Down SyndromeRNANCT00877292
A New Prenatal Blood Test for Down Syndrome
An observational study of Down Syndrome and Trisomy 21, run by Women and Infants Hospital of Rhode Island at 27 sites in 10 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Down Syndrome, Trisomy 21
- How many people
- 4,664 participants
- Where
- 27 sitesin 10 countries
- Study dates
- Feb 2009to May 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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).
Who cannot join
- Nonpregnant women and women at relatively low risk for a Down syndrome baby.
Trial locations and contacts
27 sites in 10 countries.
27 sites in 10 countries
United States12 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Brigham and Women's Hospital
Boston, Massachusetts, 02115
UVA Medical Center
Charlottesville, Virginia, 22908
Northwestern University, FSM
Chicago, Illinois, 60611
Henry Ford Hospital
Detroit, Michigan, 48202
Baylor College of Medicine
Houston, Texas, 77021-2024
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Intermountain Health Care
Murray, Utah, 84107-5701
Yale University School of Medicine
New Haven, Connecticut, 06520
New Beginnings Perinatal Consultants
Providence, Rhode Island, 02905
Women and Infants Hospital
Providence, Rhode Island, 02905
Canada4 sites
University of Calgary
Calgary, Alberta, T2N 4N1
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
North York General Hospital
Toronto, Ontario, M2K 1E1
Children's and Women's Hospital
Vancouver, British Columbia
Argentina2 sites
Center for Medical Education and Clinical Investiagtion
Buenos Aires, 1431
Sociedad Italiana de Beneficencia en Buenos Aires - Hospital Italiano
Buenos Aires, C1181ACH
Czechia2 sites
Centrum lekarske genetiky s.r.o.
České Budějovice, 370 01
Imalab
Zlín, Zlín, 76001
Italy1 site
U.O. Ostetricia e Ginecologia Laboratorio Sperimentale di Tecniche
Genova, 16147
Spain1 site
Hospital Clinic Barcelona - Maternitat Campus
Barcelona, Catalonia, 08020
About this study
Official title: The RNA (RNA-Based Noninvasive Aneuploidy) Study
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.
Read the detailed 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.
- Conditions
- Down Syndrome, Trisomy 21
- Keywords
- Down Syndrome, trisomy 21, prenatal testing, pregnant women
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Down syndrome | Women having CVS or amniocentesis who, as a group, have a high prevalence of Down syndrome. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Late1st and early 2nd trimesters
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study startFeb 2009
- Primary completionJan 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 4,664 participants (actual)
Sponsor and investigators
- Lead sponsor
- Women and Infants Hospital of Rhode Island
- Sponsor type
- University, hospital or other
- Collaborators
- Sequenom, Inc.
- Responsible party
- Principal investigator, Glenn E. Palomaki PhD, Women and Infants Hospital of Rhode Island
- Investigators
- Barbara O'Brien, MD, Principal investigator, Women and Infants Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00877292
- Sponsor's protocol ID
- 09-0004
- Acronym
- RNA
- Status last verified
- Jun 2015
- First submitted
- 6 Apr 2009
- Last updated
- 3 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22281937Canick 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.
PubMed 22585317Palomaki 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.
PubMed 25449554Lambert-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.
PubMed 24091801Mazloom 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.
PubMed 23592550Canick 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.
PubMed 23592541Palomaki 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.
PubMed 22005709Palomaki 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.
PubMed 25834952Kloza 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.
PubMed 25204423
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The RNA (RNA-Based Noninvasive Aneuploidy) Study
- ClinicalTrials.gov ID
- NCT00877292
- Acronym / sponsor ID
- RNA / 09-0004
- Conditions
- Down Syndrome, Trisomy 21
- Keywords
- Down Syndrome, trisomy 21, prenatal testing, pregnant women
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4,664 participants (actual)
- Lead sponsor
- Women and Infants Hospital of Rhode IslandUniversity, hospital or other
- Collaborators
- Sequenom, Inc.
- Study start
- Feb 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 7 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Down syndrome | – | –Women having CVS or amniocentesis who, as a group, have a high prevalence of Down syndrome. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (7 listed)
- 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:
- 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).
Key exclusion criteria (1 listed)
- Nonpregnant women and women at relatively low risk for a Down syndrome baby.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Time frame: Within 1st and 2nd trimesters
1 secondary outcome
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.
Time frame: Late1st and early 2nd trimesters
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2015.
- Results publication: PubMed 22281937Palomaki 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.
- Results publication: PubMed 22585317Canick 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.
- Results publication: PubMed 25449554Palomaki 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.
- Results publication: PubMed 24091801Lambert-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.
- Results publication: PubMed 23592550Mazloom 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.
- Results publication: PubMed 23592541Canick 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.
- Results publication: PubMed 22005709Palomaki 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.
- Derived from this study: PubMed 25834952Palomaki 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.
- Derived from this study: PubMed 25204423Kloza 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara O'Brien, MD principal investigator
Women and Infants Hospital
27 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Down Syndrome and Trisomy 21, run by Women and Infants Hospital of Rhode Island at 27 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada, Argentina, Czechia, Hungary and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Within 1st and 2nd trimesters). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00877292, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2015.