Genomic Sequencing for Genetic Disorders

(rWGS Trial)

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Rady Pediatric Genomics & Systems Medicine Institute

Disqualifiers: Prior diagnosis, Insufficient presentation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to use Rapid Whole Genome Sequencing (rWGS) to quickly diagnose genetic disorders in sick children. The researchers seek to determine if rWGS aids doctors in making better treatment decisions and if it reduces costs compared to traditional methods. Children under four months old, who are very sick and suspected of having a genetic condition, might be suitable candidates. The study will also store genetic samples for future research. As an unphased trial, participants can contribute to groundbreaking research that could enhance diagnostic methods for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that rapid whole genome sequencing is safe for pediatric patients?

Research has shown that rapid Whole Genome Sequencing (rWGS) is generally safe. In studies with hospitalized infants who might have genetic disorders, rWGS was well-tolerated, with no major reports of problems directly caused by the sequencing process. This suggests that rWGS does not pose any immediate safety risks.

rWGS quickly reads all of a person's DNA to identify genetic issues. Hospitals have used it to rapidly diagnose genetic disorders in very sick infants. The goal is to obtain results quickly without harming the patient. While the process involves taking a blood sample, which is common in medical tests, the sequencing itself is non-invasive.

Overall, research supports the safety of rWGS in medical practice, particularly for diagnosing genetic conditions in children. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about rapid whole genome sequencing for genetic disorders because it offers a groundbreaking approach to diagnosing these conditions. Unlike traditional methods, which often involve a lengthy process of testing individual genes, this technique can quickly analyze a person's entire genome in one go. This can lead to faster and more accurate diagnoses, especially in complex cases where multiple genes might be involved. By enabling quicker identification of genetic disorders, this method has the potential to significantly improve the speed and precision of medical interventions for affected individuals.

What evidence suggests that Rapid Whole Genome Sequencing is effective for diagnosing genetic disorders?

Research shows that rapid whole genome sequencing (rWGS) can significantly improve the diagnosis of genetic conditions in children. In studies involving children in intensive care, 37% received a genetic diagnosis through rWGS, and 26% had their medical care adjusted as a result. This method quickly identifies problems and leads to better treatments. It also delivers diagnoses much faster than traditional methods, which is crucial in emergencies. By providing faster and more accurate results, rWGS can improve health outcomes and may reduce healthcare costs. ^{6 7 8 9 10}

Who Is on the Research Team?

David Dimmock, MD

Principal Investigator

Rady Pediatric Genomics & Systems Medicine Institute

Stephen Kingsmore

Principal Investigator

Rady Pediatric Genomics & Systems Medicine Institute

Are You a Good Fit for This Trial?

This trial is for acutely ill children suspected of having a genetic condition, with no restrictions on age, gender, race, or health. Preference is given to those under 4 months old and where diagnosis could change treatment. It includes symptomatic patients and their biological family members.

Inclusion Criteria

My doctor says my symptoms may be due to a genetic disorder.

I meet the study's inclusive criteria regarding age, gender, race, and health.

My child is under 4 months old, very sick, and might have a genetic condition.

Exclusion Criteria

Parents unable or unwilling to provide permission for participation

Involvement of child protective services unless child's life is in immediate danger and research holds out a prospect of direct benefit that is important to the health or well-being of the child

My condition is better suited for traditional genetic tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment and Sample Collection

Enrollment of healthy and affected subjects to collect samples and data for a pediatric genomic biorepository

Ongoing

Initial visit for sample collection

Genomic Sequencing and Analysis

Creation, analysis, and storage of genomic data from biological samples, including rWGS and other 'omic data

Within 30 days of enrollment

Return of Results and Clinical Utility Assessment

Return of genomic sequencing results and assessment of clinical utility by the subject's main provider

Within one month of the return of results

Follow-up

Participants are monitored for changes in clinical care and management following genetic diagnosis

Ongoing through study completion

What Are the Treatments Tested in This Trial?

Interventions

• Rapid Whole Genome Sequencing

Trial Overview The study tests Rapid Whole Genome Sequencing (rWGS) as a faster diagnostic tool compared to traditional methods for genetic conditions in children. It aims to assess diagnosis rates, impact on clinical care, and potential cost-effectiveness.

How Is the Trial Designed?

Group I: Enrollees Experimental Treatment 1 Intervention

Enrollment of healthy and affected subjects to collect samples and data for a pediatric genomic biorepository. Data includes genomic sequencing and resultant molecular diagnostic results, if any.

Who Is Running the Clinical Trial?

Rady Pediatric Genomics & Systems Medicine Institute

Lead Sponsor

Trials

10

Recruited

214,000+

Published Research Related to This Trial

Genomic sequencing can significantly enhance newborn screening programs by enabling rapid and accurate diagnoses of treatable rare diseases, which are major contributors to infant mortality and lifelong disabilities.

As large-scale genomic screening projects begin globally, it is crucial to generate evidence of their benefits while also addressing ethical, legal, and psychosocial challenges associated with this technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic newborn screening for rare diseases. Stark, Z., Scott, RH.[2023]

Rapid whole-genome sequencing (rWGS) for newborn screening (NBS) can identify a wide range of genetic disorders, with a high sensitivity of 88.8% and a negative predictive value of 99.6%, making it a promising tool for early diagnosis and intervention.

In a simulated study involving over 454,000 subjects, rWGS could have potentially prevented symptoms in critically ill newborns by diagnosing conditions that conventional NBS missed, highlighting its effectiveness in improving outcomes for genetic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases. Kingsmore, SF., Smith, LD., Kunard, CM., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10899612/

Rapid genomic sequencing for genetic disease diagnosis and ... In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03385876

Rapid Whole Genome Sequencing Study (rWGS) The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, and health economics including potential cost-effectiveness ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40310077/

Rapid Whole-Genome Sequencing in Critically Ill Infants ... The introduction of rapid whole-genome sequencing (rWGS) as a first-tier test in critically ill children with suspected, undiagnosed genetic diseases is a ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1098360024000029

Real-world diagnostic outcomes and cost-effectiveness of ... Using real-world data, we found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings.

5. nature.com nature.com/articles/s41525-018-0049-4

Rapid whole-genome sequencing decreases infant ... Rapid whole-genome sequencing (rWGS) provides a faster diagnosis, enabling precision medicine interventions in time to decrease the morbidity and mortality of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10336625/

Rapid Whole-Genomic Sequencing and a Targeted Neonatal ... This prospective multicenter study of 400 hospitalized infants with a suspected genetic disorder evaluated rates of molecular diagnostic yield, time to return ...

7. mdpi.com mdpi.com/2227-9067/12/4/429

Rapid Whole-Genome Sequencing in Critically Ill Infants ... This work aims to chronologically review significant clinical studies worldwide in pediatric genomic sequencing that have led to the development of rapid WGS ( ...

8. illumina.com illumina.com/science/genomics-research/articles/rapid-wgs-pipeline-optimized-for-speed-reproducibility-scalability.html

A rapid whole-genome sequencing pipeline optimized for ... A new, reengineered genome sequencing workflow for improved speed, reproducibility, and scalability, providing rWGS is 13.5 hours.

9. bmcmedgenomics.biomedcentral.com bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-024-01795-w

Whole genome sequencing in clinical practice The review provides an overview of WGS in clinical practice - describing the technology and current applications as well as challenges connected with data ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8970663/

Lessons learned: next-generation sequencing applied to ... Single-gene sequencing or gene panels are often used when specific diagnoses are suspected (e.g., neurofibromatosis, Noonan syndrome, or CHARGE ...