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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02381457

Registration number

NCT02381457

Ethics application status

Date submitted

2/03/2015

Date registered

6/03/2015

Date last updated

29/01/2021

Titles & IDs

Public title

SNP-based Microdeletion and Aneuploidy RegisTry (SMART)

Scientific title

SNP-based Microdeletion and Aneuploidy RegisTry

Secondary ID [1]

14-024-NPT

Universal Trial Number (UTN)

Trial acronym

SMART

Linked study record

Health condition

Health condition(s) or problem(s) studied:

22q11 Deletion Syndrome

DiGeorge Syndrome

Trisomy 21

Trisomy 18

Trisomy 13

Monosomy X

Sex Chromosome Abnormalities

Cri-du-Chat Syndrome

Angelman Syndrome

Prader-Willi Syndrome

1p36 Deletion Syndrome

Condition category

Condition code

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Mental Health

Learning disabilities

Neurological

Other neurological disorders

Human Genetics and Inherited Disorders

Down's syndrome

Cardiovascular

Other cardiovascular diseases

Other

Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure

Study type

Observational [Patient Registry]

Patient registry

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Pregnancies undergoing prenatal microdeletion screening - Pregnant women undergoing non-invasive prenatal screening for microdeletion and aneuploidy syndromes.

No drug will be administrated, this cohort will undergo a non invasive prenatal blood test and then follow up data and specimens will be collected for research analysis.

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity

Timepoint [1]

3 years

Secondary outcome [1]

Combined microdeletion syndrome screening test performance

Timepoint [1]

3 years

Secondary outcome [2]

No call rate

Timepoint [2]

3 years

Secondary outcome [3]

Low fetal fraction aneuploidy risk refinement

Timepoint [3]

3 years

Secondary outcome [4]

Placental mosaicism exploration

Timepoint [4]

3 years

Secondary outcome [5]

Placental complications exploration

Timepoint [5]

3 years

Eligibility

Key inclusion criteria

* Singleton pregnancy
* Receiving Panorama prenatal screening test for both microdeletions (at least 22q11.2) and aneuploidy
* Planned hospital delivery
* Gestational age of = 9 weeks, 0 days based on clinical information and evaluation.
* Able to provide informed consent

Minimum age

18 Years

Maximum age

48 Years

Sex

Females

Can healthy volunteers participate?

Yes

Key exclusion criteria

* Received results of the Panorama test prior to enrollment
* Organ transplant recipient
* Egg donor used

Study design

Purpose

Duration

Selection

Timing

Prospective

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

1/04/2015

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

1/06/2020

Sample size

Target

Accrual to date

Final

20960

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Prince Alfred - Camperdown

Recruitment postcode(s) [1]

2050 - Camperdown

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

New Jersey

Country [3]

United States of America

State/province [3]

New York

Country [4]

United States of America

State/province [4]

Texas

Country [5]

United States of America

State/province [5]

Utah

Country [6]

Ireland

State/province [6]

Dublin

Country [7]

Spain

State/province [7]

Barcelona

Country [8]

Sweden

State/province [8]

Gothenburg

Country [9]

United Kingdom

State/province [9]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Natera, Inc.

Address

Country

Other collaborator category [1]

Other

Name [1]

George Washington University

Address [1]

Country [1]

Other collaborator category [2]

Other

Name [2]

University of California, San Francisco

Address [2]

Country [2]

Other collaborator category [3]

Other

Name [3]

Montefiore Medical Center

Address [3]

Country [3]

Other collaborator category [4]

Other

Name [4]

Children's Hospital of Philadelphia

Address [4]

Country [4]

Ethics approval

Ethics application status

Summary

Brief summary

This multi-center prospective observational study is designed to track birth outcomes and perinatal correlates to the Panorama prenatal screening test in the general population among ten thousand women who present clinically and elect Panorama microdeletion and aneuploidy screening as part of their routine care. The primary objective is to evaluate the performance of Single Nucleotide Polymorphism (SNP)-based Non Invasive Prenatal Testing (NIPT) for 22q11.2 microdeletion (DiGeorge syndrome) in this large cohort of pregnant women. This will be done by performing a review of perinatal medical records and obtaining biospecimens after birth to perform genetic diagnostic testing for 22q11.2 deletion. Results from the follow-up specimens will be compared to those obtained by the Panorama screening test to determine test performance. Specific test performance parameters will include: PPV, specificity, and sensitivity.

