Genetic DiseaseNCT03458962
Diagnostic Odyssey: Whole Genome Sequencing (WGS)
An observational study of Genetic Disease and Genetic Syndrome, run by Nicklaus Children's Hospital f/k/a Miami Children's Hospital at 1 site in United States.
Trial summary
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology by understanding the potential value of Whole Genome Sequencing (WGS) in establishing genetic diagnosis. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Genetic Disease, Genetic Syndrome
- What is being tested?
- Genetic Enrollees
- How many people
- 1,000 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Feb 2018to 20 Feb 2070
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children from 0 to 21 years suffering from unknown diagnoses seen at Nicklaus Children's Hospital
Who may be able to join
- Symptomatic male or female children ages 0-21 who have un unknown medical condition thought to have an underlying genetic cause after parental consent has been obtained.
- Willingness of referring provider or other qualified medical staff member to participate in this study by facilitating collection of biologic specimens and clinical information.
- Patient whose medical condition can be reasonably attributed to a possible genetic etiology.
- Patient have had at least one diagnostic test without a definite diagnosis.
Who cannot join
- Unwillingness to consent to research.
- Affected adults (>21 years of age), unless they are a biological relative of the affected child.
- Any patient whose medical condition cannot be reasonably attributed to a possible genetic etiology or there is a prior diagnosis that explains the child's clinical presentation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Nickalus Children's Hospital f/k/a Miami Children's Hospital
Miami, Florida, 33155
About this study
Official title: Ending the Diagnostic Odyssey: Whole Genome Sequencing (WGS) to Identify Genetic Determinants of Previously Undiagnosed Disease in Children
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology by understanding the potential value of Whole Genome Sequencing (WGS) in establishing genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS and patient and provider experience with genomic medicine.
Read the detailed description
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology, in order to understand the potential value of WGS in establishing a genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS, and patient and provider experience with genomic medicine. Other clinical information of the type collected by treating physicians and stored in electronic medical records will also be collected to aid in the interpretation of laboratory data. Participants will also be asked to consent for future access of the medical record, future research on biospecimens and data generated from genomic sequencing, and for the ability to re-contact.
As part of this effort, Nicklaus Children's Hospital plans to create a large integrated database that contains the DNA sequences of the participants' whole human genomes and additional health information regarding characteristics and health of the persons whose samples have been sequenced. Scientists can then use the database to try to link those traits, diseases, and other conditions to changes in the sequence of the genome. Nicklaus Children's Hospital plans to make the database available to its collaborators, such as RCIGM, pharmaceutical and biotechnology companies, and other academic institutions which will use the database to find better, innovative ways to prevent, diagnose, and treat cancer and other diseases. De-identified data from this study will be shared with the community at-large, including publications and public databases. In addition, participants will be given the option to allow biospecimens (i.e., residual blood, saliva, CSF, etc.) to be included in biorepositories at Nicklaus Children's Hospital and Rady Pediatric Genomics \& Systems Medicine Institute (RCIGM).
The study will provide clinical laboratory-confirmed results related to the affected patient's phenotype, 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 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 WGS. This data will be used to further examine the analytic, diagnostic, and clinical utility and cost-effectiveness of this testing.
WGS 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.
Specific Aims:
- Use WGS to identify new genetic diagnoses in children with multiple congenital anomalies, developmental delay, autism, seizures, intellectual disabilities, neurodegenerative disorders, and metabolic illness.
- Evaluate the diagnosis rate of genetic diseases by WGS in previously undiagnosed patients.
- Assess the clinical utility of WGS in the care and management of patients.
- Examine the health economics and cost-effectiveness of WGS.
- Evaluate the provider, patient and family experience with genomic medicine
- Collect biological samples and associated clinical data from pediatric patients who may have a genetic disease and their family members (the "Phenome").
- 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 WGS will include single nucleotide variants (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").
- Analyze and report clinically-confirmed genomic diagnoses and treatment guidance through use of new research technologies.
- Identify and study novel gene and disease processes.
- Conditions
- Genetic Disease, Genetic Syndrome
- Being tested
- Genetic Enrollees
- Keywords
- Nicklaus Children's, Pediatric, Genomic, Precision Medicine, Biorepository, Rady Children's
- Medical subject headings
- Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic EnrolleesGenetic
Identification of new genetic diagnoses in children with multiple congenital anomalies, developmental delay, autism, seizures, intellectual disabilities, neurodegenerative disorders and metabolic illness. Samples and data will be stored in a pediatric biorepository. A subset of samples will undergo genetic/genomic analysis.
