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

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ClinicalTrials.gov Identifier: NCT05161169
Recruitment Status : Not yet recruiting
First Posted : December 17, 2021
Last Update Posted : December 17, 2021
Sponsor:
Collaborators:
Baylor College of Medicine
Boston Children's Hospital
Broad Institute
Dartmouth-Hitchcock Medical Center
Harvard Pilgrim Health Care
Howard University
HudsonAlpha Institute for Biotechnology
Massachusetts General Hospital
Icahn School of Medicine at Mount Sinai
University of Alabama at Birmingham
National Center for Advancing Translational Science (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Robert C. Green, MD, MPH, Brigham and Women's Hospital

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.

Condition or disease Intervention/treatment Phase
Genetic Predisposition to Disease Hereditary Diseases Genetic: Genome Sequencing Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled trial (control group vs. genome sequencing intervention)
Masking: Double (Participant, Care Provider)
Primary Purpose: Screening
Official Title: Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants (1U01TR003201-01A1)
Estimated Study Start Date : February 1, 2022
Estimated Primary Completion Date : February 1, 2025
Estimated Study Completion Date : July 1, 2025

Arm Intervention/treatment
Experimental: Sequencing cohort
Infants receive genome sequencing with analysis of approximately 1000 genes associated with childhood-onset and highly actionable adult-onset disease risks. Pathogenic and likely pathogenic variants are reported to the child's parents and pediatrician. Participants also receive a detailed family history report and standard well-child care.
Genetic: Genome Sequencing
20 times read depth (20x) next-generation whole genome sequencing with comprehensive analysis.

No Intervention: Control cohort
Infants receive a detailed family history report plus standard well-child care.



Primary Outcome Measures :
  1. Monogenic disease risks (MDRs) [ Time Frame: 3 months after enrollment ]
    Pathogenic (P) and likely pathogenic (LP) variants identified relevant to infant's health (dominant or biallelic recessive disease risks)

  2. Carrier status variants [ Time Frame: 3 months after enrollment ]
    P and LP variants identified as recessive carrier status in infant

  3. MDR-associated phenotype [ Time Frame: 3 months after enrollment and 1-year post-disclosure (15 months after enrollment) ]
    Signs or symptoms of monogenic disease risk identified by genome sequencing

  4. Parent-Child Relationship [ Time Frame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) ]
    Parenting Stress Index, 4th Edition Short Form; Vulnerable Baby Scale

  5. Partner Relationship [ Time Frame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) ]
    Kansas Marital Satisfaction Scale; Partner Blame

  6. Personal Distress [ Time Frame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) ]
    General Anxiety Disorder-7, Patient Health Questionnaire (PHQ)-9 , Self-Blame


Secondary Outcome Measures :
  1. MDR-associated family history [ Time Frame: 3 months after enrollment and 1-year post-disclosure (15 months after enrollment) ]
    Signs or symptoms of monogenic disease risk or recessive condition present in infant's biological family

  2. Feelings about genomic testing [ Time Frame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) ]
    Feelings About genomiC Testing Results (FACToR) Questionnaire


Other Outcome Measures:
  1. MDR-associated intervention [ Time Frame: 1-year post-disclosure (15 months after enrollment) ]
    Healthcare intervention prompted by monogenic disease risk or recessive carrier variant

  2. Suspected genetic condition [ Time Frame: 1-year post-disclosure (15 months after enrollment) ]
    Any phenotype that develops in an infant suspected to have a genetic cause, or any genetic testing ordered as part of clinical care

  3. Cost of attributable services [ Time Frame: 1-year post-disclosure (15 months after enrollment) ]
    Cost of healthcare services that were recommended for infants and parents as part of study disclosure session

  4. Cost of genomic services [ Time Frame: 1-year post-disclosure (15 months after enrollment) ]
    Cost of genetic services infants and parents received after study disclosure session

  5. All healthcare costs [ Time Frame: 1-year post-disclosure (15 months after enrollment) ]
    All health sector costs observed in medical records and survey questions regarding family out-of-pocket expenses



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Infant participants

  • "Apparently healthy" (not suspected to have a genetic condition, and not exhibiting symptoms consistent with an infection or other transient illness)
  • Age 0-6 months (chronological or adjusted age)
  • 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 or rearing parent or guardian of an infant participating in the study ("Rearing parent" is an individual who is not biologically related to the infant, but who is dedicated to raising the child)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05161169


Contacts
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Contact: Bethany Zettler, MS, CGC (617) 264-5884 bzettler@bwh.harvard.edu
Contact: Sheyenne Walmsley, MS, GC swalmsley@bwh.harvard.edu

Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Contact: Shernine Lee       sherninelee@uabmc.edu   
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Contact: Casie Genetti, MS, CGC       casie.genetti@childrens.harvard.edu   
United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Contact: Bruce Gelb, MD       bruce.gelb@mssm.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
Baylor College of Medicine
Boston Children's Hospital
Broad Institute
Dartmouth-Hitchcock Medical Center
Harvard Pilgrim Health Care
Howard University
HudsonAlpha Institute for Biotechnology
Massachusetts General Hospital
Icahn School of Medicine at Mount Sinai
University of Alabama at Birmingham
National Center for Advancing Translational Science (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Robert C. Green, MD, MPH Brigham and Women's Hospital
Principal Investigator: Ingrid A. Holm, MD, MPH Boston Children's Hospital
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Responsible Party: Robert C. Green, MD, MPH, Professor of Medicine (Genetics), Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT05161169    
Other Study ID Numbers: The BabySeq2 Project
First Posted: December 17, 2021    Key Record Dates
Last Update Posted: December 17, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The study protocol and statistical analysis plan will be shared on clinical trials.gov
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Supporting information will be shared 6 months after study completion.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Robert C. Green, MD, MPH, Brigham and Women's Hospital:
genome sequencing
newborn screening
preventive medicine
Additional relevant MeSH terms:
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Genetic Diseases, Inborn
Disease Susceptibility
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes