High Risk Multiple Gestation Study

Trisomy 21 Clinical Trial

Official title:

Development of Non-invasive Prenatal Diagnostic Test for Multiple Gestation Pregnancies Based on Fetal DNA Isolated From Maternal Blood

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02278874
• Other study ID #: 13-016B-NPT
• Status: Completed
• Start date: August 2014
• Est. completion date: March 2019

Study information

• Verified date: June 2019
• Source: Natera, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objectives of the clinical study are to demonstrate the accuracy of our proprietary algorithm method to determine the genetic health of the developing fetuses in a multiple gestation pregnancy from a maternal blood sample. The long term goal of this study will be the development of a method of minimally invasive prenatal diagnosis that has a higher sensitivity and lower false positive rate in the intended population (e.g. multiple gestation pregnancies) than other currently available screening tests.

This will result in fewer unnecessary amniocenteses and Chorionic Villus Sample (CVS) procedures, which are associated with a risk of miscarriage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: March 2019
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 or older at enrollment

• Clinically confirmed multiple gestation pregnancy

• Pregnancy at high risk for genetic aneuploidy as defined below:

• Confirmed positive aneuploidy by invasive testing

• Non invasive prenatal testing "high risk" result

• Serum screening risk of greater than 1:100

• Ultrasound abnormalities indicative of aneuploidy

• Structural abnormality of the posterior fossa

• Holoprosencephaly

• Structural cardiac anomaly

• Omphalocele

• Nuchal translucency greater than or equal to 3.5 mm or a nuchal fold greater Hydrops of unknown etiology

• Age = 38 years at delivery (if serum screening risk is not less than 1:100)

• Gestational age between = 9 weeks, 0 days and =26 weeks 0 days by best obstetrical estimate

• Able to provide informed consent

Exclusion Criteria:

• Women carrying singleton pregnancy

• Surrogate or egg donor used

Related Conditions & MeSH terms

• Chromosome Aberrations
• Chromosome Disorders
• Congenital Abnormalities
• Down Syndrome
• Sex Chromosome Aberrations
• Sex Chromosome Abnormalities
• Trisomy 13
• Trisomy 18
• Trisomy 21

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Long Island Jewish Medical Center	Glen Cove	New York
United States	Mt. Sinai Hospital	New York	New York

Sponsors (5)

Lead Sponsor	Collaborator
Natera, Inc.	Long Island Jewish Medical Center, Montefiore Medical Center, MOUNT SINAI HOSPITAL, Tufts Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (8)

Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP; MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012 May;119(5):890-901. doi: 10.1097/AOG.0b013e31824fb482. Erratum in: Obstet Gynecol. 2012 Oct;120(4):957. — View Citation

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. — View Citation

Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagasan L, Tim R, Lu V, McCullough R, McCarthy E, Nygren AO, Dean J, Tang L, Hutchison D, Lu T, Wang H, Angkachatchai V, Oeth P, Cantor CR, Bombard A, van den Boom D. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol. 2011 Mar;204(3):205.e1-11. doi: 10.1016/j.ajog.2010.12.060. Epub 2011 Feb 18. — View Citation

Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, Rodriguez MH, Williams J 3rd, Mitchell ME, Adair CD, Lee H, Jacobsson B, Tomlinson MW, Oepkes D, Hollemon D, Sparks AB, Oliphant A, Song K. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012 Aug;207(2):137.e1-8. doi: 10.1016/j.ajog.2012.05.021. Epub 2012 Jun 1. — 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 international collaborative study. Genet Med. 2012 Mar;14(3):296-305. doi: 10.1038/gim.2011.73. Epub 2012 Feb 2. — 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 Med. 2011 Nov;13(11):913-20. doi: 10.1097/GIM.0b013e3182368a0e. — View Citation

Pergament E, Cuckle H, Zimmermann B, Banjevic M, Sigurjonsson S, Ryan A, Hall MP, Dodd M, Lacroute P, Stosic M, Chopra N, Hunkapiller N, Prosen DE, McAdoo S, Demko Z, Siddiqui A, Hill M, Rabinowitz M. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol. 2014 Aug;124(2 Pt 1):210-8. doi: 10.1097/AOG.0000000000000363. — View Citation

Sehnert AJ, Rhees B, Comstock D, de Feo E, Heilek G, Burke J, Rava RP. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem. 2011 Jul;57(7):1042-9. doi: 10.1373/clinchem.2011.165910. Epub 2011 Apr 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Screening capability of proprietary algorithm in the form of a risk results classified as positive result for aneuploidy, negative result for aneuploidy or 'no call.'	The primary outcome will be to confirm the diagnostic capability of NATUS risk results (a risk score eg 1:100) classified as positive result for aneuploidy, negative result for aneuploidy or 'no call.' The outcome will be determined as a risk score given for samples collected. This outcome will be compared to the diagnostic testing results of ploidy status.; The chromosomal status will be determined from the CVS or amniocentesis results, if available. A cheek swab or saliva sample will be collected from live-born children if there are no CVS or amniocentesis results. This will be used to determine the true ploidy status of the fetuses.	4 years

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