Antenatal Investigation of Fetuses With Complex Congenital Heart Defects Using multiOMICS (CARDIOMICS)

April 9, 2025 updated by: University Hospital, Bordeaux
This study will use multiOMICS study on fetuses with complexe congenital heart defects (CHD) to identify etiological epigenetic factors of these cardiac malformations, related to environmental factors during pregnancy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Congenital heart defects (CHDs) are a very heterogeneous group of heart diseases in terms of embryonic mechanisms, phenotypes and aetiologies. In isolated forms, genetic causes are identified in only 19% of cases, linked to chromosomal abnormalities (8%) or gene variants (11%). Environmental causes such as infection, exposure to toxic substances or ingestion of teratogenic substances may also favour the onset of MCC. Although in the majority of cases the aetiology remains unknown, the discovery of MCC in the ante-natal period almost systematically leads to a genetic aetiological work-up using amniotic fluid for karyotype, Array-CGH and, more recently, exome analysis. With regard to environmental causes, recent data in the literature report a link between environmental exposures (occupational, extra-occupational or medicinal) and congenital anomalies.

Objectives: The low percentage of genetic abnormalities and toxic factors identified as causal in patients with non-syndromic CHD prompts a search for more complex causes such as epigenetic modifications linked to an interaction between genes and environmental factors.

Methods: The multi-omics study approach, using high-throughput sequencing technologies (exome, RNASeq, methylSeq), provides a wealth of information on cellular and/or tissue signaling pathways in response to exposure. Integrated analysis of transcriptomes and methylomes has demonstrated the occurrence of combined defects in gene expression and methylation following toxic exposure. The period of CHD formation during embryonic development prompts us to look for epigenetic modifications during prenatal period, as close as possible to the pathophysiological mechanisms leading to this malformation.

Expected results: the multi-omics analysis applied to fetuses with non-syndromic complex CHD, combined with the characterization of occupational and non-occupational environmental exposures, will enable us to extend the etiological search for these malformations, to identify biomarkers linked to the occurrence and severity of these malformations and gain a better understanding of the pathophysiological mechanisms linked to CHD.

In the longer term, this study will serve as a basis for large-scale studies to enable the development of prevention policies, based on exhaustive, multicenter cohorts. In addition, multi-omics studies could identify gene markers, by exome, transcriptome and/or methylome, which could then be studied in a targeted manner.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • 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 Locations

  • France
      • Bordeaux, France, 33076
      • Nantes, France, 44093
        • Not yet recruiting
        • Chu de Nantes
        • Contact:
          • Marie VINCENT, DR
          • Phone Number: 0240087516

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

Fetuses with congenital heart disease :

  • Pregnant women aged 18 and more
  • Single foetal pregnancy in which the foetus has a complex non-syndromic congenital heart defect, with no identified chromosomal abnormality, gene syndrome or infection.
  • Patient for whom the indication for amniocentesis has been accepted by the CPDPN and accepted by the couple/patient
  • Gestational age between 20 and 28 weeks' gestation.
  • Person affiliated to or benefiting from a social security scheme.
  • Free, informed and express consent (confirmed in writing) (at the latest on the day of inclusion and before any examination required by the research).

Control Population for RNAseq and MéthlySeq

  • Pregnant women aged 18 and more
  • Patient in whom the indication for amniocentesis has been retained by the CPDPN and accepted by the couple/patient, for a non-malformative ultrasound anomaly (hyperechoic bowel, idiopathic hydramnios, increased risk of trisomy 21, agenesis of the OPN, suspected toxoplasmosis/CMV seroconversion), with no chromosomal anomaly, gene syndrome or infection identified.
  • Gestational age between 20 and 28 weeks' gestation.
  • Person affiliated to or benefiting from a social security scheme.
  • Free, informed and express consent (confirmed in writing) (at the latest on the day of inclusion and before any examination required by the research).

Exclusion Criteria:

For both populations (cases and controls) :

  • Female minors,
  • Patients not affiliated to the social security system,
  • Patients who do not understand French,
  • Patients under guardianship
  • Multiple pregnancies, or where the foetus has associated malformations

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: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Congenital Heart Defects population
Genetic: multi-omics genetic analyses included exome

Genetic analysis will be carried out on amniotic fluid from the volume collected as part of the by obstetricians working in the fetal medicine unit. These genetic analyses will include :

  • Study of free RNA circulating in the LA,
  • Methylome study.
  • Trio exome study (parents-fetus).
Placebo Comparator: control population
Genetic: multi-omics genetic analyses

Genetic analysis will be carried out on amniotic fluid from the volume collected as part of the by obstetricians working in the fetal medicine unit; These genetic analyses will include :

  • Study of free RNA circulating in the LA,
  • Methylome study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac malformations biomarkers
Time Frame: Visit 1 : day 0
Identification of biomarkers such as RNA deregulation (mRNA, LncRNA, miRNA, upregulated or deregulated compared to controls), and DNA methylation marks (present or absent, compared to controls) specific to cardiac malformations by transcriptomic and methylomic analysis of amniotic fluid from fetuses with congenital heart disease
Visit 1 : day 0

Collaborators and Investigators

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

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Caroline ROORYCK-THAMBO, PROF, University Hospital, Bordeaux

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)

April 1, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 18, 2024

First Submitted That Met QC Criteria

November 21, 2024

First Posted (Actual)

November 26, 2024

Study Record Updates

Last Update Posted (Actual)

April 10, 2025

Last Update Submitted That Met QC Criteria

April 9, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2024/30

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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