Neonate WGS Testing for Genetic Disorders

(PISCES Trial)

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Jerry Vockley, MD, PhD

Disqualifiers: Known diagnosis, Major anomaly, Infection, others

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

Compensation: Varies

Number of Visits: 1

400 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the treatment Neonate WGS Testing for Genetic Disorders?

Research shows that whole genome sequencing (WGS) can diagnose genetic diseases in 57% of critically ill infants, allowing for early treatment changes that may improve outcomes. This rapid testing can be completed in as little as 26 hours, making it a valuable tool in managing genetic disorders in newborns. ^{1 2 3 4 5}

Is Neonate WGS Testing for Genetic Disorders safe for use in humans?

The research articles provided do not contain specific safety data for Neonate WGS Testing for Genetic Disorders. ^{6 7 8 9 10}

How is Neonate WGS Testing different from other treatments for genetic disorders in newborns?

Neonate WGS Testing is unique because it uses whole-genome sequencing to quickly and accurately diagnose genetic disorders in newborns, allowing for personalized treatment plans. This approach is faster and more comprehensive than traditional genetic tests, which often focus on specific genes or conditions. ^{2 3 11 12 13}

What is the purpose of this trial?

The purpose of this study is to understand how the use of whole genome sequencing (WGS) may be able to increase the speed with which a diagnosis is made for patients in an intensive care unit population. This is not an assessment of a new device, test, or technology. This project is an investigation of the utility of this technology in clinical care when compared to standard of care testing. The study will look at the ability to more quickly diagnose a patient (time to diagnosis and efficacy of testing) as compared to standard of care testing. The study will also look at the impact of WGS on patient outcomes and cost of clinical care.

Research Team

Gerard Vockley, MD, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for neonates in intensive care with suspected genetic disorders, over 24 weeks gestational age and weighing more than 600 grams. It's also open to their parents and necessary siblings. Neonates already diagnosed prenatally or with major congenital anomalies linked to chromosomal issues are excluded.

Inclusion Criteria

My parent or guardian has given formal consent for me to participate.

Neonates: Admitted to the intensive care unit at UPMC Children's Hospital (CHP) and/or Magee Women's Hospital

My newborn may have a genetic disorder, as suggested by their symptoms and tests, leading to a genetics consultation.

Exclusion Criteria

My newborn has a diagnosed condition from prenatal testing.

Neonates: Presence of documented significant congenital infection (e.g. congenital cytomegalovirus)

Siblings: Is not required for accurate interpretation of neonate results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection and Analysis

Neonate subjects undergo blood sampling for whole genome sequencing and bioinformatics analysis

Up to 4 years

1 visit (in-person) for sample collection

Genetic Counseling and Results Return

Pathogenic and likely-pathogenic variants are returned to the care team and parents in the setting of genetic counseling

Up to 4 years

Follow-up

Participants are monitored for changes in clinical management and outcomes after receiving WGS results

Up to 4 years

Treatment Details

Interventions

• Neonate WGS Testing

Trial Overview The study tests the effectiveness of whole genome sequencing (WGS) in diagnosing genetic conditions faster compared to standard testing in critically ill newborns. It will evaluate how WGS affects diagnosis time, patient outcomes, and healthcare costs.

Participant Groups

Group I: Neonate WGS Testing Experimental Treatment 1 Intervention

Neonate subjects who are eligible and whose parents consent to study will undergo blood sampling which will be sent for whole genome sequencing and bioinformatics analysis, filtering first a targeted panel of 1722 genes most likely to cause genetic disorders in the first year of life, and then with a whole exome filter if no obvious diagnosis is determined using the 1722 gene panel filter.

Who Is Running the Clinical Trial?

Jerry Vockley, MD, PhD

Lead Sponsor

Trials

6

Recruited

460+

Findings from Research

Whole-genome sequencing (WGS) significantly improved clinical management for acutely ill infants, with 21.1% of those receiving early results experiencing a change in management compared to only 10.3% in the delayed group, indicating a strong effect on treatment decisions.

The study involved 354 infants and showed that WGS not only provided a molecular diagnosis for more patients (31.0% in the early group vs 15.0% in the delayed group) but also has the potential to reduce healthcare disparities by offering equitable diagnostic access.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial. Krantz, ID., Medne, L., Weatherly, JM., et al.[2022]

A new trigger tool was developed using a random forest algorithm to effectively identify adverse events (AEs) in hospitalized neonates, based on data from 782 patients, achieving a sensitivity of 70.7% and specificity of 92.0.

In a validation study with 655 neonates, the tool identified 1172 unique AEs, with skin damage, iatrogenic diarrhea, and fever being the most common, demonstrating a positive predictive value of 0.686.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal Adverse Events' Trigger Tool Setup With Random Forest. Feng, K., Zhang, L., He, H., et al.[2023]

Implementing continuous incident reporting and prevention strategies led to a significant reduction in severe iatrogenic events in neonates, decreasing from 7.6 to 4.8 per 1000 patient-days over a two-year period.

Specific improvements included a notable drop in central catheter-related infections from 13.9 to 8.2 per 1000 catheter-days and a reduction in tenfold drug-dosing errors, although there was an increase in unplanned extubations from 5.6 to 15.5 per 1000 ventilation-days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iatrogenic events in neonates: beneficial effects of prevention strategies and continuous monitoring. Ligi, I., Millet, V., Sartor, C., et al.[2022]

Rapid whole-genome sequencing (WGS) can sequence an infant's genome in just 26 hours, enabling quick diagnosis and tailored management of genetic diseases.

This technology has the potential to reduce costs and minimize the time to diagnosis, which can alleviate pain and suffering for infants in the NICU, but it also raises important ethical considerations that need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethical Implications of Rapid Whole-Genome Sequencing in Neonates. Bell, SG.[2018]

References

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

Rapid whole genome sequencing and precision neonatology. [2022]

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

Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial. [2022]

3. Singapore pubmed.ncbi.nlm.nih.gov

The incorporation of next-generation sequencing into pediatric care. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Strategies in Rapid Genetic Diagnostics of Critically Ill Children: Experiences From a Dutch University Hospital. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Rapid genomic testing for critically ill children: time to become standard of care? [2023]

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

Neonatal Adverse Events' Trigger Tool Setup With Random Forest. [2023]

7. Colombia pubmed.ncbi.nlm.nih.gov

[Adverse drug reactions in neonates hospitalized in neonatal intensive care units in Barranquilla, Colombia]. [2018]

8. Italy pubmed.ncbi.nlm.nih.gov

[The use of RCGO triggers in the obstetric - gynecological procedures: the impact on the reduction of adeverse events. The experience of the Lombardia Region]. [2020]

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

Iatrogenic events in neonates: beneficial effects of prevention strategies and continuous monitoring. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Pregnancy exposure registries. [2018]

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

Genetic screening of newborns. [2009]

12. England pubmed.ncbi.nlm.nih.gov

Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders. [2021]

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

Ethical Implications of Rapid Whole-Genome Sequencing in Neonates. [2018]