Newborn Genomic Sequencing (BeginNGS) Prospective Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Proportion of enrolled infants who are diagnosed with a genetic disease by DWGS.
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 10 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Neonates less than or equal to 10 days old who are admitted to the RCHSD NICU.
排除标准
- •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.
- •Neonates whose mother is less than 18 years of age.
- •Neonates who are wards of the state.
- •Neonates whose parent/legal guardian is unable to provide consent.
研究组 & 干预措施
Enrollees
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).
干预措施: Whole genome sequencing (Genetic)
Enrollees
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).
干预措施: BeginNGS test (Genetic)
Enrollees
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).
干预措施: WES (Genetic)
结局指标
主要结局
Proportion of enrolled infants who are diagnosed with a genetic disease by DWGS.
时间窗: 18 months
Proportion
次要结局
- Proportion of enrolled infants who are identified with a genetic disease by BeginNGS.(18 months)
- Proportion of enrolled infants who have a positive standard NBS test.(18 months)
- Proportion of enrolled infants who are identified with a genetic disease by WES.(18 months)
- Results of confirmatory testing if BeginNGS or WES identifies a diagnostic finding not reported by DWGS.(18 months)
- Time from sample arriving in lab to return of DWGS results.(18 months)
- Proportion of parents approached who agree to participate in the study.(18 months)
- Parental reasons for refusal.(18 months)
- Time from birth to return of DWGS results.(18 months)
研究者
Stephen F. Kingsmore
President and CEO
Rady Pediatric Genomics & Systems Medicine Institute