Realization of Sequencing of All Known Human Genes in Case of Detection of Cerebral, Renal or Ophthalmological Fetal Malformations During Pregnancy in Order to Make an Etiological Diagnosis and to Precise the Fetal Prognosis (PRENATEX)

November 10, 2020 updated by: University Hospital, Strasbourg, France

Contribution of the Exome Sequencing in Antenatal Period Behind Ultrasound Features Suggestive of a Rare Genetic Disease

Congenital malformations concern 3% of pregnancies; most of them can be seen during pregnancy. For some malformations, an invasive sample (trophoblast biopsy or amniocentesis) is proposed to search a chromosomal abnormality by the technique of DNA chip. However, some strongly suggestive signs of a genetic (and not chromosomal) pathology have a very low diagnostic rate with this technique. In the absence of an etiological diagnosis, the prognosis for the unborn child is very difficult to assess, as we can't know if the fetal malformation is really isolated or associted to other unseen features as part of a syndromic condition.

For some malformations strongly suggestive of a genetic condition, we propose to realize an exome (i.e. all coding parts of the genome) sequencing of the trio (child and the 2 parents) with a delivery time compatible with the emergency situation of a pregnancy (6 weeks maximum). We will apply bioinformatics filters to analyse only genes known to be involved in the malformation present in the unborn child and thus avoid the identification of variants in unrelated genes. These lists of genes have been previously validated by the Rare Disease Health Sectors and the affiliated diagnostic laboratories. The selected malformations are: 1) anomalies of the central nervous system (microcephaly (<- 2DS) with anomalies of gyration, anomalies of the posterior fossa, anomalies of the midline except agenesis of the corpus callosum), 2) ophthalmological anomalies (microphthalmia, hyperplasia vitreous) and 3) renal abnormalities (large hyperechoic kidneys).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Besançon, France, 25030
        • Not yet recruiting
        • CHU de Besancon
        • Contact:
        • Principal Investigator:
          • Lionel VAN MALDERGEM
        • Sub-Investigator:
          • Juliette PIARD
        • Sub-Investigator:
          • Elise BOUCHER
      • Dijon, France, 21079
        • Not yet recruiting
        • CHU de DIJON
        • Contact:
        • Principal Investigator:
          • Christel THAUVIN
        • Sub-Investigator:
          • Laurence FAIVRE
        • Sub-Investigator:
          • Arthur SORLIN
        • Sub-Investigator:
          • Sébastien MOUTTON
      • Lyon, France
        • Not yet recruiting
        • Hospices Civils de Lyon
        • Contact:
        • Principal Investigator:
          • Audrey PUTOUX
      • Mulhouse, France, 68070
        • Not yet recruiting
        • Groupe Hospitalier Region Mulhouse Et Sud Alsace
        • Contact:
        • Principal Investigator:
          • Emmanuelle GINGLINGER
        • Sub-Investigator:
          • Edgar MONTOYA RAMIREZ
      • Nancy, France, 54042
        • Not yet recruiting
        • CHU de Nancy
        • Contact:
        • Principal Investigator:
          • Laetitia LAMBERT
        • Sub-Investigator:
          • Bruno LEHEUP
      • Paris, France, 75013
        • Not yet recruiting
        • Hopital de la Pitie Salpetriere
        • Contact:
        • Principal Investigator:
          • Delphine HERON
      • Paris, France, 75012
        • Not yet recruiting
        • Hôpital d'Enfants Armand-Trousseau
        • Contact:
        • Principal Investigator:
          • Alexandra AFENJAR
      • Paris, France, 75743
        • Not yet recruiting
        • Hopital Necker Enfants Malades
        • Contact:
        • Principal Investigator:
          • Tania ATTIE-BITACH
      • Reims, France, 51092
        • Not yet recruiting
        • CHU de Reims
        • Contact:
        • Principal Investigator:
          • Martine DOCO-FENZY
        • Sub-Investigator:
          • Céline POIRSIER
      • Rennes, France, 35203
        • Not yet recruiting
        • CHU de Rennes
        • Contact:
        • Principal Investigator:
          • Sylvie ODENT
      • Strasbourg, France, 67098
        • Recruiting
        • Les Hôpitaux Universitaires de Strasbourg
        • Sub-Investigator:
          • Vincent LAUGEL
        • Contact:
        • Principal Investigator:
          • Elise SCHAEFER
        • Sub-Investigator:
          • Hélène DOLLFUS
        • Sub-Investigator:
          • Salima EL CHEHADEH
        • Sub-Investigator:
          • Romain FAVRE
      • Toulouse, France, 31059
        • Not yet recruiting
        • CHU de Toulouse
        • Contact:
        • Principal Investigator:
          • Patrick CALVAS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Father and mother of an unborn child past the age of majority
  • Consent dated and signed by the mother and by the father
  • Father and mother able to understand the objectives and risks of the study
  • For the mother, pregnancy in progress (between 12 and 34 weeks)
  • For the mother, pregnancy with the presence of a malformation on ultrasound, confirmed by a doctor from the multidisciplinary diagnostic prenatal center, entering into the indications retained for this study
  • Clinical validation of the couple's eligibility by an expert for some of selected indications
  • Father and mother affiliated to a social protection health

Exclusion Criteria:

  • Identified genetic or chromosomal abnormality explaining the observed malformation
  • Inability to give informations to the father and / or mother (father or mother in emergency or life-threatening situation)
  • Father and / or mother under the protection of justice
  • Father and / or mother under guardianship or curatorship
  • Nursing woman

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 90 trios (270 subjects: 90 fetus, 90 mothers, 90 fathers)
Genetic: CGH-array and exome sequencing
A blood sample will be used for CGH-array and exome sequencing

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Diagnostic contribution of the exome sequencing in antenatal period in comparison with the chromosomal analysis (CGH-array) realized in current health care
Time Frame: 13 months
Comparison of the number of genetic diagnoses made by exome sequencing and by CGH-array.
13 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effects on pregnancy management and/or postnatal child care due to an etiological diagnosis
Time Frame: 13 months
Percentage of antenatal and/or postnatal fetus/child care modified by the molecular result
13 months
Feasibility study of carrying out exome sequencing in the antenatal period in terms of time to deliver results
Time Frame: 13 months
Time to results from the inclusion of the trio (in days) specifying the time for each step (reception, sequencing, bioinformatics analysis, interpretation) (in days)
13 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Difficulties of interpretation of the exome sequencing in antenatal period
Time Frame: 13 months
Numbers of variants of unknown signification identified by exome sequencing with and without bioinformatic filters (targeted exome)
13 months
Identification of new genes responsible of fetal malformations
Time Frame: 13 months
If the results of CGH-array and targeted exome sequencing are negative, analysis of the entire exome sequencing to find new genes implicated in fetal development
13 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Strasbourg, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 5, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 28, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 7344

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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Conditions

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Drug Interventions

Dietary Supplements

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