A New Prenatal Blood Test for Down Syndrome

Down Syndrome Clinical Trial

— RNA  

Official title:

The RNA (RNA-Based Noninvasive Aneuploidy) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877292
• Other study ID #: 09-0004
• Status: Completed
• Phase: N/A
• First received: April 6, 2009
• Last updated: June 1, 2015
• Start date: February 2009
• Est. completion date: May 2011

Study information

• Verified date: June 2015
• Source: Women and Infants Hospital of Rhode Island
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The study will examine the sensitivity and specificity of a circulating cell-free nucleic acid test (DNA/RNA) to identify Down syndrome between about 10 weeks and 21 weeks 6 days gestation. In addition, the new test may be used to identify trisomy 13 and 18 as part of a more complete laboratory developed test. We hypothesize that the new circulating cell-free fetal NA-based test will accurately and precisely measure specific fetal markers in maternal circulation and that measurement will lead to the ability to noninvasively identify with high sensitivity and specificity, fetal chromosome abnormalities, such as Down syndrome.

Description:

The RNA study is an observational trial whose primary aim is to document the performance (sensitivity and specificity) of one or more laboratory developed test (LDT) using circulating cell-free fetal nucleic acids from maternal plasma to identify Down syndrome. Multiple test modalities are being pursued, including massively parallel sequencing and those utilizing differential methylation. The population being studied is women already having a diagnostic test (e.g., amniocentesis, CVS) between 10 weeks and 21 weeks 6 days gestation, and whose pregnancy is at high risk for having Down syndrome. The women provide informed consent. The karyotype will provide the gold standard against which the LDT test is judged. Samples and karyotypes will be collected from up to 25 prenatal diagnostic centers around the world and tested in several laboratories in the United States. The secondary aim is to develop a nucleic acid sample bank to allow documentation of subsequent improvements or new methodologies to identify fetal aneuploidy using circulating cell-free fetal nucleic acids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4664
• Est. completion date: May 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnant women between about 10 weeks and 21 weeks 6 days gestation who are undergoing a diagnostic procedure (i.e., chorionic villus sampling or amniocentesis) for karyotype analysis who have, on average, a high prevalence of Down syndrome (about 1:30 to 1:50).

• Three main sources are pregnancies screen positive for:

1. the combined test at 10 to 13 weeks (NT, PAPP-A and hCG)

2. the second trimester quadruple test at 15 to 18 weeks gestation

3. integrated screening (PAPP-A and the quadruple test, with or without NT).

• Variations of the integrated test such as sequential testing will also be acceptable.

• Other, less common high risk groups would be women having diagnostic testing because of maternal age of 38 years or older at delivery, pregnancies with an abnormal ultrasound highly suggestive of a chromosome abnormality (e.g., major heart defect, clenched fist), and women with an inherited form of Down syndrome (Robertsonian translocation).

Exclusion Criteria:

• Nonpregnant women and women at relatively low risk for a Down syndrome baby.

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Down Syndrome
• Trisomy 21

Locations

Country	Name	City	State
Argentina	Center for Medical Education and Clinical Investiagtion	Buenos Aires
Argentina	Sociedad Italiana de Beneficencia en Buenos Aires - Hospital Italiano	Buenos Aires
Australia	University of Sydney	St. Leonards	New South Wales
Canada	University of Calgary	Calgary	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	North York General Hospital	Toronto	Ontario
Canada	Children's and Women's Hospital	Vancouver	British Columbia
Czech Republic	Centrum lekarske genetiky s.r.o.	Ceske Budejovice
Czech Republic	Imalab	Zlin	Zlinsky kraj
Hungary	Semmelweis University	Budapest
Hungary	Pecs University	Pecs
Ireland	Rotunda Hospital	Dublin
Israel	Rambam Medical Center	Haifa
Italy	U.O. Ostetricia e Ginecologia Laboratorio Sperimentale di Tecniche	Genova
Spain	Hospital Clinic Barcelona - Maternitat Campus	Barcelona	Catalonia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	UVA Medical Center	Charlottesville	Virginia
United States	Northwestern University, FSM	Chicago	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Intermountain Health Care	Murray	Utah
United States	Yale University School of Medicine	New Haven	Connecticut
United States	New Beginnings Perinatal Consultants	Providence	Rhode Island
United States	Women and Infants Hospital	Providence	Rhode Island

Sponsors (2)

Lead Sponsor	Collaborator
Women and Infants Hospital of Rhode Island	Sequenom, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Czech Republic,  Hungary,  Ireland,  Israel,  Italy,  Spain, 

References & Publications (7)

Canick JA, Kloza EM, Lambert-Messerlian GM, Haddow JE, Ehrich M, van den Boom D, Bombard AT, Deciu C, Palomaki GE. DNA sequencing of maternal plasma to identify Down syndrome and other trisomies in multiple gestations. Prenat Diagn. 2012 Aug;32(8):730-4. — View Citation

Canick JA, Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE. The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies. Prenat Diagn. 2013 Jul;33(7):667-74. doi: 10.1002/pd.4126. Epub 2013 Ma — View Citation

Lambert-Messerlian G, Kloza EM, Williams J 3rd, Loucky J, O'Brien B, Wilkins-Haug L, Mahoney MJ, De Biasio P, Borrell A, Ehrich M, van den Boom D, Bombard AT, Deciu C, Palomaki GE. Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assi — View Citation

Mazloom AR, Džakula Ž, Oeth P, Wang H, Jensen T, Tynan J, McCullough R, Saldivar JS, Ehrich M, van den Boom D, Bombard AT, Maeder M, McLennan G, Meschino W, Palomaki GE, Canick JA, Deciu C. Noninvasive prenatal detection of sex chromosomal aneuploidies by — View Citation

Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an — View Citation

Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet — View Citation

Palomaki GE, Kloza EM, Lambert-Messerlian GM, van den Boom D, Ehrich M, Deciu C, Bombard AT, Haddow JE. Circulating cell free DNA testing: are some test failures informative? Prenat Diagn. 2015 Mar;35(3):289-93. doi: 10.1002/pd.4541. Epub 2015 Jan 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The RNA study is an observational trial whose primary aim is to document the performance (sensitivity and specificity) of a laboratory developed test (LDT), using fetal nucleic acid in maternal plasma to identify Down syndrome in early pregnancy.		Within 1st and 2nd trimesters	No
Secondary	The secondary aim is to develop a sample bank to allow documentation of subsequent improvements in the existing LDT or documenting performance of new methodologies.		Late1st and early 2nd trimesters	No