Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants
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|ClinicalTrials.gov Identifier: NCT05161169|
Recruitment Status : Recruiting
First Posted : December 17, 2021
Last Update Posted : May 26, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Genetic Predisposition to Disease Hereditary Diseases||Genetic: Genome Sequencing||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized controlled trial (control group vs. genome sequencing intervention)|
|Masking:||Double (Participant, Care Provider)|
|Official Title:||Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants (1U01TR003201-01A1)|
|Actual Study Start Date :||December 21, 2022|
|Estimated Primary Completion Date :||February 1, 2025|
|Estimated Study Completion Date :||July 1, 2025|
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.
- 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)
- Carrier status variants [ Time Frame: 3 months after enrollment ]P and LP variants identified as recessive carrier status in infant
- 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
- 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 (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)
- Partner Relationship [ Time Frame: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) ]Kansas Marital Satisfaction Scale (Scored 3 to 21, higher scores indicate better marital quality; Partner Blame (novel, higher scores indicate increased blame)
- 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
- 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
- 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
- MDR-associated intervention [ Time Frame: 1-year post-disclosure (15 months after enrollment) ]Healthcare intervention prompted by monogenic disease risk or recessive carrier variant
- 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
- 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
- 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
- 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
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.
|Ages Eligible for Study:||0 Months to 12 Months (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- "Apparently healthy" (not suspected to have a genetic condition, and not exhibiting symptoms consistent with an infection or other transient illness)
- 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
- 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
- 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
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
|Contact: Bethany Zettler, MS, CGC||(617) firstname.lastname@example.org|
|Contact: Sheyenne Walmsley, MS, GCemail@example.com|
|United States, Alabama|
|University of Alabama at Birmingham||Not yet recruiting|
|Birmingham, Alabama, United States, 35294|
|Contact: Shernine Lee firstname.lastname@example.org|
|United States, Massachusetts|
|Boston Children's Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Bethany Zettler, MS, CGC email@example.com|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Not yet recruiting|
|New York, New York, United States, 10029|
|Contact: Bruce Gelb, MD firstname.lastname@example.org|
|Principal Investigator:||Robert C. Green, MD, MPH||Brigham and Women's Hospital|
|Principal Investigator:||Ingrid A. Holm, MD, MPH||Boston Children's Hospital|
|Responsible Party:||Robert C. Green, MD, MPH, Professor of Medicine (Genetics), Brigham and Women's Hospital|
|Other Study ID Numbers:||
The BabySeq2 Project
|First Posted:||December 17, 2021 Key Record Dates|
|Last Update Posted:||May 26, 2023|
|Last Verified:||May 2023|
|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|
Statistical Analysis Plan (SAP)
|Time Frame:||Supporting information will be shared 6 months after study completion.|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Genetic Diseases, Inborn
Genetic Predisposition to Disease