Rapid Whole Genome Sequencing for Rare Diseases

(MAGNET Trial)

Overseen By Stacey Pereira, PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Down syndrome, VACTERL, others

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

Compensation: Varies

Number of Visits: 2

410 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to provide advanced genetic testing and virtual consultations for very sick newborns in Texas hospitals, particularly near the Texas-Mexico border. Researchers are evaluating the effectiveness of a virtual consultation tool, called Consultagene, by gathering feedback from healthcare providers. The trial will employ rapid whole genome sequencing, a comprehensive genetic test, to help diagnose 200 infants over five years. Newborns who are very sick and likely have a genetic disorder, but remain undiagnosed, may be suitable candidates for this trial. As an unphased trial, it offers families a unique opportunity to access cutting-edge genetic testing and expert consultations to aid in diagnosing their newborns.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It is best to consult with the trial coordinators for specific guidance.

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

Research has shown that rapid whole genome sequencing (rWGS) offers a promising approach to diagnosing rare diseases, particularly in very sick infants. Studies have found this method to be highly useful in medical care and considered safe by participants.

Additional research supports that rWGS delivers diagnoses much faster than traditional testing methods, which is crucial for initiating treatment promptly. One study highlighted that this method results in fewer incorrect results, known as false positives.

Overall, evidence suggests that rWGS is well-tolerated and safe, with no significant negative effects reported in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Rapid whole genome sequencing is unique because it can quickly identify the genetic causes of rare diseases, which traditional diagnostic methods may miss or take much longer to uncover. Unlike standard genetic tests that might focus on specific genes or panels, this method analyzes the entire genome at once, providing a comprehensive genetic picture. Researchers are excited about this technique because it can lead to faster diagnosis and tailored treatments, significantly improving patient outcomes and potentially reducing the time and cost associated with finding a diagnosis.

What evidence suggests that rapid whole genome sequencing is effective for rare diseases?

Studies have shown that rapid whole genome sequencing (rWGS), which participants in this trial will receive, can diagnose genetic diseases much faster than traditional methods. In one study, 39% of patients received a diagnosis, and 27% had their treatment plans changed as a result. Another study found that early use of genome sequencing led to quicker diagnoses and reduced healthcare costs. Additionally, a specific screening method using genome sequencing reduced incorrect results by 97%. Overall, rWGS effectively identifies genetic conditions quickly, enabling timely and accurate medical decisions. ^{2 5 6 7 8}

Who Is on the Research Team?

Brendan Lee, MD, PhD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for seriously ill newborns in under-resourced hospitals in Texas, particularly near the Texas-Mexico border. It aims to identify genetic causes of birth defects through rapid whole genome sequencing.

Inclusion Criteria

My infant is suspected to have a genetic disorder and is under 3 months old.

Exclusion Criteria

Abnormal noninvasive prenatal testing (NIPT) suggesting chromosomal abnormality

Abnormal amniocentesis results

Abnormal newborn screening indicating an inborn error of metabolism

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Genetic Evaluation and Testing

Participants receive rapid whole genome sequencing and virtual genetic evaluations using video visits

1 week

2 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after genetic testing, including surveys and interviews

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Rapid whole genome sequencing

Trial Overview The study tests rapid whole genome sequencing on 200 infants over 5 years, assessing its effectiveness and the utility of a virtual consultation tool called Consultagene for healthcare providers.

How Is the Trial Designed?

Group I: MAGNET study patients Experimental Treatment 1 Intervention

Patients receiving rapid whole genome sequencing

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Human Genome Research Institute (NHGRI)

Collaborator

Trials

273

Recruited

299,000+

Citations

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

Rapid genomic sequencing for genetic disease diagnosis and ... The rate of diagnosis was 39% and results changed management in 27%. Further studies are needed to determine how clinical utility of URGS, RGS ...

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

Real-world diagnostic outcomes and cost-effectiveness of ... Drawing on real-world data from a Canadian health care system, we find that earlier access to genome-wide sequencing may generate more rapid diagnoses and cost ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03385876

Rapid Whole Genome Sequencing Study (rWGS) Rapid Whole Genome Sequencing (rWGS) has proven to provide much faster diagnoses than traditional clinical testing, including clinical Whole Exome ...

4. nature.com nature.com/articles/s41525-024-00396-x

Evidence review and considerations for use of first line ... Early use of genome sequencing (GS) in the diagnostic odyssey can reduce suffering and improve care, but questions remain about which patient populations are ...

5. radygenomics.org radygenomics.org/2024/beginngs-newborn-screening-by-genome-sequencing-shown-to-be-safe-and-effective-in-two-clinical-studies/

BeginNGS® Newborn Screening by Genome Sequencing ... The study reported a 97 percent reduction in false positives based on a method derived from human evolution. The genome variations that cause ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7675004/

An RCT of Rapid Genomic Sequencing among Seriously Ill ... An RCT of rapid genomic sequencing among seriously ill infants results in high clinical utility, changes in management, and low perceived harm.

7. 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 ... Rapid whole-genome sequencing (rWGS) is an alternative to standard genome sequencing, with the potential to offer fast and accurate diagnosis of rare genetic ...

8. hca.wa.gov hca.wa.gov/assets/program/WGS-final-report-2024.pdf

Whole Genome Sequencing: Final Evidence Report This evidence report is based on research conducted by the RTI–University of North Carolina. Evidence-based Practice Center through a ...