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Genomic Sequencing for Childhood Risk and Newborn Illness

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ClinicalTrials.gov Identifier: NCT02422511
Recruitment Status : Recruiting
First Posted : April 21, 2015
Last Update Posted : March 1, 2018
Sponsor:
Collaborators:
Boston Children’s Hospital
Baylor College of Medicine
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:

The Genomic Sequencing for Childhood Risk and Newborn Illness (the BabySeq Project) is a research study exploring the use of genomic sequencing in newborns. The National Institutes of Health is funding this study.

The investigators will enroll 240 healthy infants and their parents from the Brigham and Women's Hospital (BWH) Well Newborn Nursery and 240 sick infants and their parents at Boston Children's Hospital (BCH) or the BWH Neonatal Intensive Care Unit (NICU). A small blood sample will be collected from each infant and genome sequencing may be performed. Six weeks later, results are returned and explained. Over 12 months the investigators are studying the experiences of parents and pediatricians of infants who receive sequencing to help understand how best to use genomics in pediatric care.


Condition or disease Intervention/treatment Phase
Hereditary Disease Genetic Predisposition to Disease Genetic: Genomic sequencing Other: Family history report Not Applicable

Detailed Description:

The objective of this research protocol is to conduct a randomized clinical trial to assess the benefits and risks of adding the information from a genomic sequencing report to physician-mediated medical care of newborns during their pediatric years.

The investigators will enroll 240 healthy infants and their parents from the Brigham and Women's Hospital (BWH) Well Newborn Nursery and 240 sick infants and their parents at Boston Children's Hospital (BCH) or the BWH Neonatal Intensive Care Unit (NICU).

A small blood sample will be obtained from each enrolled infant. Samples will be collected from all infants enrolled, regardless of the arm to which they are assigned, in order to follow the same protocol for all subjects prior to randomization.

Infants within each cohort will be randomized (1:1) to either standard-of-care (family history and standard newborn screening report) or to standard-of-care plus genomic sequencing.

A study physician and genetic counselor will disclose the infant's randomization assignment and study results during an in-person consultation with each family. The study physician and genetic counselor will provide the consultation to families utilizing all available medical information. In the sequencing arm of the study, this will include the medical history, physical exam, family history, standard newborn screening (NBS) report and sequencing report(s). In the non-sequencing arm of the study, this will include the medical history, physical exam, family history and standard NBS report.

Parents will be surveyed at four points over the 12 months after enrollment: baseline, immediately post-disclosure (approximately 6 weeks after enrollment), 3 months post-disclosure, and at 10 months post-disclosure.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Genomic Sequencing for Childhood Risk and Newborn Illness (The BabySeq Project)
Study Start Date : May 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Arm Intervention/treatment
Well Infant Cohort, No Sequencing
Healthy infants and their parents enrolled through the Brigham and Women's Hospital (BWH) Well Newborn Nursery who are randomized not to receive sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, and any potentially medically relevant findings from the baby's medical history/physical exam.
Other: Family history report
Participants from all arms of the study will have a family history taken by a study genetic counselor. Information collected through the family history will be summarized in a family history report that will be reviewed with all participants.

Well Infant Cohort, Sequencing
Healthy infants and their parents enrolled through Brigham and Women's Hospital (BWH) Well Newborn Nursery who are randomized to receive genomic sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, any potentially medically relevant findings from the baby's medical history/physical exam, and the results of the genomic sequencing report.
Genetic: Genomic sequencing
Both sick and healthy infants randomized to receive genomic sequencing will receive a 'Genomic Newborn Sequencing Report' (GNSR) which will include pathogenic or likely pathogenic variants identified in genes associated with childhood-onset disease.

Other: Family history report
Participants from all arms of the study will have a family history taken by a study genetic counselor. Information collected through the family history will be summarized in a family history report that will be reviewed with all participants.

