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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients receiving genetic testing in the NICU; The study included 400 probands, 388 mothers, and 316 fathers who participated	Diagnostic test: rapid whole genomic sequencing (rWGS); rWGS and NewbornDx are genomic sequencing platforms; Other Names: NewbornDx

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. The Clinician Assessment of clinical utility was done collectively as a whole for both modes of genomic sequencing.	1 week
Clinical Utility of Genomic Sequencing as Assessed by Changes in Clinical Care Management or Goals of Care	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.) The intent was to examine any changes in care resulting from completing either genomic sequencing testing.	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One Year Cost-effectiveness of Entire Cohort.	Total cost of hospitalization, post-discharge follow-up until infant's 1 year CGA (corrected gestational age). Cost effectiveness of the cohort was measured across both sequence groups as a single group.	From enrollment to 1 year corrected gestational age

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Maron JL, Kingsmore S, Gelb BD, Vockley J, Wigby K, Bragg J, Stroustrup A, Poindexter B, Suhrie K, Kim JH, Diacovo T, Powell CM, Trembath A, Guidugli L, Ellsworth KA, Reed D, Kurfiss A, Breeze JL, Trinquart L, Davis JM. Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder. JAMA. 2023 Jul 11;330(2):161-169. doi: 10.1001/jama.2023.9350.
• Maron JL, Kingsmore SF, Wigby K, Chowdhury S, Dimmock D, Poindexter B, Suhrie K, Vockley J, Diacovo T, Gelb BD, Stroustrup A, Powell CM, Trembath A, Gallen M, Mullen TE, Tanpaiboon P, Reed D, Kurfiss A, Davis JM. Novel Variant Findings and Challenges Associated With the Clinical Integration of Genomic Testing: An Interim Report of the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study. JAMA Pediatr. 2021 May 1;175(5):e205906. doi: 10.1001/jamapediatrics.2020.5906. Epub 2021 May 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2022

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 6, 2025
• Last Update Submitted That Met QC Criteria: July 18, 2025
• Last Verified: July 1, 2025

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: Yes
• product manufactured in and exported from the U.S.: No