Trial website

https://clinicaltrials.gov/study/NCT02381457

Trial related presentations / publications

American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013 Dec;122(6):1374-7. doi: 10.1097/01.AOG.0000438962.16108.d1.
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):210-218. doi: 10.1097/AOG.0000000000000363.
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.
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.
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.
Benn P, Cuckle H, Pergament E. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012 Jun;119(6):1270; author reply 1270-1. doi: 10.1097/AOG.0b013e318258c401. No abstract available.
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.
Sparks AB, Struble CA, Wang ET, Song K, Oliphant A. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012 Apr;206(4):319.e1-9. doi: 10.1016/j.ajog.2012.01.030. Epub 2012 Jan 26.
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.
Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat Diagn. 2013 Jun;33(6):575-9. doi: 10.1002/pd.4103. Epub 2013 Apr 24.
Nicolaides KH, Syngelaki A, del Mar Gil M, Quezada MS, Zinevich Y. Prenatal detection of fetal triploidy from cell-free DNA testing in maternal blood. Fetal Diagn Ther. 2014;35(3):212-7. doi: 10.1159/000355655. Epub 2013 Oct 10.
Samango-Sprouse C, Banjevic M, Ryan A, Sigurjonsson S, Zimmermann B, Hill M, Hall MP, Westemeyer M, Saucier J, Demko Z, Rabinowitz M. SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Prenat Diagn. 2013 Jul;33(7):643-9. doi: 10.1002/pd.4159. Epub 2013 Jun 20.
Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.
Wapner RJ, Babiarz JE, Levy B, Stosic M, Zimmermann B, Sigurjonsson S, Wayham N, Ryan A, Banjevic M, Lacroute P, Hu J, Hall MP, Demko Z, Siddiqui A, Rabinowitz M, Gross SJ, Hill M, Benn P. Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes. Am J Obstet Gynecol. 2015 Mar;212(3):332.e1-9. doi: 10.1016/j.ajog.2014.11.041. Epub 2014 Dec 2.
Vora NL, O'Brien BM. Noninvasive prenatal testing for microdeletion syndromes and expanded trisomies: proceed with caution. Obstet Gynecol. 2014 May;123(5):1097-1099. doi: 10.1097/AOG.0000000000000237.
Taglauer ES, Wilkins-Haug L, Bianchi DW. Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease. Placenta. 2014 Feb;35 Suppl(Suppl):S64-8. doi: 10.1016/j.placenta.2013.11.014. Epub 2013 Dec 1.
Knight M, Redman CW, Linton EA, Sargent IL. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol. 1998 Jun;105(6):632-40. doi: 10.1111/j.1471-0528.1998.tb10178.x.
Dar P, Curnow KJ, Gross SJ, Hall MP, Stosic M, Demko Z, Zimmermann B, Hill M, Sigurjonsson S, Ryan A, Banjevic M, Kolacki PL, Koch SW, Strom CM, Rabinowitz M, Benn P. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. Am J Obstet Gynecol. 2014 Nov;211(5):527.e1-527.e17. doi: 10.1016/j.ajog.2014.08.006. Epub 2014 Aug 8.
Amos-Landgraf JM, Ji Y, Gottlieb W, Depinet T, Wandstrat AE, Cassidy SB, Driscoll DJ, Rogan PK, Schwartz S, Nicholls RD. Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am J Hum Genet. 1999 Aug;65(2):370-86. doi: 10.1086/302510.
Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, Pearson GD, Wapner RJ, Varner MW, Thorp JM Jr, Mercer BM, Peaceman AM, Ramin SM, Carpenter MW, Samuels P, Sciscione A, Harper M, Smith WJ, Saade G, Sorokin Y, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010 Apr 8;362(14):1282-91. doi: 10.1056/NEJMoa0908056.
Tranquilli AL, Emanuelli M. The thrombophilic fetus. Med Hypotheses. 2006;67(5):1226-9. doi: 10.1016/j.mehy.2006.04.046. Epub 2006 Jul 11.
Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med. 2003 Mar;13(3):175-90. doi: 10.1080/jmf.13.3.175.190.
Dar P, Jacobsson B, MacPherson C, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Haeri S, Silver R, Vohra N, Hyett J, Clunie G, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Malone C, Hallingstrom M, Klugman S, Clifton R, Kao C, Hakonarson H, Norton ME. Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation. Am J Obstet Gynecol. 2022 Aug;227(2):259.e1-259.e14. doi: 10.1016/j.ajog.2022.01.019. Epub 2022 Jan 25.
Dar P, Jacobsson B, Clifton R, Egbert M, Malone F, Wapner RJ, Roman AS, Khalil A, Faro R, Madankumar R, Edwards L, Strong N, Haeri S, Silver R, Vohra N, Hyett J, Demko Z, Martin K, Rabinowitz M, Flood K, Carlsson Y, Doulaveris G, Daly S, Hallingstrom M, MacPherson C, Kao C, Hakonarson H, Norton ME. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. Am J Obstet Gynecol. 2022 Jul;227(1):79.e1-79.e11. doi: 10.1016/j.ajog.2022.01.002. Epub 2022 Jan 13.

Public notes

Contacts

Principal investigator

Name

Peer Dar, MD

Address

Montefiore Medical Center

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Type	Citations or Other Details
Journal	Pergament E, Cuckle H, Zimmermann B, Banjevic M, S... [More Details]
Journal	Ehrich M, Deciu C, Zwiefelhofer T, Tynan JA, Cagas... [More Details]
Journal	Palomaki GE, Kloza EM, Lambert-Messerlian GM, Hadd... [More Details]
Journal	Sehnert AJ, Rhees B, Comstock D, de Feo E, Heilek ... [More Details]
Journal	Benn P, Cuckle H, Pergament E. Genome-wide fetal a... [More Details]
Journal	Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian... [More Details]
Journal	Sparks AB, Struble CA, Wang ET, Song K, Oliphant A... [More Details]
Journal	Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, ... [More Details]
Journal	Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Ma... [More Details]
Journal	Nicolaides KH, Syngelaki A, del Mar Gil M, Quezada... [More Details]
Journal	Samango-Sprouse C, Banjevic M, Ryan A, Sigurjonsso... [More Details]
Journal	Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Z... [More Details]
Journal	Wapner RJ, Babiarz JE, Levy B, Stosic M, Zimmerman... [More Details]
Journal	Vora NL, O'Brien BM. Noninvasive prenatal testing ... [More Details]
Journal	Taglauer ES, Wilkins-Haug L, Bianchi DW. Review: c... [More Details]
Journal	Knight M, Redman CW, Linton EA, Sargent IL. Sheddi... [More Details]
Journal	Dar P, Curnow KJ, Gross SJ, Hall MP, Stosic M, Dem... [More Details]
Journal	Amos-Landgraf JM, Ji Y, Gottlieb W, Depinet T, Wan... [More Details]
Journal	Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, ... [More Details]
Journal	Tranquilli AL, Emanuelli M. The thrombophilic fetu... [More Details]
Journal	Faiz AS, Ananth CV. Etiology and risk factors for ... [More Details]

Results not provided in https://clinicaltrials.gov/study/NCT02381457

Trial Review

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02381457