Sick Infant Cohort, No Sequencing
Infants and their parents enrolled through Boston Children's Hospital (BCH) and the BWH Neonatal Intensive Care Unit who are randomized not to receive sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, and any potentially medically relevant findings from the baby's medical history/physical exam.
Other: Family history report
Participants from all arms of the study will have a family history taken by a study genetic counselor. Information collected through the family history will be summarized in a family history report that will be reviewed with all participants.

Sick Infant Cohort, Sequencing
Infants and their parents enrolled through Boston Children's Hospital and the BWH Neonatal Intensive Care Unit who are randomized to receive genomic sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, any potentially medically relevant findings from the baby's medical history/physical exam, and the results of the genomic sequencing report.
Genetic: Genomic sequencing
Both sick and healthy infants randomized to receive genomic sequencing will receive a 'Genomic Newborn Sequencing Report' (GNSR) which will include pathogenic or likely pathogenic variants identified in genes associated with childhood-onset disease.

Other: Family history report
Participants from all arms of the study will have a family history taken by a study genetic counselor. Information collected through the family history will be summarized in a family history report that will be reviewed with all participants.




Primary Outcome Measures :
  1. Change in family/physician healthcare utilization immediately after results disclosure compared to 3 and 10 months post-disclosure [ Time Frame: Immediately post-disclosure (parents-approximately 6 weeks after enrollment), Post-disclosure (physician surveys administered approximatley 4 weeks after results disclosure), 3 months post-disclosure (parents), 10 months post-dislcosure (parents) ]
    Assessed in physician and parent surveys

  2. Change in baseline family relationship and personal distress levels compared to immediately post-disclosure, 3 months post-disclosure and 10 months post-disclosure [ Time Frame: Baseline, immediately post-disclosure (approximately 6 weeks after enrollment), 3 months post-disclosure, 10 months post-disclosure ]
    Assessed in parent surveys via questions assessing: parent-child bonding, personal distress, perceptions of child, partner relationship, child-centered stress


Secondary Outcome Measures :
  1. Participant characteristics [ Time Frame: Baseline ]
    Assessed in parent and physician surveys via questions assessing: sociodemographics, personal and family history, genetic literacy and numeracy, dispositions

  2. Change in baseline perceived utility of genomic results compared to post-disclosure [ Time Frame: Baseline, 3 months post-disclosure (parents), post-disclosure (physicians - 4 weeks after results disclosure), end of study (physicians - up to 40 months after completion of the baseline survey) ]
    Assessed in parent and physician surveys via questions assessing: expectations, satisfaction with and perceived utility of genomic results


Other Outcome Measures:
  1. Change in baseline physician confidence and attitudes about genome sequencing compared to end of study (up to 40 months later) [ Time Frame: Baseline, end of study (up to 40 months after completion of the baseline survey) ]
    Assessed in physician surveys

  2. Parent understanding and recall of study results [ Time Frame: 3 months post-disclosure ]
    Assessed in parent surveys via questions assessing: results recall, subjective understanding, importance of understanding



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Newborns and Parents at Brigham and Women's Hospital (BWH) Well Newborn Nursery:

Inclusion Criteria :

  1. Infants born at BWH and admitted to the Well Newborn Nursery
  2. At least one biological parent is physically available to have genetic counseling, donate DNA, and provide consent for testing the infant. If the second biological parent is known but not physically present, the second biological parent must be available to have genetic counseling by phone, return a signed consent form by mail, and donate DNA via a mailed saliva kit. If there is a "rearing parent" (an individual who is not biologically related to the infant, but who is dedicated to raising the child), that individual must also provide consent but will not be asked to submit a saliva sample.
  3. Mother (either rearing or biological) carried the pregnancy

Exclusion Criteria:

  1. Parents are non-English speaking
  2. Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
  3. Mother or father younger than 18 years of age
  4. Mother or father with impaired decisional capacity
  5. Age of infant is older than 30 days
  6. One of a multiple gestation
  7. Any infant in which clinical considerations preclude drawing 1.0 ml of blood
  8. Missing consent of either biological parent (if known) or rearing parent (if applicable)

