
2. Neonates whose mother is less than 18 years of age.
3. Neonates who are wards of the state.
4. Neonates whose parent/legal guardian is unable to provide consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Enrollees	Whole genome sequencing	Enrolled infants will receive 3 tests (DWGS, BeginNGS, and WES). DWGS will be performed in a standard manner. BeginNGS and WES will be performed in a batch after completion of enrollment. The diagnostic sensitivity and specificity of BeginNGS and WES will be compared to DWGS (a standard clinical test compliant with the Clinical Laboratory Improvement Amendments Act).
Enrollees	WES	Enrolled infants will receive 3 tests (DWGS, BeginNGS, and WES). DWGS will be performed in a standard manner. BeginNGS and WES will be performed in a batch after completion of enrollment. The diagnostic sensitivity and specificity of BeginNGS and WES will be compared to DWGS (a standard clinical test compliant with the Clinical Laboratory Improvement Amendments Act).
Enrollees	BeginNGS test	Enrolled infants will receive 3 tests (DWGS, BeginNGS, and WES). DWGS will be performed in a standard manner. BeginNGS and WES will be performed in a batch after completion of enrollment. The diagnostic sensitivity and specificity of BeginNGS and WES will be compared to DWGS (a standard clinical test compliant with the Clinical Laboratory Improvement Amendments Act).

Primary Outcome Measures

Name	Time	Method
Proportion of enrolled infants who are diagnosed with a genetic disease by DWGS.	18 months	Proportion

Secondary Outcome Measures

Name	Time	Method
Proportion of enrolled infants who are identified with a genetic disease by BeginNGS.	18 months	Proportion
Proportion of enrolled infants who have a positive standard NBS test.	18 months	Proportion
Proportion of enrolled infants who are identified with a genetic disease by WES.	18 months	Proportion
Results of confirmatory testing if BeginNGS or WES identifies a diagnostic finding not reported by DWGS.	18 months	Proportion of findings confirmed
Time from sample arriving in lab to return of DWGS results.	18 months	Time (days)
Proportion of parents approached who agree to participate in the study.	18 months	Proportion
Parental reasons for refusal.	18 months	Questionnaire
Time from birth to return of DWGS results.	18 months	Time (days)

Trial Locations

Locations (1)

Rady Children's Hospital San Diego; 🇺🇸 San Diego, California, United States