Clinical trial NCT03890679: Genomic Medicine for Ill Neonates and Infants (The GEMINI Study)
Official title: Genomic Medicine for Ill Neonates and Infants (The GEMINI Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pediatric: Genetic Syndrome
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: Rady Children's Hospital, San Diego
name: Children's Hospital Medical Center, Cincinnati
name: MOUNT SINAI HOSPITAL
name: North Carolina Children's Hospital
name: University of Pittsburgh
First posted: 2019-03-26
Enrollment: 400
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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).

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.

Eligibility criteria: 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)

Primary outcomes:
measure: The number of subjects with a confirmed genetic disorder detected by NewbornDx
timeFrame: 1-2 weeks
measure: The number of subjects with a confirmed genetic disorder detected by rWGS
timeFrame: 1-2 weeks
measure: Time in hours to a positive result by NewbornDx
timeFrame: 1-2 weeks
measure: Time in hours to a positive result by rWGS
timeFrame: 1-2 weeks
measure: Perception of the clinical utility of genomic sequencing
timeFrame: 1 week
measure: Clinical utility of genomic sequencing as assessed by changes in clinical care management
timeFrame: 1 week
Secondary outcomes:
measure: One year cost-effectiveness of standard of care (SOC), NewbornDx and rWGS testing
timeFrame: 5 years
measure: Lifetime cost-effectiveness of SOC, NewbornDx and rWGS testing
timeFrame: 5 years
measure: 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
timeFrame: 5 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Women and Infants Hospital of Rhode Island
name: Jill L Maron, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Jonathan M Davis, MD
role: PRINCIPAL_INVESTIGATOR
References: