- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03743948
NIPD of CFTC by WGA Coupled to Mini-exome Sequencing (DIAFEXOME)
Non Invasive Prenatal Diagnosis on Isolated Circulating Fetal Trophoblastic Cells (CFTC) for Monogenic Diseases
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Context:
Non Invasive Prenatal Diagnosis (NIPD), based on the analysis of circulating cell-free fetal DNA (cff-DNA) is very promising for early diagnosis of monogenic diseases. Such an approach is a safer alternative to invasive methods of prenatal testing (amniocentesis or choriocentesis) which entails a significant risk of miscarriage (0.5%-1%). However, technical issues related to the characteristics of cff-DNA remain, and NIPD techniques require long process development which are specific for a gene and/or a particular mutation.
Objectives:
The objective of this study is to complete our offer of NIPD by developing an approach on isolated Circulating Trophoblastic Fetal Cells (CFTC) adapted to the analysis of the genes and mutations involved in current prenatal testing requests.
Methodology :
The blood of pregnant women from 9 weeks of gestation for which a prenatal testing is requested will be collected.
CFTC isolation using Circulating Tumor Cells (CTCs) enrichment systems will be followed by whole genome amplification coupled to mini-exome sequencing and bioinformatic filtering that will be specific to the prenatal testing indication.
The study will be carried out in 2 stages:
- analytical validation of the method by studying the data quality of the sequencing of targeted genes that are frequently subject to prenatal testing (see prenatal testing diseases list from "ABM DPN 2014" in Appendix 2).
- clinical evaluation of the method by checking the concordance between the results obtained by our new approach versus those obtained by standard procedure (amniocentesis or choriocentesis) for 15 pregnant women.
Expected results and perspectives:
The purpose of this study is to establish the proof of concept of a semi-universal NIPD method based on a simple maternal blood test that could be applied on most rare diseases requiring prenatal testing.
This NIPD approach would reduce the number of invasive procedures and thus eliminate the risk of miscarriage due to amniocentesis or choriocentesis. It would also enable national access to this NIPD test for a wide range of rare diseases.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Herault
-
Montpellier, Herault, France, 34295
- INSERM-Hospital,
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- older than 18 years old
- pregnant woman between 9 and 34 weeks of gestation
- Couple undergoing prenatal diagnosis for a monogenic disease caused by point mutation(s)
- Written informed consent was obtained for the study
- Prenatal diagnosis has been programmed for the current pregnancy during which maternal blood is collected
- Couple molecular diagnosis results for a monogenic disease caused by point mutation(s) MUST BE AVAILABLE.
Exclusion criteria:
- Couple Genomic DNA are unavailable
- Subjects at risk of transmitting the family disease, but not wishing to know their molecular status
- Individuals under guardianship by court order
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Expectant couple at risk of transmitting a monogenic disease.
Expectant couple (pregnant woman from 9 weeks of gestation and spouse) at risk of transmitting a monogenic disease among the genes included in the trusight one expanded sequencing kit (Illumina).
|
15 pregnant women and their spouses Search for the familial mutation on isolated circulating fetal trophoblastic cells from maternal blood
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concordance rate between cell-based genetic non invasive prenatal test and gold standard prenatal test (choriocentesis or amniocentesis).
Time Frame: at 36 month
|
Analysis of the concordance of the prenatal results obtained by our new NIPD (Non-Invasive Prenatal Diagnosis) approach and those blindly obtained during the gold-standard prenatal genetic test will be carried out for each pregnant woman participating in the study.
|
at 36 month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Non Invasive Prenatal Diagnostic test failure rate.
Time Frame: at 36 month
|
Count of the women enrolled for whom NIPD test will be inconclusive (because of insufficient circulating fetal cells isolation or allele drop out making accurate genotyping impossible).
|
at 36 month
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Claire Guissart, PhD-PharmD, molecular genetics
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
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
Other Study ID Numbers
- RECHMPL18_0281
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.
Clinical Trials on Monogenic Diseases
-
Kunling ShenShengjing Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of... and other collaboratorsRecruiting
-
ApteeusEnrolling by invitationMonogenic DisordersFrance
-
Chinese Academy of Medical Sciences, Fuwai HospitalUnknown
-
Assistance Publique - Hôpitaux de ParisNot yet recruiting
-
University Hospital, BordeauxNot yet recruiting
-
Children's Hospital of Fudan UniversityRecruitingSystemic Lupus Erythematosus | Monogenic LupusChina
-
University Hospital, BordeauxNot yet recruitingMonogenic Obesity | Non Syndromic ObesityFrance
-
University of ChicagoCompleted
-
Joslin Diabetes CenterEnrolling by invitationType 1 Diabetes | Monogenic DiabetesUnited States
-
Assistance Publique - Hôpitaux de ParisCompletedNon Autoimmune Monogenic Diabetes
Clinical Trials on Non invasive prenatal diagnosis
-
University Hospital, MontpellierCompleted
-
University Hospital, MontpellierAgence de La BiomédecineActive, not recruitingFragile X Syndrome | Huntington Disease | Myotonic Dystrophy 1France
-
Assistance Publique - Hôpitaux de ParisInstitut National de la Santé Et de la Recherche Médicale, France; University... and other collaboratorsActive, not recruiting
-
Natera, Inc.CompletedSex Chromosome Aberrations | Chromosome 13 Aneuploidy | Chromosome 18 Aneuploidy | Chromosome 21 Aneuploidy | Other MicrodeletionsUnited States
-
Assistance Publique - Hôpitaux de ParisCompleted
-
University Hospital, CaenTerminated
-
Obstetrix Medical GroupCompleted
-
CHU de Quebec-Universite LavalUniversity of British Columbia; McGill University; Canadian Institutes of Health... and other collaboratorsActive, not recruitingAneuploidy | Prenatal DisorderCanada
-
University Hospital, AngersRecruitingEssential Thrombocythemia | Myeloproliferative Disorder | Primary Myelofibrosis, Prefibrotic Stage | Primary Myelofibrosis, Fibrotic StageFrance
-
Menarini Biomarkers SingaporeRecruitingPregnancy Related | Genetic Disease | Prenatal ScreeningItaly