Clinical Trials Logo

Clinical Trial Summary

The goal of this clinical trial is to test a new method for newborn screening using whole genome sequencing, called BeginNGS. Parents will be approached to provide informed consent to enroll their newborns in prenatal, postnatal, and outpatient settings. The main questions this study aims to answer are: What is the utility of BeginNGS as compared to state newborn screening? What is the acceptability and feasibility of BeginNGS as compared to state newborn screening? What is the cost effectiveness of BeginNGS as compared to state newborn screening? Enrolled newborns will have a blood sample taken and will receive the BeginNGS test. Newborns will have also had the state newborn screening test.


Clinical Trial Description

Each year 98% of US newborns receive screening (NBS) of dried blood spots (DBS) for at least 35 Recommended Uniform Screening Panel (RUSP) genetic disorders for diagnosis and treatment at/before onset of symptoms. About 6,600 true positive infants are identified per year. NBS is well-accepted and has proven clinical utility. Between 2010 and 2022, however, while many new therapeutic interventions for childhood genetic diseases showed clinical utility and/or were approved by the Food and Drug Administration (FDA), only 6 disorders were added to the RUSP. As a result, ~700 childhood genetic diseases have effective treatments but are not yet screened by NBS, and affected children experience delayed diagnosis and treatment, and poor outcomes. To solve this problem the investigators are developing BeginNGS - NBS by genome sequencing (GS) of DBS for, ultimately, ~700 severe, childhood genetic diseases with effective therapeutic interventions. BeginNGS is adaptive: genetic disorders are added (or removed) as evidence emerges that early treatment improves (or does not improve) outcomes. BeginNGS version 1 (v1, 388 genetic disorders) had good sensitivity (88.8%) and false positive rate (0.27%) in a retrospective study of 458,000 subjects. An exploratory prospective clinical trial comparing BeginNGS v2 (with 409 disorders) and rapid diagnostic genome sequencing (RDGS) identified reportable findings in 24 (34%) of 71 acutely ill newborns who were not suspected of having a genetic disease. Only 2 of those disorders were detected by standard NBS. The investigators propose a single group, multicenter, adaptive clinical trial to compare utility, acceptability, feasibility, and cost effectiveness of BeginNGS (experimental intervention) with standard NBS (control) in a minimum of 10,000 neonates (aged <28 days, maximum of 100,000). The primary objective of the trial is to generate evidence to support broad implementation of BeginNGS. An adaptive design was chosen rather than a traditional, fixed design to allow accumulating results to make the trial more efficient, informative, and ethical by addition or removal of BeginNGS disorders and genetic variants, population enrichment (for minority racial, ethnic, and ancestral groups), and sample size re-estimation. Adaptive design will also facilitate meta-analysis with other clinical trials of NBS-by-GS, providing greater power to test utility in ultra-rare genetic diseases. NBS-by-GS has the potential to transform the way childhood genetic diseases are diagnosed and treatments started. Preliminary data suggest that national adoption of BeginNGS in all births has the potential to improve outcomes of >50,000 US children per year. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT06306521
Study type Interventional
Source Rady Pediatric Genomics & Systems Medicine Institute
Contact Lauren Olsen, MSN
Phone 858-576-1700
Email lolsen1@rchsd.org
Status Recruiting
Phase N/A
Start date February 29, 2024
Completion date February 2029

See also
  Status Clinical Trial Phase
Active, not recruiting NCT03548779 - North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2 N/A
Completed NCT03292302 - Phase 1 Study of ELX-02 in Healthy Adults Phase 1
Withdrawn NCT03658382 - Virtual Visits for Results Disclosure N/A
Recruiting NCT02266615 - Biobank Clinical Genetics Maastricht (KG01)
Recruiting NCT02450851 - Clinical and Genetic Evaluation of Individuals With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Recruiting NCT05472714 - Educational Video for Genetic Testing N/A
Recruiting NCT04285814 - Technology Development for Noninvasive Prenatal Genetic Diagnosis Using Whole Fetal Cells From Maternal Peripheral Blood
Completed NCT05443113 - Young Pectus Excavatum Patients and Genetic Defects
Completed NCT05655741 - Modified Delphi for Genomic Bereavement Care
Completed NCT03847909 - A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 Phase 2
Completed NCT04584528 - Implementing an Individualized Pain Plan (IPP) for ED Treatment of VOE's in Sickle Cell Disease N/A
Not yet recruiting NCT06048523 - Prospective Cohort Study of Neurogenetic Diseases N/A
Completed NCT02225522 - Genomic Sequencing in Acutely Ill Neonates N/A
Enrolling by invitation NCT06089954 - Penn Medicine Biobank Return of Results Program N/A
Completed NCT03713333 - Implementing Digital Health in a Learning Health System N/A
Completed NCT03309605 - Phase 1 Study of ELX-02 in Healthy Adult Subjects Phase 1
Recruiting NCT05499091 - Functional Study to Indentify Genetic Etiology of Rare Diseases - ORIGIN N/A
Completed NCT04556487 - Turkish Affordances in the Home Environment for Motor Development-Infant Scale (AHEMD-IS)
Completed NCT04556500 - Turkish Version of the Affordance in the Home Environment for Motor Development-Toddler (AHEMD-T)
Recruiting NCT02551081 - Genomic Sequencing and Personalized Treatment for Birth Defects in Neonatal Intensive Care Units