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ANDDI-PRENATOME - Feasibility Study for a " Fast " Pangenomic High Throughput Sequencing Analysis in Prenatal Diagnosis (AnddiPrenatome)

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ClinicalTrials.gov Identifier: NCT03964441
Recruitment Status : Recruiting
First Posted : May 28, 2019
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire Dijon

Brief Summary:

Prenatal diagnosis of genetic diseases is a real medical challenge. The discovery of antenatal abnormalities on ultrasound is frequent (5 to 10% of pregnancies), and when an abnormalities is seen on ultrasound, it raises the possibility of an underlying developmental anomaly. Currently, in France, when abnormalities are discovered with an ultrasound scan, the etiological diagnosis is based on additional imaging tests (cerebral MRI, 3D bone tomography, fetal CT, fetal CT) or diagnostic tests such as invasive chorionic villus sampling, amniocentesis or fetal blood for infectious, metabolic, immunological and genetic investigations (standard karyotype, FISH (fluorescence in situ hybridization) for the rapid detection of aneuploidy, Chromosome Analysis on DNA Chip (ACPA or CGH-array) and possible sequencing of targeted genes when they are available within a time frame compatible with pregnancy). NIPT (Non-invasive prenatal testing) on cell free fetal DNA circulating in maternal blood has more limited indications, allowing, from an early stage of pregnancy, the determination of fetal sex and fetal rhesus factor and the search for aneuploidy.

However, establishing an etiological diagnosis during pregnancy has many benefits for the parents: clarifying the cause, obtaining a more precise prognosis to determine future management and outcome of the pregnancy, and establishing the risks of recurrence.

Over the past decade, medical genetics has undergone a real technological revolution, leading to the development of high throughput genome-wide, exome (ES) and genome (GS) sequencing. However, few countries have currently embarked on ES/GS in prenatal care, due to the constraints of time and the difficulty of interpreting genomic data when the clinical data is limited to antenatal imaging data.

In 2016, France launched the France Medicine Genomics 2025 Plan (PFMG2025) to deploy GS, particularly in the diagnosis of rare diseases. It is thus becoming essential to define the modalities of prescription of this testing, in particular during prenatal diagnosis. In parallel, from the first publications, the applications of genomic analysis on circulating fetal DNA seem to be able to extend to genome sequencing for research of SNVs responsible for developmental diseases.

The AnDDI-rares health network therefore proposes this ANDDI-PRENATOME pilot project to study the feasibility of a "rapid" analysis of ES in prenatal diagnosis from 61 fetuses with ultrasound abnormalities, as a first step before considering future cost-effectiveness (PRME) or care system performance (PREPS) studies in conjunction with the PFMG2025.


Condition or disease Intervention/treatment
Prenatal Genome-wide High Throughput Sequencing Biological: Invasive fetal sampling, blood sampling of mother and father Biological: blood sampling from the mother to recover the circulating cell free fetal DNA

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Study Type : Observational
Estimated Enrollment : 61 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ANDDI-PRENATOME - Feasibility Study for a " Fast " Pangenomic High Throughput Sequencing Analysis in Prenatal Diagnosis
Actual Study Start Date : June 20, 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prenatal Testing

Group/Cohort Intervention/treatment
control
fetus with at least 2 ultrasound abnormalities and both parents
Biological: Invasive fetal sampling, blood sampling of mother and father
to perform an exome sequencing analysis in trio

comparison
fetus with at least 2 ultrasound abnormalities with ES diagnosis on invasive fetal sampling
Biological: Invasive fetal sampling, blood sampling of mother and father
to perform an exome sequencing analysis in trio

Biological: blood sampling from the mother to recover the circulating cell free fetal DNA
to perform a sequencing analysis of the genome of circulating free fetal DNA




Primary Outcome Measures :
  1. Time required to return ES results to patients and their families in a context prenatal diagnosis [ Time Frame: Through study completion, an average of 12 months ]
  2. number of discrepancies between ES and WGS [ Time Frame: Through study completion, an average of 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women with antenatal discovery of at least two obstetrical ultrasound abnormalities
Criteria

Inclusion Criteria:

  • Pregnant women with antenatal discovery of at least two obstetric ultrasound abnormalities (2 major malformations, or 1 major malformation and 1 minor malformation, or 1 isolated malformation with a high probability of a genetic condition) : who undergo invasive antenatal sampling for CGH-array diagnosis ; who has already had an invasive antenatal sampling for the diagnosis of CGH-array and for which the fetal CGH-array has been found to be normal (sufficient fetal DNA or amniotic fluid should be available to allow exome sequencing to be performed without further amniotic fluid puncture).
  • Pregnant woman and father aged 18 years or more
  • Written consent provided by the pregnant woman and the father of the fetus
  • Possibility of sufficient fetal specimen (amniotic fluid or fetal blood) to collect an additional sample for the pilot project
  • Possibility of sampling the pregnant woman and the father of the foetus (peripheral blood)
  • Pregnant woman and father of the fetus able to understand the study

Exclusion Criteria:

  • Diagnostic hypothesis considered highly probable that can be confirmed by an available molecular or cytogenetic test with a lower cost than ES (e. g. 22q11 microdeletion) or high suspicion of fetal infection (e. g. toxoplamosis seroconversion)
  • Refusal of pregnant woman or father of fetus to participate in the study
  • Pregnancy earlier than 15 weeks of amenorrhea or later than 34 weeks of amenorrhea
  • Pregnant woman and father of the foetus not covered by the national health insurance system
  • Pregnant woman and/or father of the fetus under partial judicial protection

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): NCT03964441


Contacts
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Contact: Christel THAUVIN 03.80.29.53.13 ext +33 christel.thauvin@chu-dijon.fr

Locations
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France
CHU Dijon Bourgogne Recruiting
Dijon, France, 21079
Contact: Christel THAUVIN    03.80.29.53.13 ext +33    christel.thauvin@chu-dijon.fr   
Sponsors and Collaborators
Centre Hospitalier Universitaire Dijon
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Responsible Party: Centre Hospitalier Universitaire Dijon
ClinicalTrials.gov Identifier: NCT03964441    
Other Study ID Numbers: THAUVIN AnDDI rares 2018
First Posted: May 28, 2019    Key Record Dates
Last Update Posted: July 1, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No