Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Hydrops: Diagnosing & Redefining Outcomes With Precision Study (HyDROPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03412760
Recruitment Status : Recruiting
First Posted : January 26, 2018
Last Update Posted : May 8, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Fetal Health Foundation
Information provided by (Responsible Party):
Teresa Sparks, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE January 10, 2018
First Posted Date  ICMJE January 26, 2018
Last Update Posted Date May 8, 2019
Actual Study Start Date  ICMJE October 11, 2018
Estimated Primary Completion Date November 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2018)
Genetic variants detected on whole exome sequencing that implicate a cause of non-immune hydrops fetalis (NIHF) and other birth defects. [ Time Frame: Turn around time for whole exome sequencing results is 2-4 weeks. ]
Both NIHF and birth defects can be caused by a variety of genetic variants that researchers are continuing to learn more about. Whole exome sequencing will yield information about the specific genetic variants present in cases of NIHF and other birth defects, and about the specific diseases implicated by these variants. Investigators will determine the proportion of cases seen in the setting of particular genetic variants, and will correlate phenotypic outcomes with specific genotypes.
Original Primary Outcome Measures  ICMJE
 (submitted: January 20, 2018)
Genetic mutations detected on whole exome sequencing that explain the cause of non-immune hydrops fetalis (NIHF) and other birth defects. [ Time Frame: Turn around time for whole exome sequencing results is 2-4 weeks ]
Both NIHF and birth defects can be caused by a variety of genetic mutations that researchers are continuing to learn more about. Whole exome sequencing will yield information about the specific genetic mutations present in cases of NIHF and other birth defects, and about the specific diseases caused by these mutations. Investigators will determine the proportion of cases caused by particular genetic mutations, and will correlate phenotypic outcomes with specific genotypes.
Change History Complete list of historical versions of study NCT03412760 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydrops: Diagnosing & Redefining Outcomes With Precision Study
Official Title  ICMJE Hydrops: Diagnosing & Redefining Outcomes With Precision Study
Brief Summary This is a multi-center, prospective study designed to investigate the genetic etiologies of non-immune hydrops fetalis (NIHF) and other birth defects. In the setting of NIHF, up to 46% of prenatally diagnosed cases remain of unknown etiology after standard work up, and a substantial proportion of other birth defects remain of unknown etiology as well. The investigators are performing whole exome sequencing (WES) for the fetus or neonate, as well as both biological parents, in each of these cases to investigate the underlying genetic etiology.
Detailed Description

Between 1:1700 and 1:3000 pregnancies are affected by non-immune hydrops fetalis (NIHF), and this condition is associated with significant perinatal risks, ranging from preterm birth to Ballantyne (maternal mirror) syndrome, stillbirth, and neonatal death. Birth defects affect 1:33 pregnancies, and are the leading cause of infant death (contributing to approximately 20% of infant deaths). The investigators are performing whole exome sequencing (WES) for the fetus or neonate, as well as both biological parents, in each of these cases to investigate the underlying genetic etiology.

This study is open for enrollment. Established collaborating sites include all five sites of the University of California Fetal-Maternal Consortium (UCfC). The UCfC is a collaborative network of investigators with representatives from five UC medical centers (UC Davis, UC Irvine, UC Los Angeles, UC San Diego, UC San Francisco). In addition to recruiting through these five centers, the investigators are also recruiting nationally in order to develop a diverse cohort of NIHF cases and other birth defects.

In addition to performing trio whole exome sequencing (WES), the investigators are collecting clinical data prospectively on all cases of NIHF and other birth defects, including demographics, medical and obstetric history, prenatal and delivery course, and postnatal outcomes until the infant is discharged from the hospital.

The specific research aims include:

  1. Create a multi-center registry to collect clinical data for cases of non-immune hydrops fetalis (NIHF) and other birth defects.
  2. Investigate the genetic variants underlying NIHF and other birth defects via whole exome sequencing (WES).
  3. Develop a precision-based approach to antenatal and neonatal care in cases of NIHF and other birth defects.

This research will contribute novel information about the frequency and types of genetic disorders in fetuses and newborns with a diagnosis of NIHF and other birth defects, enabling providers to more accurately counsel about prognosis and individualize perinatal care. This information will also facilitate informed decision-making for parents, allow the care team to anticipate specific perinatal needs, and enable more precise counseling for the parents about recurrence risks for NIHF and other birth defects. Further, examining genotype-phenotype correlations will facilitate a precision-based approach to again individualize counseling and also enable targeted neonatal (and in the future, antenatal) therapies such as enzyme replacement and stem cell transplantation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
All cases of non-immune hydrops fetalis (NIHF) or other birth defects enrolled in the study will be offered whole exome sequencing (WES). This will be trio WES ideally, meaning that WES will be offered for the affected fetus as well as for both of the biologic parents. If one or both of the parents are unavailable, then duo or proband-only WES could be done, respectively.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Hydrops Fetalis
  • Birth Defect
  • Fetal Anomaly
Intervention  ICMJE Diagnostic Test: Trio whole exome sequencing
Expansive genetic test performed for affected fetus as well as for both biological parents where possible (or for only one parent where applicable).
Study Arms  ICMJE Experimental: Trio whole exome sequencing
There is only one arm of this study. All enrolled participants will be offered trio whole exome sequencing (or duo where necessary). Please refer to the Study Design section for further details.
Intervention: Diagnostic Test: Trio whole exome sequencing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 20, 2018)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date November 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Singletons or dichorionic twin pregnancies that are diagnosed prenatally with non-immune hydrops fetalis (NIHF) or another birth defect. Cases with chromosomal abnormalities, postnatal samples, and stillbirths will still be included.

Exclusion Criteria:

  • Monochorionic twin pregnancies and cases of hydrops fetalis that are attributed to red cell alloimmunization (due to hydrops fetalis caused by different pathophysiologic processes).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Teresa Sparks, MD 415-514-9399 hydrops@ucsf.edu
Contact: Dougherty Val, MS 415-514-0730 dougherv@ucsf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03412760
Other Study ID Numbers  ICMJE HydropsUCSF
5K12HD001262 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: De-identified data will be shared only in accordance with NIH/NICHD regulations as the Women's Reproductive Health Research (WRHR) grant is a funding source for this study, and is co-sponsored by these bodies.
Responsible Party Teresa Sparks, University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Fetal Health Foundation
Investigators  ICMJE
Principal Investigator: Teresa Sparks, MD University of California, San Francisco
Principal Investigator: Mary Norton, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP