Trisomy 21ISETTRI21NCT01725438
Non Invasive Prenatal Diagnosis of Trisomy 21 by Genetic Analysis of Circulating Fetal Cells
A study testing sample blood in people with Trisomy 21, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The objective of this project is to develop a non-invasive prenatal diagnostic test for trisomy 21 which is reliable, sensitive and cost-effective, and thus, offers an alternative to the currently employed invasive diagnostic tests amniocentesis and chorionic villus sampling. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Trisomy 21
- What is being tested?
- sample blood
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteFrance
- Study dates
- 19 Jun 2012to 31 Dec 2021
- Phase
- Interventional
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pregnant women older than 18 years old
- Pregnant women followed at a prenatal diagnostic centre
- Pregnant woman having a risk (> 1/250) of trisomy 21 based on the combined screening "serological tests/nuchal ultrasonography "
- Sample of blood and cervical smear obtained between the 8th and the 10th WG
- Pregnant women accepting an invasive prenatal diagnosis
- Father of the child agreeing to participate in the clinical study (accepting to give a saliva sample)
- Pregnant women beneficiary of a national insurance program
- Pregnant women and fathers signing an informed consent
Who cannot join
- Pregnant women with combined risk of trisomy 21 < 1/250
- Pregnant women non accepting the invasive prenatal diagnosis
- Pregnant women participating another clinical study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Validation of the ISET Method for the Non Invasive Prenatal Diagnosis of Trisomy 21 by Genetic Analysis of Circulating Trophoblastic Cells
The objective of this project is to develop a non-invasive prenatal diagnostic test for trisomy 21 which is reliable, sensitive and cost-effective, and thus, offers an alternative to the currently employed invasive diagnostic tests amniocentesis and chorionic villus sampling.
Current prenatal screening methods (blood markers and ultrasound) for trisomy 21 (Down syndrome) detect about 90 % of cases and have a false positive rate of > 90 %. The results of these tests are expressed in risks for trisomy 21, the threshold being in France at 1/250. Women exhibiting a higher risk are offered to undergo invasive diagnostic testing, either by amniocentesis or chorionic villus sampling. However, these invasive diagnostic methods are associated with a considerable risk of miscarriage (1-3 %), and thus underline the importance to develop a safe and non-invasive prenatal diagnostic test for trisomy 21. The investigators have planned to assess the clinical impact of a non-invasive prenatal method to detect Trisomy 21 through genetic analysis of circulating trophoblastic cells.
Read the detailed description
The investigators have planned and developed the following approach: fetal cells are first enriched from blood of pregnant women, between 7 and 12 weeks gestation, employing the ISET (isolation by size of epithelial tumor cells) technique. Cells presumed to be of fetal origin are microdissected and subsequently genetically analyzed, using STR markers, to verify their fetal nature. The investigators then plan to test two strategies in order to assess the number of copies of chromosome 21. The first one involves the DNA of a single fetal cell to be analyzed with CGH (comparative genomic hybridization) array. In fact, our team has already developed an application of the metaphase CGH method to single cells isolated by ISET in which we were able to demonstrate the gain of chromosome 21 DNA in single fetal cells isolated from cord blood of a fetus with Down syndrome. The second strategy will be accomplished with the use of quantitative fluorescent PCR analysis of short tandem repeats (STRs), applied to single cells. At least 5-8 highly polymorphic STR markers specific for chromosome 21 will be tested to minimize the effects of a phenomenon called allele drop out, in which one allele fails to amplify, and to maximize the number of triallelic signals for an accurate diagnosis of disomy or trisomy 21.
This survey is performed in collaboration with the Department of Gynaecology-Obstetrics - Reproductive Medicine of Antoine Béclère Hospital in Clamart. The women included in the survey will be taken a 20 ml blood sample and a cervical Pap smear before the invasive test (amniocentesis). The blood sample will be treated by the ISET method within 3 hours after collection and the filter will be stored at - 20°C. The cells obtained by Pap smear will be kept in an appropriate liquid and then treated by the ISET method in the Biochemistry Laboratory of Necker Hospital. The molecular analyses directed to the Trophoblastic cells for the NI-PND of Trisomy 21 will be performed in a blind study.
The instigators have planned to use the ISET method in a blind study including 100 cases of trisomy 21 and 300 control cases with normal caryotype. This study will allow to obtain results with sensitivity higher than 97 % and specificity higher than 99 % (IC 95 % [70-100]). The validation will be obtained by the opening of the blind study and the comparison of results obtained by the invasive method (amniocentesis) and the non-invasive method.
- Conditions
- Trisomy 21
- Being tested
- sample blood
- Keywords
- Circulating Trophoblastic Cells, Non-Invasive Prenatal Diagnosis, Genetic analysis, Trisomy 21, Down's Syndrome
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sample bloodOther
Also called Non Invasive, Prenatal Diagnosis, Trisomy 21
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women accepting an invasive prenatal diagnosis | Experimental | Pregnant women accepting an invasive prenatal diagnosis and a sample blood (non invasive diagnosis) Receives: Other: sample blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
non-invasive method of PND of Trisomy 21.
