Newborn Genomic Sequencing Pilot Study

Genetic Disease Clinical Trial

Official title:

Newborn Genomic Sequencing (BeginNGS) Prospective Pilot Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06276348
• Other study ID #: 20226892
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 13, 2023
• Est. completion date: September 2024

Study information

• Verified date: February 2024
• Source: Rady Pediatric Genomics & Systems Medicine Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: September 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 10 Days

Eligibility

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.

Related Conditions & MeSH terms

• Genetic Disease
• Genetic Diseases, Inborn

Intervention

Genetic:
• Whole genome sequencing
Standard diagnostic whole genome sequencing will be performed.
• BeginNGS test
Genomic sequencing that screens for 434 genetic diseases.
• WES
Whole exome sequencing will be performed.

Locations

Country	Name	City	State
United States	Rady Children's Hospital San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Rady Pediatric Genomics & Systems Medicine Institute

Country where clinical trial is conducted

United States, 

Outcome

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