Clinical trial NCT05161169: Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants
Official title: Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants (1U01TR003201-01A1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Genetic Predisposition to Disease
Hereditary Diseases
Keywords: genome sequencing
newborn screening
preventive medicine
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Baylor College of Medicine
name: Boston Children's Hospital
name: Broad Institute of MIT and Harvard
name: Dartmouth-Hitchcock Medical Center
name: Harvard Pilgrim Health Care
name: Howard University
name: HudsonAlpha Institute for Biotechnology
name: Massachusetts General Hospital
name: Icahn School of Medicine at Mount Sinai
name: University of Alabama at Birmingham
name: National Center for Advancing Translational Sciences (NCATS)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2021-12-17
Enrollment: 500
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial (control group vs. genome sequencing intervention)
Primary purpose: SCREENING

Brief summary: This research study is exploring the use of genomic sequencing in the newborn period to screen healthy babies for current and future health risks. The study will enroll a diverse cohort of 500 healthy infants and their parents from Boston, MA; New York City, NY; and Birmingham, AL. A small blood sample will be collected from each infant, and whole genome sequencing will be performed in 1/2 of the cohort following a randomized controlled trial design. 3 months later, the randomization status and sequencing results will be shared with parents and pediatricians. Investigators will study the medical, behavioral, and economic outcomes of genomic sequencing to better understand how this technology can be implemented in outpatient primary care settings.

Detailed description: The objective of this research protocol is to assess the impacts of genomic sequencing in healthy infants from ethnically and racially diverse communities as part of routine pediatric care.

Investigators will enroll a cohort of 500 healthy, ethnically and racially diverse infants from Boston, Massachusetts; New York City, New York; and Birmingham, Alabama, with planned expansion to other U.S. cities and recruitment sites. As part of this study, a stakeholder board comprised of diverse community members will provide early and regular feedback throughout the study on anticipated and ongoing community reaction to the work with sensitivity to historical injustices and cultural diversity

Primary care pediatricians from each recruitment site will be enrolled for a brief genomics education curriculum. Only infants whose healthcare providers have joined the study will be enrolled.

A small blood sample will be obtained from each enrolled infant. Participants will randomized (1:1) to receive either a family history report or a family history report plus whole genome sequencing.

Genome sequencing data will be analyzed for pathogenic and likely pathogenic variants in genes associated with childhood-onset disease risks, as well as highly actionable adult-onset disease risks. If infants have a dominant risk identified, parents may choose to be screened as part of the study.

The study team will disclose the infant's randomization status and study results during a consultation with each family, and results will be sent to the infant's pediatrician.

Parents will be surveyed at three time points over the 12 months after enrollment: baseline, immediately post-disclosure (approximately 3 months after enrollment), and 6 months post-disclosure. Surveys will assess psychosocial impacts of newborn sequencing.

Chart reviews will be performed to assess the medical outcomes and healthcare utilization costs of newborn genome sequencing.

Eligibility criteria: Inclusion Criteria:

Infant participants

* Has not previously had exome or genome sequencing
* Age 0-12 months
* Seen for well-baby pediatric care at a recruiting site
* Primary healthcare provider completed the genomics education program
* At least one parent or guardian able to participate in the study

Parent participants

* Biological parent or legal guardian of an infant participating in the study
* 18 years of age or older
* Unimpaired decision-making capacity
* English or Spanish speaking
* Available to have genetic counseling and provide consent for testing the infant

Exclusion Criteria:

* Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
* Any infant in which clinical considerations preclude collecting blood via heel stick

Primary outcomes:
measure: Monogenic disease risks (MDRs)
timeFrame: 3 months after enrollment
measure: Carrier status variants
timeFrame: 3 months after enrollment
measure: MDR-associated phenotype
timeFrame: 3 months after enrollment and 1-year post-disclosure (15 months after enrollment)
measure: Parenting stress, relationship dysfunction
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
measure: Relationship satisfaction
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
measure: General anxiety
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
Secondary outcomes:
measure: MDR-associated family history
timeFrame: 3 months after enrollment and 1-year post-disclosure (15 months after enrollment)
measure: Intervention prompted by genetic or family history report
timeFrame: 6 months post-disclosure (9 months after enrollment)
measure: Suspected genetic condition
timeFrame: 6 months post-disclosure (9 months after enrollment)
measure: Child vulnerability
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
measure: Feelings about genomic testing
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
measure: Partner blame
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
measure: General depression
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
measure: Self blame
timeFrame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
Other outcomes:
measure: Cost of attributable services
timeFrame: 6 months post-disclosure (9 months after enrollment)
measure: Cost of genomic services
timeFrame: 6 months post-disclosure (9 months after enrollment)
measure: All healthcare costs
timeFrame: 6 months post-disclosure (9 months after enrollment)
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont - Corewell Health East
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Brigham and Women's Hospital
name: Robert C. Green, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Ingrid A. Holm, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: