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SNP-based Microdeletion and Aneuploidy RegisTry (SMART) (SMART)

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ClinicalTrials.gov Identifier: NCT02381457
Recruitment Status : Recruiting
First Posted : March 6, 2015
Last Update Posted : September 25, 2017
Sponsor:
Collaborators:
George Washington University
University of California, San Francisco
Montefiore Medical Center
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Natera, Inc.

Study Description
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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.

Condition or disease
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

Detailed Description:

The primary objective is to determine in a prospective study the performance of SNP based NIPT for the 22q11.2 microdeletion (DiGeorge syndrome) in a large cohort of pregnant women clinically opting for this form of screening. Specific test performance parameters will include: positive predictive value (PPV), specificity, and sensitivity.

Secondary objectives include:

  1. Determine the test performance (PPV, specificity) of SNP based NIPT for detecting other microdeletion syndromes available in the Panorama microdeletion panel (e.g., 1p36 deletion, Cri-du-chat, Prader-Willi, and Angelman) individually and all combined (including 22q11.2). Given the incidences of <1:5000, the confidence intervals are expected to be large.
  2. Determine the failure ('no call') rate for the Next-generation Aneuploidy Test Using SNPs (NATUS) method for 22q11.2 detection, as well as for aneuploidy.
  3. Determine whether a more precise risk for aneuploidy can be generated in the setting of low fetal fraction by incorporating maternal BMI (adjusted fetal fraction percentile).
  4. Assess whether low fetal fraction is associated with specific ultrasound findings that may indicate aneuploidy (e.g. triploidy, trisomy 13 and 18).
  5. Investigate the relationship between NIPT and sonographic (nuchal translucency and anatomy survey) markers and serum markers from 1st and 2nd trimester aneuploidy screening.
  6. Determine sensitivity, specificity, and PPV for chromosomal aneuploidies and sex chromosome abnormalities.
  7. Perform detailed assessment of false positive aneuploidy samples to better understand sources of error, including placental studies to further refine issues surrounding mosaicism as NIPT represents circulating placental DNA.
  8. Investigate any relationships between circulating placental DNA (fetal fraction) or other test parameters including potential genotypic markers, and outcomes related to abnormal placentation (including but not limited to preeclampsia, small for gestational age and morbidly adherent placenta).
  9. Investigate other risk factors that may impact risk assessment for microdeletions including sonographic findings consistent with 22q11.2 (cardiac anomalies and thymus size).

Study Design
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Study Type : Observational [Patient Registry]
Estimated Enrollment : 10000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: SNP-based Microdeletion and Aneuploidy RegisTry
Study Start Date : April 2015
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort
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.


Outcome Measures
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Primary Outcome Measures :
  1. 22q11.2 Snp-based non-invasive prenatal screening test performance, including positive predictive value (PPV), specificity, and sensitivity [ Time Frame: 3 years ]
    To determine in a prospective study the performance of SNP based NIPT for the 22q11.2 microdeletion (DiGeorge syndrome) in a large cohort of pregnant women clinically opting for this form of screening.


Secondary Outcome Measures :
  1. Combined microdeletion syndrome screening test performance [ Time Frame: 3 years ]
    Determine the test performance (PPV, specificity) of SNP based NIPT for detecting other microdeletion syndromes available in the Panorama microdeletion panel (e.g., 1p36 deletion, Cri-du-chat, Prader-Willi, and Angelman) individually and all combined (including 22q11.2). Given the incidences of <1:5000, the confidence intervals are expected to be large.

  2. No call rate [ Time Frame: 3 years ]
    Determine the failure ('no call') rate for the NATUS method for 22q11.2 detection, as well as for aneuploidy.

  3. Low fetal fraction aneuploidy risk refinement [ Time Frame: 3 years ]
    Determine whether a more precise risk for aneuploidy can be generated in the setting of low fetal fraction by incorporating maternal BMI (adjusted fetal fraction percentile), or whether low fetal fraction is associated with specific ultrasound findings that may indicate aneuploidy (e.g. triploidy, trisomy 13 and 18).

  4. Placental mosaicism exploration [ Time Frame: 3 years ]
    Perform detailed assessment of false positive aneuploidy samples to better understand sources of error, including placental studies to further refine issues surrounding mosaicism as NIPT represents circulating placental DNA.

  5. Placental complications exploration [ Time Frame: 3 years ]
    Investigate any relationships between circulating placental DNA (fetal fraction) or other test parameters including potential genotypic markers, and outcomes related to abnormal placentation (including but not limited to preeclampsia, small for gestational age and morbidly adherent placenta).


