- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04155086
"Circulating Fetal DNA, Pregnancy And Immune Diseases" (AFFEPI)
"Fetal Aneuploidy Screening (21, 18 and 13) by Analysis of Circulating Fetal DNA in a Population of Pregnant Patients With Autoimmune Diseases"
In the plasma of any pregnant patient circulates DNA (also called circulating free DNA). The vast majority of this circulating free DNA is of maternal origin and about 10% is of fetal origin (fetal circulating free DNA). This percentage of fetal circulating free DNA (corresponding to the fetal fraction) increases with gestation.
The pathophysiological hypothesis of this research is that there is a change in the fetal fraction (FF) of fetal circulating free DNA in patients with autoimmune disease (AID). The underlying mechanism would be a massive release of maternal cfDNA responsible for a dilution of fetal cfDNA. This dilution of fetal cfDNA would result in a decrease in the estimate of the foetal fraction of circulating free DNA. However, when the foetal fraction of circulating free DNA is insufficient (4% most often), screening for Trisomy 21 (T21) by fetal circulating free DNA becomes uninterpretable (NC for "non-contributory" result), and cannot be used to assess the risk of T21. In this case, the dose of fetal circulating free DNA can be performed again after 15 days, as the amount of fetal circulating free DNA increases with gestation. In a small number of cases the result will remain NC.
As tests using DNA are becoming more widespread, it is important to prospectively evaluate the results of these tests in the population of patients with AID, which represents about 3 to 5% of pregnant women.
Study Overview
Status
Conditions
Detailed Description
Circulating fetal DNA (cfDNA) in maternal blood is now routinely used for prenatal screening for Down syndrome 21 (T21). In about 1% of cases, the test result is not contributory (NC). The investigator's team recently found, in a retrospective study, an association between the existence of an autoimmune disease (AID) and a high risk of NC. However, this was only a subgroup analysis, requiring confirmation by a dedicated study. Tests using deoxyribonucleic Care (dNCare) are becoming more widespread, so it is important to prospectively evaluate the results of these tests in the population of patients with AID, which represents about 3 to 5% of pregnant women.
The main objective of this study is to compare the rate of NC in a population of patients with DIA to that of a population of patients without MAI when screened for T21 by the cfDNA study in the first trimester of pregnancy.
The secondary objectives are :
- To assess the performance of fetal cfDNA for T21 screening in the population of PATIENTS with AID and to compare them with performance in the non-auto immune disease population.
- To assess the performance of the combined first trimester screening for T21 screening and compare it with those of fetal cfDNA in the population of patients with AID.
- In patients with an NC result, analysis of the distribution of fetal fractions according to the presence and severity of maternal autoimmune pathologies. The distribution will be compared to that of the control population.
- To assess the association between fetal fraction and the occurrence of vascular complications of pregnancy in both groups with and without auto immune disease.
AFFEPI is a prospective multicenter, interventional, exposed/non-exposed cohort study
There are two group :
Exposed group: Any patient with a auto immune disease followed at one of the 14 centres who wants to be screened for T21.
Unexposed group: Patients who do not carry an auto immune disease identified at the interview (no history of auto immune disease; no symptoms suggestive of a auto immune disease).
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Ile De France
-
Clamart, Ile De France, France
- Hôpital Antoine Béclère
-
Contact:
- Alexandre Vivanti
- Phone Number: 01.45.37.44.41
- Email: alexandre.vivanti@aphp.fr
-
Contact:
- Alaxandra Benachi
- Phone Number: 01.45.37.44.76
- Email: alexandra.benachi@aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients in the exposed group:
- Single-fetal pregnancy with a term between 11 and 13-6 weeks of amenorrhea (SA) from spontaneous pregnancy or by medical assistance to procreation.
- Age ≥ 18 years
- Affiliated with a social security or beneficiary scheme
- Desire for natal screening of T21, not yet realized
- Patient with a condition on the following list: [see Chapter 7.2]
Patients in the unexposed group:
- Single-fetal pregnancy with a term between 11 and 13-6 weeks of amenorrhea (SA) from spontaneous pregnancy or by medical assistance to procreation.
- Age ≥ 18 years
- Affiliated with a social security or beneficiary scheme
- Desire for natal screening of T21, not yet realized
- No pathology that meets the list mentioned in the above section
- Clinically asymptomatic patient with no clinical symptoms suggestive of AID: arthralgias, skin or mucous disease, dry syndrome, Raynaud syndrome, purpura.
- Patient respecting frequency pairing
Exclusion Criteria:
- BMI > 35 kg/cm2
- Multiple pregnancy
- No first trimester ultrasound (between 11 and 13-6 SA)
- Screening for unwanted T21
- Patients already included in an interventional research protocol
- Morphological abnormalities on first trimester ultrasound and/or nucal clarity - 3.5mm
- Patient under the protection of justice
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Exposed group (patient with an autoimmunise disease)
Any patient with an autoimmune disease followed at one of the 14 centres who wants to be screened for T21.
|
The detection of the risk of fetal trisomy 21 by blood tests by 2 tests : free fetal DNA circulant analysis and first trimester serum screening
|
Other: Non Exposed group (patient without an autoimmunise disease)
|
The detection of the risk of fetal trisomy 21 by blood tests by 2 tests : free fetal DNA circulant analysis and first trimester serum screening
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The number of inconclusive results of the free circulating fetal DNA test
Time Frame: maximum 15 days after inclusion if the result of the initial analysis is inconclusive. Or maximum 30 days after inclusion if the analysis is realized a second time
|
The detection of the risk of fetal trisomy 21 by 2 blood tests : free circulating analysis fetal DNA and first trimester serum screening.
A result of the free fetal DNA circulant test is rendered as inconclusive when the fetal fraction is strictly less than 4% or the result of the z-scores is not interpretable
|
maximum 15 days after inclusion if the result of the initial analysis is inconclusive. Or maximum 30 days after inclusion if the analysis is realized a second time
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Performance (ability to detect the risk) of fetal DNA for T21 screening in the auto immune disease population. and To compare them with the non-auto immune disease population.
Time Frame: maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or maximum 30 days after inclusion if the analysis is realized a second time
|
The results of free circulating fetal DNA analysis and first trimester serum screening for T21 screening
|
maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or maximum 30 days after inclusion if the analysis is realized a second time
|
Performance (ability to detect the risk) of the combined first trimester serum screening for T21 screening and compare it with those of fetal DNA in auto immune disease population.
Time Frame: maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or maximum 30 days after inclusion if the analysis is realized a second time
|
The results of free circulating fetal DNA analysis and first trimester serum screening for T21 screening
|
maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or maximum 30 days after inclusion if the analysis is realized a second time
|
Distribution of fetal fractions according to the presence and severity of maternal autoimmune pathology
Time Frame: maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or maximum 30 days after inclusion if the analysis is realized a second time
|
Distribution of the results of free circulating fetal DNA analysis and first trimester serum screening for T21 screening in the group of patient with autoimmune disease
|
maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or maximum 30 days after inclusion if the analysis is realized a second time
|
Association between fetal fraction and the occurrence of vascular complications of pregnancy in both groups with and without auto immune disease.
Time Frame: maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or after inclusion if the analysis is realized a second time
|
The detection of the risk of fetal trisomy 21 : Free circulating fetal DNA analysis and first trimester serum screening
|
maximum 15 days after inclusion if the result of the initial analysis is inconclusive, or after inclusion if the analysis is realized a second time
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP180669
- 2019-A01827-50 (Other Identifier: IDRCB number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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