Genetic DiseasesNSIGHT2NCT03211039
Perinatal Precision Medicine
A study testing Genomic sequencing and molecular diagnostic results, if any. in people with Genetic Diseases and Genetic Syndrome, run by Rady Pediatric Genomics & Systems Medicine Institute at 1 site in United States.
Trial summary
This study will seek to determine if rapid genomic sequencing improves outcomes for acutely ill infants. The investigator will enroll up to 1,000 acutely ill infants in a prospective, randomized, blinded study to either rapid Whole Genome Sequencing (WGS) or rapid Whole Exome Sequencing (WES, which is 2% of the genome… Read more about this study
- Who is it for?
- Ages Up to 4 months
- Conditions the study is for
- Genetic Diseases, Genetic Syndrome, Mendelian Disorders
- What is being tested?
- Genomic sequencing and molecular diagnostic results, if any.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 213 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2017to 30 Jul 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Individual in whom one of the following criteria is met:
- Acutely ill inpatient of less than 4 months of age and within 96 hours of admission.
- Acutely ill inpatient of less than 4 months of age and within 96 hours of development of an abnormal response to standard therapy for an underlying condition.
- Acutely ill inpatient of less than 4 months of age and within 96 hours of development of clinical feature or laboratory test value suggestive of a genetic condition.
- Biological relative of an infant enrolled in this study.
Who cannot join
- Inpatients of greater than 4 months of age, or who do not meet any of the inclusion criteria, or with:
- Neonatal infection or sepsis with normal response to therapy
- Isolated prematurity
- Isolated unconjugated hyperbilirubinemia
- Hypoxic Ischemic Encephalopathy with clear precipitating event
- Previously confirmed genetic diagnosis that explains their clinical condition (i.e. have a positive genetic test)
Show all 9Show fewer
- Isolated Transient Neonatal Tachypnea
- Permission is unable to be obtained by a legal guardian or court-appointed representative within 96 hours of becoming eligible for enrollment.
- Non-viable neonates - newborns less than 28 days of life with a modified code status (only full code patients may be enrolled).
Trial locations and contacts
1 site in 1 country.
United States1 site
Rady Children's Institute for Genomic Medicine (RCIGM)
San Diego, California, 92123
About this study
Official title: Prenatal Precision Medicine (NSIGHT2): A Randomized, Blinded, Prospective Study of the Clinical Utility of Rapid Genomic Sequencing for Infants in the Acute-care Setting
This study will seek to determine if rapid genomic sequencing improves outcomes for acutely ill infants. The investigator will enroll up to 1,000 acutely ill infants in a prospective, randomized, blinded study to either rapid Whole Genome Sequencing (WGS) or rapid Whole Exome Sequencing (WES, which is 2% of the genome and ~4-fold less expensive). 213 infants were actually enrolled. Outcomes will be measured both by objective clinical measures and family perceptions (patient/family centered outcomes). Primary analysis of WGS or WES will be in infants alone. Secondary analysis, in infants who do not receive a diagnosis, will be of families - ideally trios (mother, father, and affected infant), which is ~2-fold more expensive. Trios will be analyzed within the same randomization arm (WGS or WES). This study is designed to quantify which acutely ill infants benefit from rapid genomic sequencing, by how much they benefit, how they benefit, which rapid genomic sequencing method is superior, and the cost effectiveness of such testing.
Read the detailed description
Acutely ill infant inpatients who have an undiagnosed illness, and their families, will be eligible to participate in the study. The investigators will enroll up to 1,000 infants. Locally, the study population will be recruited from Rady Children's Hospital (RCH) inpatient population, primarily the neonatal intensive care unit (NICU), pediatric intensive care unit (PICU), and cardiovascular intensive care unit (CVICU), with a smaller population presenting to other hospital in-patient services. Recruitment will be targeted at the RCH main campus, but it may include referrals from satellite locations in the RCH network (particularly the RCH NICU network throughout San Diego County). All patients will continue to receive routine care as clinically indicated, including the state newborn screen and other genetic testing as determined by their treating providers. Half of the affected study participants will be randomized to receive rapid whole genome sequencing (WGS) and the other half will receive rapid whole exome sequencing (WES). Each arm will initially be analyzed using the patient's (proband's) sample only. If a proband-only analysis fails to yield a diagnosis, genomic data from the biological family members (typically parents), when available, will be used to supplement analysis (trio analysis). Occasionally, a second affected sibling may be available for family analysis. Not infrequently, the father is not available for study. Similarly, the investigators anticipate the need for targeted genetic analysis of biological parents, and possibly other family members, to confirm diagnostic results and/or provide additional information regarding inheritance.