Biospecimen Retention:   Samples With DNA
  • Maternal residual blood sample
  • Placental tissue
  • Child dried blood spot
  • Child buccal sample

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 48 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women
Criteria

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

Exclusion Criteria:

  • Received results of the Panorama test prior to enrollment
  • Organ transplant recipient
  • Egg donor used
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02381457


Contacts
Contact: Melissa Schirmer, MS 650-249-9090 ext 696 research@natera.com
Contact: Ella Zha 650-249-9090 ext 1770 czha@natera.com

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Kao Thao    415-514-0502      
United States, New Jersey
St. Peter's University Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Shoan Davis    732-745-8600 ext 6078      
Principal Investigator: Edward Guzman, MD         
United States, New York
Complete Women's Healthcare Active, not recruiting
Garden City, New York, United States, 11530
North Shore University Hospital Recruiting
Manhasset, New York, United States, 11030
Contact: Stephanie Augustine    516-532-2464      
Madonna Perinatal Recruiting
Mineola, New York, United States, 11501
Contact: Barbara Feldman    516-747-4616      
Principal Investigator: David Bergman, MD         
Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Principal Investigator: Rajeevi Madankumar, MD         
New York University Recruiting
New York, New York, United States, 10016
Contact: Keith Bonus    212-263-7021      
Principal Investigator: Ashely Roman, MD         
Icahn School of Medicine Mt Sinai Recruiting
New York, New York, United States, 10029
Contact: Julie Cadet, MPH    212-241-5413      
Principal Investigator: Noel Stone, MD         
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Caroline Torres, CCRC    212-305-2158      
Principal Investigator: Ronald Wapner, MD         
Montefiore Medical Center Recruiting
New York, New York, United States, 10461
Contact: Melissa Hudson    718-405-8214      
Principal Investigator: Peer Dar, MD         
Suffolk OB Recruiting
Port Jefferson, New York, United States, 11777
Contact: Maureen Hurst    631-656-4060      
Principal Investigator: Lance Edwards, MD         
United States, Texas
North Austin Maternal Fetal Medicine Recruiting
Austin, Texas, United States, 78758
Contact: Caroline Gleason, LVN    512-493-6905      
Principal Investigator: Sina Haeri, MD         
Zeid Women's Health Center Recruiting
Longview, Texas, United States, 75601
Contact: Trisha Malone         
Principal Investigator: Yasser Zeid, MD         
United States, Utah
University of Utah Active, not recruiting
Salt Lake City, Utah, United States, 84132
Australia, New South Wales
Royal Prince Alfred Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Jane Tooher         
Principal Investigator: Jon Hyett, MD         
Ireland
Royal College Surgeons in Ireland Recruiting
Dublin, Ireland, 1
Contact: Lisa McSweeney    00353 (86) 3798087      
Principal Investigator: Fergal Malone, MD         
Sub-Investigator: Karen Flood, MD         
Sweden
Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden, SE-416 85
Contact: Karin Kalin    46313436731      
Principal Investigator: Bo Jacobsson, MD         
United Kingdom
St. George University Hospital Recruiting
London, United Kingdom, SW17 0QT
Contact: Yaa Acheampong    +44 20 8725 0071/3664.      
Principal Investigator: Asma Khalil, MD         
Sub-Investigator: Baskaran Thilaganathan, MD         
Sponsors and Collaborators
Natera, Inc.
George Washington University
University of California, San Francisco
Montefiore Medical Center
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Peer Dar, MD Montefiore Medical Center
Principal Investigator: Mary Norton, MD University of California, San Francisco
More Information
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Additional Information:
1p36 Deletion Syndrome  This link exits the ClinicalTrials.gov site
Angelman Syndrome  This link exits the ClinicalTrials.gov site
Cri-du-chat Syndrome  This link exits the ClinicalTrials.gov site

Publications of Results:

Other Publications:

Responsible Party: Natera, Inc.
ClinicalTrials.gov Identifier: NCT02381457     History of Changes
Other Study ID Numbers: 14-024-NPT
First Posted: March 6, 2015    Key Record Dates
Last Update Posted: September 25, 2017
Last Verified: September 2017

Keywords provided by Natera, Inc.:
Microdeletion Syndrome
Aneuploidy
22q
Non-Invasive Prenatal Screening
DiGeorge Syndrome

Additional relevant MeSH terms:
Syndrome
Prader-Willi Syndrome
Trisomy
Aneuploidy
Down Syndrome
Angelman Syndrome
DiGeorge Syndrome
Chromosome Aberrations
Chromosome Disorders
Monosomy
Sex Chromosome Aberrations
22q11 Deletion Syndrome
Cri-du-Chat Syndrome
Disease
Pathologic Processes
 Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders
Chromosome Duplication
Movement Disorders
Central Nervous System Diseases
Craniofacial Abnormalities
Musculoskeletal Abnormalities