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Trial record 1 of 9029 for:    Genetic Diseases, Inborn AND genetic disorder
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Whole Genome Sequencing in the Neonatal Intensive Care Unit

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03721458
Recruitment Status : Enrolling by invitation
First Posted : October 26, 2018
Last Update Posted : May 31, 2019
Information provided by (Responsible Party):
James Broach, Milton S. Hershey Medical Center

Brief Summary:
This research is being done to see if whole genome sequencing (WGS) improves the diagnosis of patients in the NICU. Using WGS in this way, which is relatively new, researchers at Penn State College of Medicine will look at approximately 5000 genes that are known to be associated with genetic diseases to see if the neonatal patient has a known disease causing mutation. Comparing the parents' DNA with the child's will help the investigators better understand the child's DNA.

Condition or disease Intervention/treatment
Genetic Diseases, Inborn Other: Sequence

Detailed Description:

1.0 Objectives

1.1 Study Objectives The goal of this research project is to assess the potential for applying whole genome sequencing (WGS) as a diagnostic tool in the neonatal intensive care unit. Newborn children who require treatment in the neonatal intensive care unit (NICU) often suffer from genetic defects, the nature of which is difficult to diagnose. The investigators currently know of more than 5000 genes in which mutations may cause diseases that can affect newborn children, so determining which one is responsible for a new neonatal patient's disease is daunting. However, many of these diseases can be effectively treated if they are diagnosed in a timely fashion. The investigators propose to use new sequencing instrumentation coupled with rapid analytical tools to sequence NICU patients along with both parents to identify whether a patient carries a de novo mutation or compound heterozygous variants in one of the known disease genes. If so, the mutation will be confirmed in an in-house CLIA laboratory and the results provided within 72 hours to attending neonatologists to inform treatment decisions.

1.2 Primary Study Endpoints

The primary goal of this protocol will be an assessment of the degree to which WGS improves diagnosis of patients admitted to the NICU. The investigators propose to perform sequencing on approximately 50 patients over the course of this project. The investigators will evaluate on an ongoing basis the success rate for identifying clinically actionable genetic defects in the selected patients, particularly as that would inform the initial selection criteria used to enroll the patient. This information will be useful to determine whether such sequencing efforts can improve the outcome of NICU patients and which class of patients are most likely to benefit from the procedure.

1.3 Secondary Study Endpoints

A second goal will be an assessment of the effectiveness of targeted sequencing of the whole exome or a panel of 5000 genes in identifying the genetic defects revealed by whole genome sequencing and the relative cost in money and time of the various approaches. This could yield a significantly more efficient and cost effect method over that currently described elsewhere.

Finally, the investigators propose to use the data to begin to develop a cost-benefit analysis of WGS in the NICU. The investigators will assess the extent to which WGS provided a diagnosis distinct from that initially proposed by the neonatologists and the extent to which that change in diagnosis altered the treatment regimen. If the novel diagnosis did, in fact, alter treatment, The investigators would use historical data to assess the degree to which that altered treatment affected the number of days the patient remained in the NICU. The investigators can then estimate the cost savings/loss as the number of NICU days saved times the cost per day of NICU residence versus the cost of performing the sequencing over the entire cohort of sequenced patients. While this is not as rigorous as a randomized clinical trial, it would point to whether this is a methodology worth exploring in more depth.

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Whole Genome Sequencing in the Neonatal Intensive Care Unit
Actual Study Start Date : May 28, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2021

Intervention Details:
  • Other: Sequence
    Potentially identifying genetic defects that could have clinical significance

Primary Outcome Measures :
  1. Diagnosis success rate [ Time Frame: 1-2 years ]
    The investigator will determine the percent of patients for which sequencing provided a correct genetic disease diagnosis, relative to that obtained by standard clinical evaluation.

Secondary Outcome Measures :
  1. Effectiveness of exome sequencing relative to whole genome sequencing. [ Time Frame: 1-2 years ]
    The investigators will determine whether whole exome sequencing identifies all the genetic disease diagnoses identified by whole genome sequencing.

Biospecimen Retention:   Samples With DNA
Whole Blood

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patient is admitted to the NICU, evaluated by the clinical staff, recommended for participation in this study and consented.

Child:Inclusion Criteria:

  1. Age: ≤ 180 days
  2. Sex: male or female
  3. Admitted to the Hershey Medical Center NICU with a clinical presentation consistent with a genetic disease, e.g. congenital malformations, metabolic disorder, uncontrolled seizures or unexplained abnormal neurological findings.
  4. Both Biological Parents are involved in the study

Child:Exclusion Criteria:

  1. Age: > 180 days
  2. Known genetic mutation.

Biological Parents : Inclusion Criteria

  1. Age: ≥18 years
  2. Both biological parents must be willing to participate in the research.
  3. Fluent in written and spoken English.

Biological Parents: Exclusion Criteria

  1. Age: <18 years
  2. Prisoner
  3. Cognitive impairment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03721458

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United States, Pennsylvania
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
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Principal Investigator: James Broach, PhD Milton S. Hershey Medical Center

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Responsible Party: James Broach, Director of the Institute for Personalized Medicine, Milton S. Hershey Medical Center Identifier: NCT03721458     History of Changes
Other Study ID Numbers: 00007970
First Posted: October 26, 2018    Key Record Dates
Last Update Posted: May 31, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Genetic Diseases, Inborn