Clinical validation of a non-invasive method of PND of Trisomy 21.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2012 (estimated)
- Study start19 Jun 2012
- Primary completion31 Mar 2017
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Trisomy 21Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Rarecells, University of Paris 5 - Rene Descartes, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Patrizia Paterlini-Bréchot, MD, PhD, Principal investigator, Necker Enfants Malades Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01725438
- Sponsor's protocol ID
- P100118
- Other IDs
- AOM10123
- Acronym
- ISETTRI21
- Status last verified
- Mar 2026
- First submitted
- 8 Nov 2012
- Last updated
- 3 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, Capron F, Franco D, Pazzagli M, Vekemans M, Lacour B, Brechot C, Paterlini-Brechot P. Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol. 2000 Jan;156(1):57-63. doi: 10.1016/S0002-9440(10)64706-2.
PubMed 10623654Vona G, Beroud C, Benachi A, Quenette A, Bonnefont JP, Romana S, Dumez Y, Lacour B, Paterlini-Brechot P. Enrichment, immunomorphological, and genetic characterization of fetal cells circulating in maternal blood. Am J Pathol. 2002 Jan;160(1):51-8. doi: 10.1016/S0002-9440(10)64348-9.
PubMed 11786398Beroud C, Karliova M, Bonnefont JP, Benachi A, Munnich A, Dumez Y, Lacour B, Paterlini-Brechot P. Prenatal diagnosis of spinal muscular atrophy by genetic analysis of circulating fetal cells. Lancet. 2003 Mar 22;361(9362):1013-4. doi: 10.1016/s0140-6736(03)12798-5.
PubMed 12660061Saker A, Benachi A, Bonnefont JP, Munnich A, Dumez Y, Lacour B, Paterlini-Brechot P. Genetic characterisation of circulating fetal cells allows non-invasive prenatal diagnosis of cystic fibrosis. Prenat Diagn. 2006 Oct;26(10):906-16. doi: 10.1002/pd.1524.
PubMed 16832834Bianchi DW, Simpson JL, Jackson LG, Elias S, Holzgreve W, Evans MI, Dukes KA, Sullivan LM, Klinger KW, Bischoff FZ, Hahn S, Johnson KL, Lewis D, Wapner RJ, de la Cruz F. Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenat Diagn. 2002 Jul;22(7):609-15. doi: 10.1002/pd.347.
PubMed 12124698
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Validation of the ISET Method for the Non Invasive Prenatal Diagnosis of Trisomy 21 by Genetic Analysis of Circulating Trophoblastic Cells
- ClinicalTrials.gov ID
- NCT01725438
- Acronym / sponsor ID
- ISETTRI21 / P100118
- Conditions
- Trisomy 21
- Keywords
- Circulating Trophoblastic Cells, Non-Invasive Prenatal Diagnosis, Genetic analysis, Trisomy 21, Down's Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Rarecells, University of Paris 5 - Rene Descartes, URC-CIC Paris Descartes Necker Cochin
- Study start
- 19 Jun 2012 (actual)
- Primary completion
- 31 Mar 2017 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 12 Nov 2012 (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 objective of this project is to develop a non-invasive prenatal diagnostic test for trisomy 21 which is reliable, sensitive and cost-effective, and thus, offers an alternative to the currently employed invasive diagnostic tests amniocentesis and chorionic villus sampling.
Current prenatal screening methods (blood markers and ultrasound) for trisomy 21 (Down syndrome) detect about 90 % of cases and have a false positive rate of > 90 %. The results of these tests are expressed in risks for trisomy 21, the threshold being in France at 1/250. Women exhibiting a higher risk are offered to undergo invasive diagnostic testing, either by amniocentesis or chorionic villus sampling. However, these invasive diagnostic methods are associated with a considerable risk of miscarriage (1-3 %), and thus underline the importance to develop a safe and non-invasive prenatal diagnostic test for trisomy 21. The investigators have planned to assess the clinical impact of a non-invasive prenatal method to detect Trisomy 21 through genetic analysis of circulating trophoblastic cells.
