Genomic Predictors of Recurrent Pregnancy Loss

Recurrent Pregnancy Loss Clinical Trial

— GPRPL  

Official title:

Large Scale Genome Sequencing and Integrative Analyses to Define Genomic Predictors of Recurrent Pregnancy Loss

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05444283
• Other study ID #: 2000029802
• Secondary ID: 1R01HD105267-01
• Status: Recruiting
• Start date: September 1, 2021
• Est. completion date: September 2026

Study information

• Verified date: August 2023
• Source: Yale University
• Contact: Yong-Hui Jiang, MD, PhD
• Phone: 2037852429
• Email: yong-hui.jiang[@]yale.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The overall goals of this proposal are to determine the genetic architecture of recurrent pregnancy loss (RPL) and to discover genomic predictors of RPL.

Description:

The following specific aims are proposed: Aim 1: Collect clinically well-characterized samples from trios (product of conception (POC), biological mother, and biological father) with unexplained RPL. Specifically, a cohort of 1,000 trios that are rigorously-phenotyped will be recruited, and for which couples' RPL is not attributable to known causes. The POC and parental DNA samples will be collected. If it is necessary for the purpose of determining the pathogenicity of sequence variants from the trio, collecting DNA samples from other family members after consent will also be considered. The study team may also request DNA or POC tissues from a prior pregnancy loss(es) if available. Aim 2: A whole genome sequencing (WGS) at the Yale Center for Genome Analysis (YCGA) will be performed and bioinformatic analyses to identify pathogenic variants in included trios will performed as well. Pathogenic variants will be comprehensively defined and fully annotated variant maps in all included trios to provide the substrate for subsequent novel gene discovery, and ultimately, the development of clinical diagnostic tests will be generated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: September 2026
• Est. primary completion date: September 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

1. Women with loss of a current singleton pregnancy at < 20 0/7 weeks gestation (documented by ultrasonography or histopathological examination) and one or more prior pregnancy losses.

2. Euploid current pregnancy by karyotype or microarray (a limited number of aneuploid losses will be included as part of the pilot)

3. No history of parental karyotype abnormalities

4. No history of antiphospholipid antibody syndrome

5. No evidence of uncontrolled diabetes

6. No evidence of uncontrolled thyroid disease

7. No history of autoimmune disease (SLE, RA)

8. No history of uterine anomalies

9. No history of cervical insufficiency

Related Conditions & MeSH terms

• Abortion, Habitual
• Abortion, Spontaneous
• Fetal Death
• Recurrence
• Recurrent Pregnancy Loss

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	University of Texas at Austin	Austin	Texas
United States	Gaelle Massoud	Baltimore	Maryland
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Wayne State University	Detroit	Michigan
United States	Pennsylvania State University	Hershey	Pennsylvania
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Texas at San Antonio	San Antonio	Texas

Sponsors (12)

Lead Sponsor	Collaborator
Yale University	Columbia University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Johns Hopkins University, Northwestern University, Penn State University, The University of Texas Health Science Center at San Antonio, University of Chicago, University of Colorado, Denver, University of Oklahoma, University of Texas at Austin, Wayne State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine genetic etiology for Recurrent Pregnancy Loss	The WGS tool will be used to analyze the POC sample and parental blood samples to determine the clinical reportable genetic cause for RPL	5 years