The investigators anticipate that in rare cases a newborn may be so ill that the team lacks equipoise that the child can wait for the estimated ten day turnaround time of our send-out exome testing. In these rare cases, the PI, or his delegate, will decide if the child is not eligible for randomization. These children will remain in the research study throughout the entirety of the study, but will receive in-house ultra-rapid whole genome sequencing by the Rady Children's Institute for Genomic Medicine (RCIGM, also called RadyPGSMI) laboratory in lieu of either a rapid genome or rapid exome (both anticipated to be 10 day turn-arounds).
Enrollment will be sought within the first 96 hours following admission to RCH or an RCH network ICU or within 96 hours of meeting criteria for the study if the infant was not previously eligible. Patients and their family members who consent to participate will have their blood drawn and will be randomized to receive either rapid WGS or rapid WES. The initial symptom-driven analysis will be conducted on the patient's sample only (singleton analysis). If a diagnosis is not found promptly (within 24 hours) via a singleton analysis, the family (or any combination of parents and/or other family members) will be analyzed using the same technology that the patient was randomized to receive. Pathogenic and likely pathogenic variants (as determined by American College of Medical Genetics (ACMG) guidelines) that relate in part or in whole to the patient's current phenotype will be clinically confirmed and reported into the patients' medical record. Although the intention of the study is to return symptom-driven results to the medical record, the clinical report for confirmation of symptom-driven findings may include negative findings of testing. In the event that our analysis incidentally finds a pathogenic variant for which a treatment or intervention exists to improve morbidity and/or mortality, families may choose not to receive this additional information.
- Conditions
- Genetic Diseases, Genetic Syndrome, Mendelian Disorders
- Being tested
- Genomic sequencing and molecular diagnostic results, if any.
- Keywords
- Neonate, Genomic Medicine, Rapid Precision Medicine, Rapid Whole Genome Sequencing, Diagnosis, Infant, Intensive care unit, clinical trial, Rapid Whole Exome Sequencing, Single locus disease, Ultra-rapid whole genome sequencing, Clinical Utility
- Medical subject headings
- Genetic Diseases, Inborn, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genomic sequencing and molecular diagnostic results, if any.Genetic
Patients and their families will be randomized to either receive whole genome sequencing or whole exome sequencing.
| Study group | Role | What they receive |
|---|---|---|
| Whole Genome Sequencing | Other | Genetic test that looks at all coding and non-coding areas of the genome Receives: Genetic: Genomic sequencing and molecular diagnostic results, if any. |
| Whole Exome Sequencing | Other | Genetic test that looks at all coding areas of the genome Receives: Genetic: Genomic sequencing and molecular diagnostic results, if any. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subject's Main Provider's Perceived Clinical Utility of Genomic Sequencing
Perceived utility/benefit of sequencing based on "Clinician Assessment" questionnaire completed by patient's providers. Question: Was the test clinically useful? Response was measured on a 5-point Likert scale (very useful=5, useful=4, neutral=3, not very useful=2, not useful at all=1.
Measured: Within one week of the return of results
Test Results Led to Change in Patient Management
Test results led to Change in clinical management (select all that apply):
- Surgical intervention added
- Surgical intervention removed
- Surgical intervention changed
- Medication added
- Medication removed
- Medication changed
- Diet changed
- New specialty service sought
- Prior specialty service no longer required
- New imaging sought
- Prior imaging cancelled
- New test ordered
- Prior testing cancelled
- Screening for additional comorbidities added
- Screening for additional comorbidities removed
- Palliative care initiated
- Palliative care withdrawn
- Other: (text box for written description)
Measured: Within 1 week of return of results
Test Led to Changes in Management That Altered Patient Outcome
Primary physician perception of change in outcome
Measured: 1 year
Secondary outcomes (5)
Diagnostic Proportion for Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES)
WGS and WES are two clinical diagnostic test modalities. Results of testing were placed in the electronic medical record. Results either provided a molecular diagnosis that explained the patient's condition or did not. The diagnostic proportion is the number of patients who received a molecular diagnosis by the test modality divided by the total number of patients who were tested by that modality.
Measured: Within approximately 30 days of enrollment
Result Within 7 Days of Sample Receipt
Time to result.
Measured: Within 7 days of sample receipt
Parental Perceived Usefulness of Test
Parental perception that test was useful
Measured: Within one week of the return of results and approximately one year after enrollment
Parental Perception of Test Benefit for Their Infant
Parental perception that the test benefitted their infant
Measured: Within one week of the return of results and approximately one year after enrollment
Parental Decisional Regret With Sequencing
Markers of harm in genetic diagnosis as evidenced by Brehaut's Decisional Regret scale. Scale 0-100. Higher scores indicate higher regret.
Measured: Within one week of the return of results and approximately one year after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2017
- Study start29 Jun 2017
- Primary completion9 Oct 2018
- Study completion30 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Genetic DiseasesStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The initial symptom-driven analysis will be conducted on the patient's (NICU infants) sample only (singleton analysis). Patients will be randomized to receive either whole genome sequencing or whole exome sequencing. If a diagnosis is not found promptly (within 24 hours) via singleton analysis, sequential analysis of the family (or any combination of parents and/or other family members) will be analyzed using the same technology that the patient was randomized to receive. The study includes parental and physician questionnaires to understand perceptions regarding testing. There is no randomization of parents or physicians nor a requirement to respond to the questionnaires for the patient (NICU infant) to participate in the study. Enrollment: 213 patients (NICU infants)
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rady Pediatric Genomics & Systems Medicine Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI)
- Responsible party
- Principal investigator, Stephen F. Kingsmore, Rady Pediatric Genomics & Systems Medicine Institute
- Investigators
- Stephen F Kingsmore, MD, DSc, Principal investigator, Rady Pediatric Genomics & Systems Medicine Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211039
- Sponsor's protocol ID
- 161983
- Other IDs
- U19HD077693
- Acronym
- NSIGHT2
- Status last verified
- Feb 2024
- First submitted
- 24 May 2017
- Last updated
- 1 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Samples and data may be shared confidentially with collaborators, such as commercial laboratories or technology companies. All data and sample sharing will be strictly confidential. No identifying information will be shared.
Publications
Milko LV, Chen F, Chan K, Brower AM, Agrawal PB, Beggs AH, Berg JS, Brenner SE, Holm IA, Koenig BA, Parad RB, Powell CM, Kingsmore SF. FDA oversight of NSIGHT genomic research: the need for an integrated systems approach to regulation. NPJ Genom Med. 2019 Dec 10;4:32. doi: 10.1038/s41525-019-0105-8. eCollection 2019.
PubMed 31839987Kingsmore SF, Nofsinger R, Ellsworth K. Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review. NPJ Genom Med. 2024 Feb 27;9(1):17. doi: 10.1038/s41525-024-00404-0.
PubMed 38413639Chan K, Hu Z, Bush LW, Cope H, Holm IA, Kingsmore SF, Wilhelm K, Scharfe C, Brower A. NBSTRN Tools to Advance Newborn Screening Research and Support Newborn Screening Stakeholders. Int J Neonatal Screen. 2023 Oct 30;9(4):63. doi: 10.3390/ijns9040063.
PubMed 37987476Owen MJ, Lefebvre S, Hansen C, Kunard CM, Dimmock DP, Smith LD, Scharer G, Mardach R, Willis MJ, Feigenbaum A, Niemi AK, Ding Y, Van Der Kraan L, Ellsworth K, Guidugli L, Lajoie BR, McPhail TK, Mehtalia SS, Chau KK, Kwon YH, Zhu Z, Batalov S, Chowdhury S, Rego S, Perry J, Speziale M, Nespeca M, Wright MS, Reese MG, De La Vega FM, Azure J, Frise E, Rigby CS, White S, Hobbs CA, Gilmer S, Knight G, Oriol A, Lenberg J, Nahas SA, Perofsky K, Kim K, Carroll J, Coufal NG, Sanford E, Wigby K, Weir J, Thomson VS, Fraser L, Lazare SS, Shin YH, Grunenwald H, Lee R, Jones D, Tran D, Gross A, Daigle P, Case A, Lue M, Richardson JA, Reynders J, Defay T, Hall KP, Veeraraghavan N, Kingsmore SF. An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases. Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6.
PubMed 35882841Kingsmore SF, Cole FS. The Role of Genome Sequencing in Neonatal Intensive Care Units. Annu Rev Genomics Hum Genet. 2022 Aug 31;23:427-448. doi: 10.1146/annurev-genom-120921-103442. Epub 2022 Jun 8.