| Study group | Role | What they receive |
|---|---|---|
| Genetic Enrollees | Enrollment of patients for whom WGS may be beneficial. Patients who are ill and for whom a genetic diagnosis is suspected but not yet established. Receives: Genetic: Genetic Enrollees |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients enrolled per year
Total number of enrolled patients who will undergo WGS testing
Measured: Yearly throughout study completion up to 50 years
Secondary outcomes (4)
Diagnosis Rate of genetic diseases
Proportion of diagnosis rate of genetic diseases by WGS in previously undiagnosed patients
Measured: Throughout study completion up to 50 years
Clinical Utility
Total number of clinical utility of WGS in the case and management of patients
Measured: Throughout study completion up to 50 years
Phenome
Total number of biological samples and associated clinical data who have a genetic disease and their family members
Measured: Throughout study completion up to 50 years
Clinically-confirmed diagnoses
Proportion of clinically-confirmed genomic diagnoses and treatment guidance through the use of new research technologies
Measured: Throughout study completion up to 50 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start20 Feb 2018
- Primary completion20 Feb 2070 (estimated)
- Study completion20 Feb 2070 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Genetic DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicklaus Children's Hospital f/k/a Miami Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Rady Pediatric Genomics & Systems Medicine Institute
- Responsible party
- Sponsor
- Investigators
- Parul Jayakar, MD, Principal investigator, Nicklaus Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03458962
- Sponsor's protocol ID
- (WGS) Protocol #20172859
- Status last verified
- Aug 2026
- First submitted
- 2 Mar 2018
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McCandless SE, Brunger JW, Cassidy SB. The burden of genetic disease on inpatient care in a children's hospital. Am J Hum Genet. 2004 Jan;74(1):121-7. doi: 10.1086/381053. Epub 2003 Dec 12.
PubMed 14681831Sawyer SL, Hartley T, Dyment DA, Beaulieu CL, Schwartzentruber J, Smith A, Bedford HM, Bernard G, Bernier FP, Brais B, Bulman DE, Warman Chardon J, Chitayat D, Deladoey J, Fernandez BA, Frosk P, Geraghty MT, Gerull B, Gibson W, Gow RM, Graham GE, Green JS, Heon E, Horvath G, Innes AM, Jabado N, Kim RH, Koenekoop RK, Khan A, Lehmann OJ, Mendoza-Londono R, Michaud JL, Nikkel SM, Penney LS, Polychronakos C, Richer J, Rouleau GA, Samuels ME, Siu VM, Suchowersky O, Tarnopolsky MA, Yoon G, Zahir FR; FORGE Canada Consortium; Care4Rare Canada Consortium; Majewski J, Boycott KM. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016 Mar;89(3):275-84. doi: 10.1111/cge.12654. Epub 2015 Sep 22.
PubMed 26283276
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ending the Diagnostic Odyssey: Whole Genome Sequencing (WGS) to Identify Genetic Determinants of Previously Undiagnosed Disease in Children
- ClinicalTrials.gov ID
- NCT03458962
- Acronym / sponsor ID
- (WGS) Protocol #20172859
- Conditions
- Genetic Disease, Genetic Syndrome
- Keywords
- Nicklaus Children's, Pediatric, Genomic, Precision Medicine, Biorepository, Rady Children's
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Nicklaus Children's Hospital f/k/a Miami Children's HospitalUniversity, hospital or other
- Collaborators
- Rady Pediatric Genomics & Systems Medicine Institute
- Study start
- 20 Feb 2018 (actual)
- Primary completion
- 20 Feb 2070 (estimated)
- Study completion
- 20 Feb 2070 (estimated)
- First posted
- 8 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology by understanding the potential value of Whole Genome Sequencing (WGS) in establishing genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS and patient and provider experience with genomic medicine.
Detailed description
The goal of this collaborative research is to study human genomes in children with suspected congenital disease, multiple-congenital anomalies and/or multi-organ disease of unknown etiology, in order to understand the potential value of WGS in establishing a genetic diagnosis. The study will examine diagnosis rates, changes in clinical care as a result of a genetic diagnosis, health economics including potential cost-effectiveness of WGS, and patient and provider experience with genomic medicine. Other clinical information of the type collected by treating physicians and stored in electronic medical records will also be collected to aid in the interpretation of laboratory data. Participants will also be asked to consent for future access of the medical record, future research on biospecimens and data generated from genomic sequencing, and for the ability to re-contact.
As part of this effort, Nicklaus Children's Hospital plans to create a large integrated database that contains the DNA sequences of the participants' whole human genomes and additional health information regarding characteristics and health of the persons whose samples have been sequenced. Scientists can then use the database to try to link those traits, diseases, and other conditions to changes in the sequence of the genome. Nicklaus Children's Hospital plans to make the database available to its collaborators, such as RCIGM, pharmaceutical and biotechnology companies, and other academic institutions which will use the database to find better, innovative ways to prevent, diagnose, and treat cancer and other diseases. De-identified data from this study will be shared with the community at-large, including publications and public databases. In addition, participants will be given the option to allow biospecimens (i.e., residual blood, saliva, CSF, etc.) to be included in biorepositories at Nicklaus Children's Hospital and Rady Pediatric Genomics \& Systems Medicine Institute (RCIGM).
The study will provide clinical laboratory-confirmed results related to the affected patient's phenotype, 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 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 WGS. This data will be used to further examine the analytic, diagnostic, and clinical utility and cost-effectiveness of this testing.
WGS 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.
Specific Aims:
- Use WGS to identify new genetic diagnoses in children with multiple congenital anomalies, developmental delay, autism, seizures, intellectual disabilities, neurodegenerative disorders, and metabolic illness.
- Evaluate the diagnosis rate of genetic diseases by WGS in previously undiagnosed patients.
- Assess the clinical utility of WGS in the care and management of patients.
- Examine the health economics and cost-effectiveness of WGS.
- Evaluate the provider, patient and family experience with genomic medicine
- Collect biological samples and associated clinical data from pediatric patients who may have a genetic disease and their family members (the "Phenome").
- 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 WGS will include single nucleotide variants (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").
- Analyze and report clinically-confirmed genomic diagnoses and treatment guidance through use of new research technologies.
- Identify and study novel gene and disease processes.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Genetic Enrollees | – | Genetic: Genetic EnrolleesEnrollment of patients for whom WGS may be beneficial. Patients who are ill and for whom a genetic diagnosis is suspected but not yet established. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children from 0 to 21 years suffering from unknown diagnoses seen at Nicklaus Children's Hospital
Key inclusion criteria (4 listed)
- Symptomatic male or female children ages 0-21 who have un unknown medical condition thought to have an underlying genetic cause after parental consent has been obtained.
- Willingness of referring provider or other qualified medical staff member to participate in this study by facilitating collection of biologic specimens and clinical information.
- Patient whose medical condition can be reasonably attributed to a possible genetic etiology.
- Patient have had at least one diagnostic test without a definite diagnosis.
Key exclusion criteria (3 listed)
- Unwillingness to consent to research.
- Affected adults (>21 years of age), unless they are a biological relative of the affected child.
- Any patient whose medical condition cannot be reasonably attributed to a possible genetic etiology or there is a prior diagnosis that explains the child's clinical presentation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genetic EnrolleesIdentification of new genetic diagnoses in children with multiple congenital anomalies, developmental delay, autism, seizures, intellectual disabilities, neurodegenerative disorders and metabolic illness. Samples and data will be stored in a pediatric biorepository. A subset of samples will undergo genetic/genomic analysis. | Genetic | Genetic Enrollees |
Primary outcome
Number of patients enrolled per year
Time frame: Yearly throughout study completion up to 50 years
Total number of enrolled patients who will undergo WGS testing
4 secondary outcomes
Diagnosis Rate of genetic diseases
Time frame: Throughout study completion up to 50 years
Clinical Utility
Time frame: Throughout study completion up to 50 years
Phenome
Time frame: Throughout study completion up to 50 years
Clinically-confirmed diagnoses
Time frame: Throughout study completion up to 50 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Background: PubMed 14681831McCandless SE, Brunger JW, Cassidy SB. The burden of genetic disease on inpatient care in a children's hospital. Am J Hum Genet. 2004 Jan;74(1):121-7. doi: 10.1086/381053. Epub 2003 Dec 12.
- Background: PubMed 26283276Sawyer SL, Hartley T, Dyment DA, Beaulieu CL, Schwartzentruber J, Smith A, Bedford HM, Bernard G, Bernier FP, Brais B, Bulman DE, Warman Chardon J, Chitayat D, Deladoey J, Fernandez BA, Frosk P, Geraghty MT, Gerull B, Gibson W, Gow RM, Graham GE, Green JS, Heon E, Horvath G, Innes AM, Jabado N, Kim RH, Koenekoop RK, Khan A, Lehmann OJ, Mendoza-Londono R, Michaud JL, Nikkel SM, Penney LS, Polychronakos C, Richer J, Rouleau GA, Samuels ME, Siu VM, Suchowersky O, Tarnopolsky MA, Yoon G, Zahir FR; FORGE Canada Consortium; Care4Rare Canada Consortium; Majewski J, Boycott KM. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016 Mar;89(3):275-84. doi: 10.1111/cge.12654. Epub 2015 Sep 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Parul Jayakar, MD principal investigator
Nicklaus Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Genetic Disease and Genetic Syndrome, run by Nicklaus Children's Hospital f/k/a Miami Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients enrolled per year (time frame: Yearly throughout study completion up to 50 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03458962, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.