Genomic Medicine for Ill Neonates and Infants (The GEMINI Study) (GEMINI)

The Genomic Medicine for Ill Neonates and Infants (The GEMINI Study) is a research study aimed at comparing the clinical and economic utility of performing rapid whole genomic sequencing versus a targeted genomic sequencing panel on neonates and infants suspected of having a genetic disorder. This study is funded by the National Institutes of Health.

This multicenter, prospective clinical trial will enroll 400 subjects at the Floating Hospital for Children at Tufts Medical Center (Boston, MA), Cincinnati Children's Hospital Medical Center (Cincinnati, OH), Mount Sinai Kravis Children's Hospital (New York, NY), North Carolina Children's Hospital (Chapel Hill, NC), Children's Hospital of Pittsburgh (Pittsburgh, PA), and Rady Children's Hospital (San Diego, CA).

Study Overview

• Status: Completed
• Conditions: Pediatric: Genetic Syndrome
• Intervention / Treatment: Diagnostic test: rapid whole genomic sequencing (rWGS)

Detailed Description

This multicenter, prospective clinical trial will examine the diagnostic yield and clinical utility of NewbornDx, a targeted genomic sequencing panel for use in the neonate, and rapid whole genomic sequencing (rWGS) testing in high-risk infants with signs/symptoms consistent with a possible genetic disorder. Infants will undergo NewbornDx and rWGS (proband) testing. The biological parent(s), when available, will undergo NewbornDx testing at the same time as the infant. For rWGS,the infant will undergo testing first. If a specific diagnosis that is consistent with the phenotype is not made with rWGS proband analysis alone, the parent(s) will undergo rWGS. The study will also evaluate the cost effectiveness of each test as well as standard of care (SOC) testing. A retrospective chart review of infants with suspected genetic disorders will be done to understand 1-year cost and health outcomes that would have been incurred in the absence of the advanced testing. The resulting data from the trial will be used in the economic evaluation comparing NewbornDx, rWGS, and SOC over a 1-year period and used as basis to simulate the lifetime cost-effectiveness of these testing strategies. A web-based clinical reference database to provide references, clinical management guidelines, opportunities for clinical trial participation, and support groups for each condition will be developed with separate interfaces for the parent/guardian(s) and medical provider. The clinical reference database will be qualitatively assessed by a survey of medical providers.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented informed consent from the parent/guardian
• Signs/symptoms consistent with a possible genetic disorder
• Admitted to a hospital participating in this study at the time of enrollment
• Less than one year corrected gestational age

Exclusion Criteria:

• A known genetic diagnosis (e.g. prenatal testing)
• Major congenital anomaly associated with a chromosomal anomaly detected on prenatal testing
• Presence of documented congenital infection
• Infants considered non-viable due to prematurity (< 23 0/7 weeks GA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of subjects with a confirmed genetic disorder detected by NewbornDx	If NewbornDx diagnoses a genetic disorder	1-2 weeks
The number of subjects with a confirmed genetic disorder detected by rWGS	If rWGS diagnoses a genetic disorder	1-2 weeks
Time in hours to a positive result by NewbornDx	Duration of time (hours) to determine diagnosis by NewbornDx	1-2 weeks
Time in hours to a positive result by rWGS	Duration of time (hours) to determine diagnosis by rWGS	1-2 weeks
Perception of the clinical utility of genomic sequencing	The Clinician Assessment of Clinical Utility assessed by physician survey using units on a likert scale with 1 meaning not useful at all and 5 meaning very useful	1 week
Clinical utility of genomic sequencing as assessed by changes in clinical care management	The Clinician Assessment of Clinical Utility assessed by physician survey selecting the specific types of 35 possible management changes (i.e. surgical intervention implemented, medication changed, etc.)	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One year cost-effectiveness of standard of care (SOC), NewbornDx and rWGS testing	All three care platforms will be assessed for their cost-effectiveness based on Quality-Adjusted-Life Year. Qualities are assessed on a scale ranging from 0 (deceased) to 1 (perfect health).	5 years
Lifetime cost-effectiveness of SOC, NewbornDx and rWGS testing	All three care platforms will be assessed for their cost-effectiveness based on Quality-Adjusted-Life Year. Qualities are assessed on a scale ranging from 0 (deceased) to 1 (perfect health).	5 years
User satisfaction with the clinical reference database providing physician-specific information about treatments, resources and ongoing clinical trials regarding the genetic disorder diagnosed: likert scale	The Clinician Satisfaction with Return of Genomic Testing Information survey assessed by physicians using units on a likert scale with 1 meaning not useful at all and 5 meaning very useful	5 years

Collaborators and Investigators

• Sponsor: Tufts Medical Center
• Collaborators: University of Pittsburgh; Children's Hospital Medical Center, Cincinnati; MOUNT SINAI HOSPITAL; Rady Children's Hospital, San Diego; North Carolina Children's Hospital
• Investigators: Principal Investigator: Jill L Maron, MD, MPH, Women and Infants Hospital of Rhode Island; Principal Investigator: Jonathan M Davis, MD, Tufts Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: JHUSIRB00000007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sequencing data that relates genomic data to phenotype or other biological states will be generated and released in accordance to the NIH GDS Policy. Data, including genome sequences (fastq files), variants (vcf files), and associated HIPAA compliant clinical metadata will be deposited in the Longitudinal Pediatric Data Resource (LPDR; https://www.nbstrn.org/research-tools/longitudinal-pediatric-data-resource). The LPDR, in turn, will deposit data in the NCBI dbGAP. Variants with ACMG recommended pathogenicity assessments will be deposited in ClinVar. Novel disorder gene assertions will be deposited in ClinGen (https://clinicalgenome.org/).
• IPD Sharing Time Frame: Annual data submissions supplemented by specific dataset deposits as manuscripts arising from this work are submitted for publication.
• IPD Sharing Access Criteria: Individual level data will be made available through controlled access. Genomic Summary Results will be made available through unrestricted access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No