A New Prenatal Blood Test for Down Syndrome

NCT00877292 | Completed

• 1 other identifier: 09-0004
• Study Type: observational
• Target: 4,664
• Locations: 10 countries
• Sites: 27

Brief 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.

Conditions

Down Syndrome; Trisomy 21

Keywords

Down Syndrome; trisomy 21; prenatal testing; pregnant women

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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

Study Arms (1)

Down syndrome

Women having CVS or amniocentesis who, as a group, have a high prevalence of Down syndrome.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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:
• the combined test at 10 to 13 weeks (NT, PAPP-A and hCG)
• the second trimester quadruple test at 15 to 18 weeks gestation
• 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).

You may not qualify if:

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

Sponsors & Collaborators

• Women and Infants Hospital of Rhode Island: lead
• Sequenom, Inc.: collaborator

Study Sites (27)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Northwestern University, FSM

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

New Beginnings Perinatal Consultants

Providence, Rhode Island, 02905, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Baylor College of Medicine

Houston, Texas, 77021-2024, United States

Location

Intermountain Health Care

Murray, Utah, 84107-5701, United States

Location

UVA Medical Center

Charlottesville, Virginia, 22908, United States

Location

Center for Medical Education and Clinical Investiagtion

Buenos Aires, 1431, Argentina

Location

Sociedad Italiana de Beneficencia en Buenos Aires - Hospital Italiano

Buenos Aires, C1181ACH, Argentina

Location

University of Sydney

St Leonards, New South Wales, 2065, Australia

Location

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

Location

Children's and Women's Hospital

Vancouver, British Columbia, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

Location

Imalab

Zlín, Zlín, 76001, Czechia

Location

Centrum lekarske genetiky s.r.o.

České Budějovice, 370 01, Czechia

Location

Semmelweis University

Budapest, Hungary

Location

Pecs University

Pécs, 17, Hungary

Location

Rotunda Hospital

Dublin, Ireland

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

U.O. Ostetricia e Ginecologia Laboratorio Sperimentale di Tecniche

Genova, 16147, Italy

Location

Hospital Clinic Barcelona - Maternitat Campus

Barcelona, Catalonia, 08020, Spain

Location

Related Publications (9)

• 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 international collaborative study. Genet Med. 2012 Mar;14(3):296-305. doi: 10.1038/gim.2011.73. Epub 2012 Feb 2.

  PMID: 22281937 RESULT

• 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. doi: 10.1002/pd.3892. Epub 2012 May 14.

  PMID: 22585317 RESULT

• 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.

  PMID: 25449554 RESULT

• 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 assisted reproductive technologies. Genet Med. 2014 May;16(5):419-22. doi: 10.1038/gim.2013.149. Epub 2013 Oct 3.

  PMID: 24091801 RESULT

• Mazloom AR, Dzakula Z, 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 sequencing circulating cell-free DNA from maternal plasma. Prenat Diagn. 2013 Jun;33(6):591-7. doi: 10.1002/pd.4127.

  PMID: 23592550 RESULT

• 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 May 31.

  PMID: 23592541 RESULT

• 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 Med. 2011 Nov;13(11):913-20. doi: 10.1097/GIM.0b013e3182368a0e.

  PMID: 22005709 RESULT

• Palomaki GE, Ashwood ER, Best RG, Lambert-Messerlian G, Knight GJ. Is maternal plasma DNA testing impacting serum-based screening for aneuploidy in the United States? Genet Med. 2015 Nov;17(11):897-900. doi: 10.1038/gim.2015.39. Epub 2015 Apr 2.

  PMID: 25834952 DERIVED

• Kloza EM, Haddow PK, Halliday JV, O'Brien BM, Lambert-Messerlian GM, Palomaki GE. Evaluation of patient education materials: the example of circulating cell free DNA testing for aneuploidy. J Genet Couns. 2015 Apr;24(2):259-66. doi: 10.1007/s10897-014-9758-8. Epub 2014 Sep 10.

  PMID: 25204423 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Fetal RNA and DNA in maternal plasma

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Barbara O'Brien, MD

  Women and Infants Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicpal Investigator

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 7, 2009
• Study Start: February 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 3, 2015

Record last verified: 2015-06

Locations

IT (1); CZ (2); AR (2); AU (1); CA (4); US (12); IE (1); IL (1); ES (1); HU (2)