Sick Newborns and Parents at Boston Children's Hospital (BCH) or the BWH NICU:

Inclusion Criteria:

  1. Infants admitted to BCH or the BWH NICU
  2. At least one biological parent is physically available to have genetic counseling, donate DNA, and provide consent for testing the infant. If the second biological parent is known but not physically present, the second biological parent must be available to have genetic counseling by phone, return a signed consent form by mail, and donate DNA via a mailed saliva kit. If there is a "rearing parent" (an individual who is not biologically related to the infant, but who is dedicated to raising the child), that individual must also provide consent but will not be asked to submit a saliva sample.
  3. Mother (either biological or rearing) carried the pregnancy

Exclusion Criteria:

  1. Parents are non-English speaking
  2. Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
  3. Mother or father younger than 18 years of age
  4. Mother or father with impaired decisional capacity
  5. Age of infant is older than 30 days
  6. One of a multiple gestation
  7. Any infant in which clinical considerations preclude drawing 1.0 ml of blood
  8. Hospital admission expected to be less than 72 hours
  9. Missing consent of either biological parent (if known) or rearing parent (if applicable)
  10. Previously performed exome/genome sequencing on patient

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): NCT02422511


Contacts
Contact: Shawn M. Fayer, MSc, MS 617-264-5884 sfayer1@bwh.harvard.edu
Contact: Meghan Towne, MS, CGC 617-919-4287 Meghan.Towne@childrens.harvard.edu

Locations
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Meghan Towne, MS, CGC    617-919-4287    Meghan.Towne@childrens.harvard.edu   
Principal Investigator: Alan H. Beggs, PhD         
Sub-Investigator: Ingrid Holms, MD, MPH         
Sub-Investigator: Pankaj Agrawal, MD, MMSc         
Sub-Investigator: Peter Park, PhD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Shawn M Fayer, MSc, MS    617-264-5884    sfayer1@bwh.harvard.edu   
Principal Investigator: Robert C. Green, MD, MPH         
Sub-Investigator: Richard Parad, MD, MPH         
Sub-Investigator: Heidi Rehm, PhD         
Sub-Investigator: Ozge Birsoy, PhD         
Sub-Investigator: Joel Krier, MD, MMSc         
Sponsors and Collaborators
Brigham and Women's Hospital
Boston Children’s Hospital
Baylor College of Medicine
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Robert C. Green, MD, MPH Brigham and Women's Hospital
Principal Investigator: Alan Beggs, PhD Boston Children’s Hospital

Publications:
Green RC, Rehm HL, Kohane IS. Clinical genome sequencing. In: Ginsburg GS, Willard HF, eds. Genomic and Personalized Medicine. Vol 1. 2nd ed. San Diego: Academic Press; 2013: 102-122.
The President's Council on Bioethics. The changing moral focus of newborn screening: An ethical analysis by the President's Council on Bioethics. 2008; http://bioethics.georgetown.edu/pcbe/reports/newborn_screening.
Connolly M, Holm I, Beggs A, Agrawal P. Bringing current research technology to the clinic: The Manton Center for Orphan Disease Research Gene Discovery Core (Platform Abstract/Program 45). Paper presented at: 12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics; October 12, 2011, 2011; Montreal, Canada.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert C. Green, MD, MPH, Associate Professor of Medicine, Division of Genetics, Department of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT02422511     History of Changes
Other Study ID Numbers: The BabySeq Project
U19HD077671 ( U.S. NIH Grant/Contract )
First Posted: April 21, 2015    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018

Keywords provided by Robert C. Green, MD, MPH, Brigham and Women's Hospital:
Genome Sequencing
Exome Sequencing
Newborn Screening
Childhood Onset Genetic Conditions

Additional relevant MeSH terms:
Disease Susceptibility
Genetic Predisposition to Disease
Genetic Diseases, Inborn
Disease Attributes
Pathologic Processes