Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants (1U01TR003201-01A1)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 500
- 试验地点
- 4
- 主要终点
- MDR-associated phenotype
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 0 Months 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Genome Sequencing (Genetic)
Control cohort
Infants receive a detailed family history report plus standard well-child care.
结局指标
主要结局
MDR-associated phenotype
时间窗: 3 months after enrollment and 1-year post-disclosure (15 months after enrollment)
Signs or symptoms of monogenic disease risk identified by genome sequencing
Relationship satisfaction
时间窗: 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)
General anxiety
时间窗: Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)
General Anxiety Disorder-7
Monogenic disease risks (MDRs)
时间窗: 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
时间窗: 3 months after enrollment
P and LP variants identified as recessive carrier status in infant
Parenting stress, relationship dysfunction
时间窗: 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)
次要结局
- MDR-associated family history(3 months after enrollment and 1-year post-disclosure (15 months after enrollment))
- Intervention prompted by genetic or family history report(6 months post-disclosure (9 months after enrollment))
- Suspected genetic condition(6 months post-disclosure (9 months after enrollment))
- General depression(Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment))
- Partner blame(Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment))
- Child vulnerability(Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment))
- Feelings about genomic testing(Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment))
- Self blame(Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment))
研究者
Robert C. Green, MD, MPH
Professor of Medicine (Genetics)
Brigham and Women's Hospital