PubMed 35676073Dimmock DP, Clark MM, Gaughran M, Cakici JA, Caylor SA, Clarke C, Feddock M, Chowdhury S, Salz L, Cheung C, Bird LM, Hobbs C, Wigby K, Farnaes L, Bloss CS, Kingsmore SF; RCIGM Investigators. An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm. Am J Hum Genet. 2020 Nov 5;107(5):942-952. doi: 10.1016/j.ajhg.2020.10.003.
PubMed 33157007Cakici JA, Dimmock DP, Caylor SA, Gaughran M, Clarke C, Triplett C, Clark MM, Kingsmore SF, Bloss CS. A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants. Am J Hum Genet. 2020 Nov 5;107(5):953-962. doi: 10.1016/j.ajhg.2020.10.004.
PubMed 33157008Kingsmore SF, Cakici JA, Clark MM, Gaughran M, Feddock M, Batalov S, Bainbridge MN, Carroll J, Caylor SA, Clarke C, Ding Y, Ellsworth K, Farnaes L, Hildreth A, Hobbs C, James K, Kint CI, Lenberg J, Nahas S, Prince L, Reyes I, Salz L, Sanford E, Schols P, Sweeney N, Tokita M, Veeraraghavan N, Watkins K, Wigby K, Wong T, Chowdhury S, Wright MS, Dimmock D; RCIGM Investigators. A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants. Am J Hum Genet. 2019 Oct 3;105(4):719-733. doi: 10.1016/j.ajhg.2019.08.009. Epub 2019 Sep 26.
PubMed 31564432Cakici JA, Dimmock D, Caylor S, Gaughran M, Clarke C, Triplett C, Clark MM, Kingsmore SF, Bloss CS. Assessing Diversity in Newborn Genomic Sequencing Research Recruitment: Race/Ethnicity and Primary Spoken Language Variation in Eligibility, Enrollment, and Reasons for Declining. Clin Ther. 2023 Aug;45(8):736-744. doi: 10.1016/j.clinthera.2023.06.014. Epub 2023 Jul 8.
PubMed 37429778Owen MJ, Batalov S, Ellsworth KA, Wright M, Breeding S, Hugh K, Kingsmore SF, Ding Y. Rapid Whole Genome Sequencing for Diagnosis of Single Locus Genetic Diseases in Critically Ill Children. Methods Mol Biol. 2023;2621:217-239. doi: 10.1007/978-1-0716-2950-5_12.
PubMed 37041447Laurenzano SE, McFall C, Nguyen L, Savla D, Coufal NG, Wright MS, Tokita M, Dimmock D, Kingsmore SF, Newfield RS. Neonatal diabetes mellitus due to a novel variant in the INS gene. Cold Spring Harb Mol Case Stud. 2019 Aug 1;5(4):a004085. doi: 10.1101/mcs.a004085. Print 2019 Aug.
PubMed 31196892
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prenatal Precision Medicine (NSIGHT2): A Randomized, Blinded, Prospective Study of the Clinical Utility of Rapid Genomic Sequencing for Infants in the Acute-care Setting
- ClinicalTrials.gov ID
- NCT03211039
- Acronym / sponsor ID
- NSIGHT2 / 161983
- Conditions
- Genetic Diseases, Genetic Syndrome, Mendelian Disorders
- Keywords
- Neonate, Genomic Medicine, Rapid Precision Medicine, Rapid Whole Genome Sequencing, Diagnosis, Infant, Intensive care unit, clinical trial
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Rady Pediatric Genomics & Systems Medicine InstituteUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI)
- Study start
- 29 Jun 2017 (actual)
- Primary completion
- 9 Oct 2018 (actual)
- Study completion
- 30 Jul 2024 (estimated)
- First posted
- 7 Jul 2017 (actual)
- Results
- Posted 27 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will seek to determine if rapid genomic sequencing improves outcomes for acutely ill infants. The investigator will enroll up to 1,000 acutely ill infants in a prospective, randomized, blinded study to either rapid Whole Genome Sequencing (WGS) or rapid Whole Exome Sequencing (WES, which is 2% of the genome and ~4-fold less expensive). 213 infants were actually enrolled. Outcomes will be measured both by objective clinical measures and family perceptions (patient/family centered outcomes). Primary analysis of WGS or WES will be in infants alone. Secondary analysis, in infants who do not receive a diagnosis, will be of families - ideally trios (mother, father, and affected infant), which is ~2-fold more expensive. Trios will be analyzed within the same randomization arm (WGS or WES). This study is designed to quantify which acutely ill infants benefit from rapid genomic sequencing, by how much they benefit, how they benefit, which rapid genomic sequencing method is superior, and the cost effectiveness of such testing.
Detailed description
Acutely ill infant inpatients who have an undiagnosed illness, and their families, will be eligible to participate in the study. The investigators will enroll up to 1,000 infants. Locally, the study population will be recruited from Rady Children's Hospital (RCH) inpatient population, primarily the neonatal intensive care unit (NICU), pediatric intensive care unit (PICU), and cardiovascular intensive care unit (CVICU), with a smaller population presenting to other hospital in-patient services. Recruitment will be targeted at the RCH main campus, but it may include referrals from satellite locations in the RCH network (particularly the RCH NICU network throughout San Diego County). All patients will continue to receive routine care as clinically indicated, including the state newborn screen and other genetic testing as determined by their treating providers. Half of the affected study participants will be randomized to receive rapid whole genome sequencing (WGS) and the other half will receive rapid whole exome sequencing (WES). Each arm will initially be analyzed using the patient's (proband's) sample only. If a proband-only analysis fails to yield a diagnosis, genomic data from the biological family members (typically parents), when available, will be used to supplement analysis (trio analysis). Occasionally, a second affected sibling may be available for family analysis. Not infrequently, the father is not available for study. Similarly, the investigators anticipate the need for targeted genetic analysis of biological parents, and possibly other family members, to confirm diagnostic results and/or provide additional information regarding inheritance.
The investigators anticipate that in rare cases a newborn may be so ill that the team lacks equipoise that the child can wait for the estimated ten day turnaround time of our send-out exome testing. In these rare cases, the PI, or his delegate, will decide if the child is not eligible for randomization. These children will remain in the research study throughout the entirety of the study, but will receive in-house ultra-rapid whole genome sequencing by the Rady Children's Institute for Genomic Medicine (RCIGM, also called RadyPGSMI) laboratory in lieu of either a rapid genome or rapid exome (both anticipated to be 10 day turn-arounds).
Enrollment will be sought within the first 96 hours following admission to RCH or an RCH network ICU or within 96 hours of meeting criteria for the study if the infant was not previously eligible. Patients and their family members who consent to participate will have their blood drawn and will be randomized to receive either rapid WGS or rapid WES. The initial symptom-driven analysis will be conducted on the patient's sample only (singleton analysis). If a diagnosis is not found promptly (within 24 hours) via a singleton analysis, the family (or any combination of parents and/or other family members) will be analyzed using the same technology that the patient was randomized to receive. Pathogenic and likely pathogenic variants (as determined by American College of Medical Genetics (ACMG) guidelines) that relate in part or in whole to the patient's current phenotype will be clinically confirmed and reported into the patients' medical record. Although the intention of the study is to return symptom-driven results to the medical record, the clinical report for confirmation of symptom-driven findings may include negative findings of testing. In the event that our analysis incidentally finds a pathogenic variant for which a treatment or intervention exists to improve morbidity and/or mortality, families may choose not to receive this additional information.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The initial symptom-driven analysis will be conducted on the patient's (NICU infants) sample only (singleton analysis). Patients will be randomized to receive either whole genome sequencing or whole exome sequencing. If a diagnosis is not found promptly (within 24 hours) via singleton analysis, sequential analysis of the family (or any combination of parents and/or other family members) will be analyzed using the same technology that the patient was randomized to receive. The study includes parental and physician questionnaires to understand perceptions regarding testing. There is no randomization of parents or physicians nor a requirement to respond to the questionnaires for the patient (NICU infant) to participate in the study. Enrollment: 213 patients (NICU infants)
| Arm | Type | Receives |
|---|---|---|
| Whole Genome Sequencing | Other | Genetic: Genomic sequencing and molecular diagnostic results, if any.Genetic test that looks at all coding and non-coding areas of the genome |
| Whole Exome Sequencing | Other | Genetic: Genomic sequencing and molecular diagnostic results, if any.Genetic test that looks at all coding areas of the genome |
Who may qualify
- Ages
- Up to 4 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Acutely ill inpatient of less than 4 months of age and within 96 hours of admission.
- Acutely ill inpatient of less than 4 months of age and within 96 hours of development of an abnormal response to standard therapy for an underlying condition.
- Acutely ill inpatient of less than 4 months of age and within 96 hours of development of clinical feature or laboratory test value suggestive of a genetic condition.
- Biological relative of an infant enrolled in this study.
Key exclusion criteria (9 listed)
- Inpatients of greater than 4 months of age, or who do not meet any of the inclusion criteria, or with:
- Neonatal infection or sepsis with normal response to therapy
- Isolated prematurity
- Isolated unconjugated hyperbilirubinemia
- Hypoxic Ischemic Encephalopathy with clear precipitating event
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 |
|---|---|---|
| Genomic sequencing and molecular diagnostic results, if any.Patients and their families will be randomized to either receive whole genome sequencing or whole exome sequencing. | Genetic | Whole Exome Sequencing, Whole Genome Sequencing |
Primary outcome
Subject's Main Provider's Perceived Clinical Utility of Genomic Sequencing
Time frame: Within one week of the return of results
Perceived utility/benefit of sequencing based on "Clinician Assessment" questionnaire completed by patient's providers. Question: Was the test clinically useful? Response was measured on a 5-point Likert scale (very useful=5, useful=4, neutral=3, not very useful=2, not useful at all=1.
Test Results Led to Change in Patient Management
Time frame: Within 1 week of return of results
Test results led to Change in clinical management (select all that apply): * Surgical intervention added * Surgical intervention removed * Surgical intervention changed * Medication added * Medication removed * Medication changed * Diet changed * New specialty service sought * Prior specialty service no longer required * New imaging sought * Prior imaging cancelled * New test ordered * Prior testing cancelled * Screening for additional comorbidities added * Screening for additional comorbidities removed * Palliative care initiated * Palliative care withdrawn * Other: (text box for written description)
Test Led to Changes in Management That Altered Patient Outcome
Time frame: 1 year
Primary physician perception of change in outcome
5 secondary outcomes
Diagnostic Proportion for Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES)
Time frame: Within approximately 30 days of enrollment
Result Within 7 Days of Sample Receipt
Time frame: Within 7 days of sample receipt
Parental Perceived Usefulness of Test
Time frame: Within one week of the return of results and approximately one year after enrollment
Parental Perception of Test Benefit for Their Infant
Time frame: Within one week of the return of results and approximately one year after enrollment
Parental Decisional Regret With Sequencing
Time frame: Within one week of the return of results and approximately one year after enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31839987Milko LV, Chen F, Chan K, Brower AM, Agrawal PB, Beggs AH, Berg JS, Brenner SE, Holm IA, Koenig BA, Parad RB, Powell CM, Kingsmore SF. FDA oversight of NSIGHT genomic research: the need for an integrated systems approach to regulation. NPJ Genom Med. 2019 Dec 10;4:32. doi: 10.1038/s41525-019-0105-8. eCollection 2019.
- Background: PubMed 38413639Kingsmore SF, Nofsinger R, Ellsworth K. Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review. NPJ Genom Med. 2024 Feb 27;9(1):17. doi: 10.1038/s41525-024-00404-0.
- Background: PubMed 37987476Chan K, Hu Z, Bush LW, Cope H, Holm IA, Kingsmore SF, Wilhelm K, Scharfe C, Brower A. NBSTRN Tools to Advance Newborn Screening Research and Support Newborn Screening Stakeholders. Int J Neonatal Screen. 2023 Oct 30;9(4):63. doi: 10.3390/ijns9040063.
- Background: PubMed 35882841Owen MJ, Lefebvre S, Hansen C, Kunard CM, Dimmock DP, Smith LD, Scharer G, Mardach R, Willis MJ, Feigenbaum A, Niemi AK, Ding Y, Van Der Kraan L, Ellsworth K, Guidugli L, Lajoie BR, McPhail TK, Mehtalia SS, Chau KK, Kwon YH, Zhu Z, Batalov S, Chowdhury S, Rego S, Perry J, Speziale M, Nespeca M, Wright MS, Reese MG, De La Vega FM, Azure J, Frise E, Rigby CS, White S, Hobbs CA, Gilmer S, Knight G, Oriol A, Lenberg J, Nahas SA, Perofsky K, Kim K, Carroll J, Coufal NG, Sanford E, Wigby K, Weir J, Thomson VS, Fraser L, Lazare SS, Shin YH, Grunenwald H, Lee R, Jones D, Tran D, Gross A, Daigle P, Case A, Lue M, Richardson JA, Reynders J, Defay T, Hall KP, Veeraraghavan N, Kingsmore SF. An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases. Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6.
- Background: PubMed 35676073Kingsmore SF, Cole FS. The Role of Genome Sequencing in Neonatal Intensive Care Units. Annu Rev Genomics Hum Genet. 2022 Aug 31;23:427-448. doi: 10.1146/annurev-genom-120921-103442. Epub 2022 Jun 8.
- Results publication: PubMed 33157007Dimmock DP, Clark MM, Gaughran M, Cakici JA, Caylor SA, Clarke C, Feddock M, Chowdhury S, Salz L, Cheung C, Bird LM, Hobbs C, Wigby K, Farnaes L, Bloss CS, Kingsmore SF; RCIGM Investigators. An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm. Am J Hum Genet. 2020 Nov 5;107(5):942-952. doi: 10.1016/j.ajhg.2020.10.003.
- Results publication: PubMed 33157008Cakici JA, Dimmock DP, Caylor SA, Gaughran M, Clarke C, Triplett C, Clark MM, Kingsmore SF, Bloss CS. A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants. Am J Hum Genet. 2020 Nov 5;107(5):953-962. doi: 10.1016/j.ajhg.2020.10.004.
- Results publication: PubMed 31564432Kingsmore SF, Cakici JA, Clark MM, Gaughran M, Feddock M, Batalov S, Bainbridge MN, Carroll J, Caylor SA, Clarke C, Ding Y, Ellsworth K, Farnaes L, Hildreth A, Hobbs C, James K, Kint CI, Lenberg J, Nahas S, Prince L, Reyes I, Salz L, Sanford E, Schols P, Sweeney N, Tokita M, Veeraraghavan N, Watkins K, Wigby K, Wong T, Chowdhury S, Wright MS, Dimmock D; RCIGM Investigators. A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants. Am J Hum Genet. 2019 Oct 3;105(4):719-733. doi: 10.1016/j.ajhg.2019.08.009. Epub 2019 Sep 26.
- Results publication: PubMed 37429778Cakici JA, Dimmock D, Caylor S, Gaughran M, Clarke C, Triplett C, Clark MM, Kingsmore SF, Bloss CS. Assessing Diversity in Newborn Genomic Sequencing Research Recruitment: Race/Ethnicity and Primary Spoken Language Variation in Eligibility, Enrollment, and Reasons for Declining. Clin Ther. 2023 Aug;45(8):736-744. doi: 10.1016/j.clinthera.2023.06.014. Epub 2023 Jul 8.
- Results publication: PubMed 37041447Owen MJ, Batalov S, Ellsworth KA, Wright M, Breeding S, Hugh K, Kingsmore SF, Ding Y. Rapid Whole Genome Sequencing for Diagnosis of Single Locus Genetic Diseases in Critically Ill Children. Methods Mol Biol. 2023;2621:217-239. doi: 10.1007/978-1-0716-2950-5_12.
- Derived from this study: PubMed 31196892Laurenzano SE, McFall C, Nguyen L, Savla D, Coufal NG, Wright MS, Tokita M, Dimmock D, Kingsmore SF, Newfield RS. Neonatal diabetes mellitus due to a novel variant in the INS gene. Cold Spring Harb Mol Case Stud. 2019 Aug 1;5(4):a004085. doi: 10.1101/mcs.a004085. Print 2019 Aug.
- Individual participant dataSharing planned: Yes. Samples and data may be shared confidentially with collaborators, such as commercial laboratories or technology companies. All data and sample sharing will be strictly confidential. No identifying information will be shared.
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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.
Stephen F Kingsmore, MD, DSc principal investigator
Rady Pediatric Genomics & Systems Medicine Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Genomic sequencing and molecular diagnostic results, if any. in people with Genetic Diseases and Genetic Syndrome, run by Rady Pediatric Genomics & Systems Medicine Institute 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 5 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 1 Mar 2024. 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?
Yes. Results are posted in the registry (first posted 27 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Subject's Main Provider's Perceived Clinical Utility of Genomic Sequencing (time frame: Within one week of the return of results). The study lists 3 primary outcomes in all. 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 NCT03211039, which also lists 11 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 1 Mar 2024.