Detailed description
The investigators have planned and developed the following approach: fetal cells are first enriched from blood of pregnant women, between 7 and 12 weeks gestation, employing the ISET (isolation by size of epithelial tumor cells) technique. Cells presumed to be of fetal origin are microdissected and subsequently genetically analyzed, using STR markers, to verify their fetal nature. The investigators then plan to test two strategies in order to assess the number of copies of chromosome 21. The first one involves the DNA of a single fetal cell to be analyzed with CGH (comparative genomic hybridization) array. In fact, our team has already developed an application of the metaphase CGH method to single cells isolated by ISET in which we were able to demonstrate the gain of chromosome 21 DNA in single fetal cells isolated from cord blood of a fetus with Down syndrome. The second strategy will be accomplished with the use of quantitative fluorescent PCR analysis of short tandem repeats (STRs), applied to single cells. At least 5-8 highly polymorphic STR markers specific for chromosome 21 will be tested to minimize the effects of a phenomenon called allele drop out, in which one allele fails to amplify, and to maximize the number of triallelic signals for an accurate diagnosis of disomy or trisomy 21.
This survey is performed in collaboration with the Department of Gynaecology-Obstetrics - Reproductive Medicine of Antoine Béclère Hospital in Clamart. The women included in the survey will be taken a 20 ml blood sample and a cervical Pap smear before the invasive test (amniocentesis). The blood sample will be treated by the ISET method within 3 hours after collection and the filter will be stored at - 20°C. The cells obtained by Pap smear will be kept in an appropriate liquid and then treated by the ISET method in the Biochemistry Laboratory of Necker Hospital. The molecular analyses directed to the Trophoblastic cells for the NI-PND of Trisomy 21 will be performed in a blind study.
The instigators have planned to use the ISET method in a blind study including 100 cases of trisomy 21 and 300 control cases with normal caryotype. This study will allow to obtain results with sensitivity higher than 97 % and specificity higher than 99 % (IC 95 % [70-100]). The validation will be obtained by the opening of the blind study and the comparison of results obtained by the invasive method (amniocentesis) and the non-invasive method.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pregnant women accepting an invasive prenatal diagnosis | Experimental | Other: sample bloodPregnant women accepting an invasive prenatal diagnosis and a sample blood (non invasive diagnosis) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Pregnant women older than 18 years old
- Pregnant women followed at a prenatal diagnostic centre
- Pregnant woman having a risk (> 1/250) of trisomy 21 based on the combined screening "serological tests/nuchal ultrasonography "
- Sample of blood and cervical smear obtained between the 8th and the 10th WG
- Pregnant women accepting an invasive prenatal diagnosis
Key exclusion criteria (3 listed)
- Pregnant women with combined risk of trisomy 21 < 1/250
- Pregnant women non accepting the invasive prenatal diagnosis
- Pregnant women participating another clinical study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sample bloodAlso: Non Invasive, Prenatal Diagnosis, Trisomy 21 | Other | Pregnant women accepting an invasive prenatal diagnosis |
Primary outcome
non-invasive method of PND of Trisomy 21.
Time frame: 9 months
Clinical validation of a non-invasive method of PND of Trisomy 21.
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 Apr 2026.
- Background: PubMed 10623654Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schutze K, Capron F, Franco D, Pazzagli M, Vekemans M, Lacour B, Brechot C, Paterlini-Brechot P. Isolation by size of epithelial tumor cells : a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol. 2000 Jan;156(1):57-63. doi: 10.1016/S0002-9440(10)64706-2.
- Background: PubMed 11786398Vona G, Beroud C, Benachi A, Quenette A, Bonnefont JP, Romana S, Dumez Y, Lacour B, Paterlini-Brechot P. Enrichment, immunomorphological, and genetic characterization of fetal cells circulating in maternal blood. Am J Pathol. 2002 Jan;160(1):51-8. doi: 10.1016/S0002-9440(10)64348-9.
- Background: PubMed 12660061Beroud C, Karliova M, Bonnefont JP, Benachi A, Munnich A, Dumez Y, Lacour B, Paterlini-Brechot P. Prenatal diagnosis of spinal muscular atrophy by genetic analysis of circulating fetal cells. Lancet. 2003 Mar 22;361(9362):1013-4. doi: 10.1016/s0140-6736(03)12798-5.
- Background: PubMed 16832834Saker A, Benachi A, Bonnefont JP, Munnich A, Dumez Y, Lacour B, Paterlini-Brechot P. Genetic characterisation of circulating fetal cells allows non-invasive prenatal diagnosis of cystic fibrosis. Prenat Diagn. 2006 Oct;26(10):906-16. doi: 10.1002/pd.1524.
- Background: PubMed 12124698Bianchi DW, Simpson JL, Jackson LG, Elias S, Holzgreve W, Evans MI, Dukes KA, Sullivan LM, Klinger KW, Bischoff FZ, Hahn S, Johnson KL, Lewis D, Wapner RJ, de la Cruz F. Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenat Diagn. 2002 Jul;22(7):609-15. doi: 10.1002/pd.347.
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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.
Patrizia Paterlini-Bréchot, MD, PhD principal investigator
Necker Enfants Malades Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sample blood in people with Trisomy 21, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 8 inclusion and 3 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 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
non-invasive method of PND of Trisomy 21. (time frame: 9 months). 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 NCT01725438, which also lists 5 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 Apr 2026.