Rapid Whole Genome Sequencing Study (rWGS)
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|ClinicalTrials.gov Identifier: NCT03385876|
Recruitment Status : Enrolling by invitation
First Posted : December 29, 2017
Last Update Posted : January 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Genetic Diseases Genetic Syndrome||Genetic: Genomic sequencing and molecular diagnostic results, if any||Not Applicable|
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Rapid Whole Genome Sequencing (rWGS) is a new technology that is able to deliver symptom-driven diagnoses of childhood-onset genetic diseases in as little as 26 hours. Investigators at RCIGM have shown that rWGS has higher diagnostic rates than traditional molecular testing in acutely ill infants suspected of a genetic diagnosis, with diagnostic rates up to 57%. Similarly, in the infant population, RCIGM researchers have shown that these diagnoses are useful in directing clinical care, with up to 70% of infants who receive a diagnosis having a subsequent change in management. In some cases, a timely diagnosis results in treatments that are lifesaving. RCIGM investigators have shown that up to 25% of infants who receive a diagnosis have a subsequent change in management that prevents morbidity. More data is needed to determine whether these results are found at other institutions, among other ethnic and racial groups, and in larger numbers of patients. More data is needed to examine the acute and long-term clinical utility of such testing, both in newborns and older children, as well as to determine the cost-effectiveness of this testing for other institutions. As such, this study will be a collaboration of multiple sites to share data and experiences of rWGS with the scientific community as well as hospital administrations, insurance companies and other key stakeholders who may be interested in promoting rWGS as a first-line clinical test in the future.
The study will provide clinical laboratory-confirmed results related to the affected patient's symptoms, including optional incidental findings unless subjects opt-out for these additional results, to allow for these research findings to be used in clinical care. Furthermore, this study will aggregate data regarding standard clinical genetic testing from multiple sites as well as cost measures to not only identify differences in diagnostic rates, diagnostic accuracy, and times to diagnoses, but to determine the cost-effectiveness of this testing and subsequent changes in care management. Clinical utility will be defined as changes in care that follow directly from results of genetic testing (both positive and negative), including standard clinical tests and rWGS. This data will be used to further examine the analytic, diagnostic, and clinical utility and cost-effectiveness of this testing.
rWGS methods continue to improve, and pediatric genomic medicine is a very new field of medical practice. This study will also inform investigators regarding best practices, both in terms of traditional medical outcomes and patient-centered outcomes. Consequently, this study will also act as a biorepository for samples and data as the ability to share genomic and phenotypic data amongst researchers is critical to progressing our understanding of the nascent field of pediatric genomic medicine.
- To collect biological samples and associated clinical data from acutely ill pediatric patients who may have a genetic disease and their family members (Phenome).
- To create, analyze and store genomic data from the biological samples. Genomic data will include genomic (gDNA) sequences, RNA sequences, and/or other related 'omic data (including, but not limited to, pharmacogenomics, transcriptomics, and epigenomics). Genomic data from rWGS will include single nucleotide calls (SNVs), structural variants such as copy number testing, genomic rearrangements, gene expression , the "whole transcriptome" or more limited DNA sequencing panels of specific genes or of all exons of genes (the "Exome").
- To evaluate the diagnosis rate of genetic diseases by rWGS in an acutely ill population enrolling from multiple sites with comparisons to standard clinical genetic testing.
- To assess the clinical utility of rapid genetic diagnoses in the care and management of patients.
- To examine the health economics and cost-effectiveness of this rapid testing across many sites.
- To investigate and improve genomics technologies and software to enhance understanding and testing abilities related to childhood diseases and potential treatment responses.
- To make specimens and data available for qualified researchers and collaborators to further the understanding of rare childhood diseases and treatment responses.
- To collect and correlate genomic data from a wide variety of populations and clinical presentations.
- To provide sample and data collections with uniform consent, methods of acquisition, storage for genome-based research studies with subsequent IRB approvals.
- To analyze and report clinically-confirmed genomic diagnoses and treatment guidance through use of new research technologies.
- To identify and study novel gene and disease processes.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100000 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Assignment|
|Masking:||None (Open Label)|
|Official Title:||Rapid Whole Genome Sequencing (rWGS): Rapid Genomic Sequencing for Acutely Ill Patients and the Collection, Storage, Analysis, and Distribution of Biological Samples, Genomic and Clinical Data|
|Actual Study Start Date :||August 29, 2017|
|Estimated Primary Completion Date :||December 31, 2050|
|Estimated Study Completion Date :||December 31, 2050|
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.
Genetic: Genomic sequencing and molecular diagnostic results, if any
Samples will be stored in the pediatric genomic biorepository. A subset of samples will undergo genetic/genomic analysis.
- Number of samples enrolled per year [ Time Frame: Yearly through study completion estimated to be 40 years. ]Establishment of a biorepository for genomic/precision medicine use in pediatric population. This will make samples available to study rare genetic disorders, screening methods, diagnostic methods, other "omics," and bench research for possible treatments.
- Proportion of children receiving molecular diagnoses [ Time Frame: Through study completion estimated to be 40 years. ]Utilize cutting edge technologies to improve both diagnostic rates and time to diagnosis for rare genetic diseases. Symptom driven return of results and analysis of clinical utility.
- Time taken to receive molecular diagnosis [ Time Frame: From date of enrollment until the date of documented clinical laboratory diagnosis or date of death from any cause, whichever came first, assessed up to 10 years. ]
- Proportion of children in which human phenotype ontology (HPO) terms accurately predict molecular diagnosis [ Time Frame: Through study completion estimated to be 40 years. ]
- Subject's main provider's perceived clinical utility of genomic sequencing [ Time Frame: Within one month of the return of results. ]Perceived utility/benefit of sequencing based on "Clinician Assessment" scale completed by patient's providers.
- Comparing diagnostic rates between singleton and trio analysis [ Time Frame: Within 30 days of enrollment. ]Marginal increase in diagnostic yield above singleton analysis based on the number of clinically confirmed diagnoses posted in medical record following singleton and trio levels of analysis in cases when both biological parents are available.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03385876
|United States, California|
|Rady Children's Institute for Genomic Medicine|
|San Diego, California, United States, 92123|
|United States, Florida|
|Nicklaus Children's Hospital|
|Miami, Florida, United States, 33155|
|Principal Investigator:||David Dimmock, MD||Rady Pediatric Genomics & Systems Medicine Institute|
|Study Director:||Stephen Kingsmore||Rady Pediatric Genomics & Systems Medicine Institute|