Clinical trial NCT06276348: Newborn Genomic Sequencing Pilot Study
Official title: Newborn Genomic Sequencing (BeginNGS) Prospective Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Genetic Disease
Lead sponsor: Rady Pediatric Genomics & Systems Medicine Institute
Sponsor class: OTHER
First posted: 2024-02-26
Enrollment: 120
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group, multiple interventions. All enrollees receive all interventions.
Primary purpose: SCREENING

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of enrolled infants who are diagnosed with a genetic disease by DWGS.
timeFrame: 18 months
Secondary outcomes:
measure: Proportion of enrolled infants who are identified with a genetic disease by BeginNGS.
timeFrame: 18 months
measure: Proportion of enrolled infants who are identified with a genetic disease by WES.
timeFrame: 18 months
measure: Proportion of enrolled infants who have a positive standard NBS test.
timeFrame: 18 months
measure: Proportion of parents approached who agree to participate in the study.
timeFrame: 18 months
measure: Parental reasons for refusal.
timeFrame: 18 months
measure: Time from sample arriving in lab to return of DWGS results.
timeFrame: 18 months
measure: Time from birth to return of DWGS results.
timeFrame: 18 months
measure: Results of confirmatory testing if BeginNGS or WES identifies a diagnostic finding not reported by DWGS.
timeFrame: 18 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
Study officials:
affiliation: Rady Children's Institute for Genomic Medicine
name: Stephen Kingsmore, MD DSc
role: PRINCIPAL_INVESTIGATOR
References: