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

100000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Rapid Whole Genome Sequencing (rWGS) has proven to provide much faster diagnoses than traditional clinical testing, including clinical Whole Exome Sequencing (WES) and standard Whole Genome Sequencing (WGS). This collaborative study seeks to provide rWGS as a research test to additional pediatric hospitals nationwide to assist in the rapid diagnosis of acutely ill children suspected of a genetic condition. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, and health economics including potential cost-effectiveness of rWGS. This study will also serve as a biorepository for future research on samples and data generated from genomic sequencing.

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.

Is rapid whole genome sequencing (rWGS) safe for use in humans?

Rapid whole genome sequencing (rWGS) has been used safely in critically ill children to diagnose genetic disorders quickly, allowing for timely medical interventions. Studies have shown high accuracy and reliability in identifying genetic conditions, with no reported safety concerns in the process of sequencing itself. ^{1 2 3 4 5}

How does rapid whole genome sequencing differ from other treatments for genetic disorders?

Rapid whole genome sequencing (rWGS) is unique because it can quickly identify genetic variants causing disease, providing a diagnosis in as little as 13.5 hours, which is much faster than traditional methods. This speed allows for earlier and more precise treatment decisions, especially in critically ill patients, compared to standard genetic testing that can take much longer. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Rapid Whole Genome Sequencing for genetic disorders?

Rapid Whole Genome Sequencing (rWGS) has shown to be effective in diagnosing genetic diseases quickly, with a study demonstrating a 26-hour turnaround for a provisional diagnosis with high accuracy. It has also been shown to have a higher diagnostic yield compared to conventional genetic testing, identifying more genetic disorders in critically ill children, which can lead to timely and potentially life-saving interventions. ^{1 3 8 10 11}

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

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A 26-hour system of highly sensitive whole genome sequencing for emergency management of genetic diseases. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Periodic reanalysis of whole-genome sequencing data enhances the diagnostic advantage over standard clinical genetic testing. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Rapid Whole Genome Sequencing Diagnoses and Guides Treatment in Critically Ill Children in Belgium in Less than 40 Hours. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Massively parallel sequencing of ataxia genes after array-based enrichment. [2010]

8. England pubmed.ncbi.nlm.nih.gov

Genomic newborn screening for rare diseases. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Rapid Whole Genome Sequencing for Diagnosis of Single Locus Genetic Diseases in Critically Ill Children. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Rapid Targeted Genomics in Critically Ill Newborns. [2017]