Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants

Genetic Predisposition to Disease Clinical Trial

Official title:

Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants (1U01TR003201-01A1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05161169
• Other study ID #: The BabySeq2 Project
• Status: Recruiting
• Phase: N/A
• Start date: December 21, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: August 2023
• Source: Brigham and Women's Hospital
• Contact: Bethany Zettler, MS, CGC
• Phone: (617) 264-5884
• Email: bzettler[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: July 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 0 Months to 12 Months

Eligibility

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

Related Conditions & MeSH terms

• Genetic Diseases, Inborn
• Genetic Predisposition to Disease
• Hereditary Diseases

Intervention

Genetic:
• Genome Sequencing
20 times read depth (20x) next-generation whole genome sequencing with comprehensive analysis.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Beaumont - Corewell Health East	Royal Oak	Michigan

Sponsors (13)

Lead Sponsor

Collaborator

Brigham and Women's Hospital

Baylor College of Medicine, Boston Children's Hospital, Broad Institute, Dartmouth-Hitchcock Medical Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard Pilgrim Health Care, Howard University, HudsonAlpha Institute for Biotechnology, Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, National Center for Advancing Translational Sciences (NCATS), University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MDR-associated intervention	Healthcare intervention prompted by monogenic disease risk or recessive carrier variant	1-year post-disclosure (15 months after enrollment)
Other	Suspected genetic condition	Any phenotype that develops in an infant suspected to have a genetic cause, or any genetic testing ordered as part of clinical care	1-year post-disclosure (15 months after enrollment)
Other	Cost of attributable services	Cost of healthcare services that were recommended for infants and parents as part of study disclosure session	1-year post-disclosure (15 months after enrollment)
Other	Cost of genomic services	Cost of genetic services infants and parents received after study disclosure session	1-year post-disclosure (15 months after enrollment)
Other	All healthcare costs	All health sector costs observed in medical records and survey questions regarding family out-of-pocket expenses	1-year post-disclosure (15 months after enrollment)
Primary	Monogenic disease risks (MDRs)	Pathogenic (P) and likely pathogenic (LP) variants identified relevant to infant's health (dominant or biallelic recessive disease risks)	3 months after enrollment
Primary	Carrier status variants	P and LP variants identified as recessive carrier status in infant	3 months after enrollment
Primary	MDR-associated phenotype	Signs or symptoms of monogenic disease risk identified by genome sequencing	3 months after enrollment and 1-year post-disclosure (15 months after enrollment)
Primary	Parent-Child Relationship	Parenting Stress Index, 4th Edition Short Form (scored as a percentile 0 - 100%, higher scores indicate increased stress); Vulnerable Baby Scale (scored 0 -50, higher scores indicate increased perceptions of child vulnerability)	Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
Primary	Partner Relationship	Kansas Marital Satisfaction Scale (Scored 3 to 21, higher scores indicate better marital quality; Partner Blame (novel, higher scores indicate increased blame)	Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
Primary	Personal Distress	General Anxiety Disorder-7, Patient Health Questionnaire (PHQ)-9 , Self-Blame	Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
Secondary	MDR-associated family history	Signs or symptoms of monogenic disease risk or recessive condition present in infant's biological family	3 months after enrollment and 1-year post-disclosure (15 months after enrollment)
Secondary	Feelings about genomic testing	Feelings About genomiC Testing Results (FACToR) Questionnaire	Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)