Genetics of Ventriculo-arterial Discordance

NCT05330338 | Active Not Recruiting

• 1 other identifier: RC21_0555
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 16

Brief Summary

Number of centres planned : 16 centres in France Type of study / Study design : Research Involving the Human Person category 2. Multicentric. Prospective Planning of the study : Total duration: 57,5 months. Recruitment period: 33.5 months. Follow-up time per patients : 2 years Expected number of cases : The study will involve a maximum of 900 individuals, from 16 centers in France300 family trios (consisting of 150 index cases and their 2 parents, healthy volunteers, N= 450 individuals) \- In the event of unavailability, refusal, non-compliance with an inclusion or exclusion criterion concerning one of the biological parents, only the index case (patient) will be included in the study without his or her parents. The 300 index cases with ventriculo-arterial discordance will be divided into two groups: 100 double discordance cases and 200 large-vessel transpositions. These group inclusion targets are theoretical. If the proportion of patients available for inclusion turns out to be higher than expected for one of the groups, the targets may be adjusted, while maintaining a maximum of 300 cases included (corresponding to 900 subjects if all trios are complete). Patients and their parents will be informed of the study by their referring cardiologist, and their written consent will be obtained. Translated with DeepL.com (free version) Treatment, procedure, combination of procedures under consideration :

• Blood samples for genetic analyses collected at the inclusion visit for patients and parents in case of trio families Schedule of different visits and examinations : Inclusion visit:
• Collection of demographic, clinical data from the index case and parents
• DNA sampling for genetic research (biocollection) of the index case or family trio
• Completion of the quality of life questionnaire Annual visit with a 2 years follow-up:
• Retrieval of data from the index case
• Completion of the quality of life questionnaire

Conditions

Heart Defects, Congenital

Keywords

Congenital heart disease; Ventriculo-arterial discordance; Transposition of the great arteries; Transposition congenitally corrected of the great arteries; Genetic; Whole genome sequencing

Outcome Measures

Primary Outcomes (1)

• Identification new genes/variants involved in congenital heart disease with transposition congenitally corrected of the great arteries, based on whole genome sequencing of familial trios.

  Identification of de novo genetic variants using a whole genome sequencing (WGS) approach in the context of familial trios analysis

  24 months

Secondary Outcomes (6)

• Evaluation the diagnostic contribution of parental cardiovascular screening in case of ventriculo-arterial discordance (transposition of the great arteries, transposition congenitally corrected of the great arteries) in the index case.

  24 months

• Identification new familial forms of ventriculo-arterial discordance.

  24 months

• Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory.

  24 months

• Identification allelic variants associated with prognosis and/or response to treatment, with the aim of eventually developing a precision medicine programme in paediatric cardiology

  2 years

• Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents

  2 years

Study Arms (1)

Congenital heart disease

OTHER

Biological: Genetic analyses: whole genome sequencing

Interventions

Genetic analyses: whole genome sequencing BIOLOGICAL

Identification of de novo genetic variants using a whole genome sequencing (WGS) approach in the context of familial trios analysis

Congenital heart disease

Eligibility Criteria

• Age: 1 Minute - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with transposition of the great arteries or transposition congenitally corrected of the great arteries with healthy parents and no family history of congenital heart disease (familial trio)
• Or patients with transposition of the great arteries or transposition congenitally corrected of the great arteries with or without a history of congenital heart disease (familial form or sporadic case)
• Affiliated or beneficiaries of a social security scheme or similar
• After obtaining oral consent from patients and/or parents if applicable
• Parents (for family trios) :
• \- Biological parents of the child included in the PRECIPED study

You may not qualify if:

• Patients with transposition of the great arteries or transposition congenitally corrected of the great arteries with hypoplastic ventricle or atrioventricular and/or ventriculoarterial valve atresia
• Patient with an identified malformation syndrome
• Patients under guardianship/curatorship
• Patients with State Medical Aid
• Refusal of consent by the patient and/or one of the two parents

Sponsors & Collaborators

• Nantes University Hospital: lead
• Inserm UMR1087, CNRS UMR6291: collaborator
• Clinique des Données, CIC 1413, CHU Nantes: collaborator
• CIC-FEA, CIC 1413, CHU Nantes: collaborator

Study Sites (16)

CHU Marseille

Marseille, Bouches-du-Rhône, 13000, France

Location

CHU Rennes

Rennes, Brittany Region, 35000, France

Location

CHU Bordeaux

Bordeaux, Gironde, 33000, France

Location

CHU Toulouse

Toulouse, Haute-Garonne, 31000, France

Location

CHU de Lille

Lille, Hauts-de-France, 59000, France

Location

Groupe Hospitalier St Joseph - Hôpital Marie Lannelongue

Le Plessis-Robinson, Hauts-de-Seine, 92350, France

Location

CHU Nantes

Nantes, Loire-Atlantique, 44000, France

Location

Hôpital Nord Laennec

Saint-Herblain, Loire-Atlantique, 44093, France

Location

CHU Angers

Angers, Maine-et-Loire, 49000, France

Location

CHU Nancy

Nancy, Meurthe-et-Moselle, 54000, France

Location

Intercard Lille

Lille, Nord, 59000, France

Location

CHU de Caen

Caen, Normandy, 14000, France

Location

Hôpital Européen Georges Pompidou

Paris, Paris, 75000, France

Location

CHU Lyon

Lyon, Rhône, 69000, France

Location

CHU Rouen

Rouen, Seine-Maritime, 76000, France

Location

CHU Tours

Tours, Val de Loire, 37000, France

Location

MeSH Terms

Conditions

Heart Defects, Congenital; Transposition of Great Vessels; Congenitally Corrected Transposition of the Great Arteries

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 900 participants (300 trio families)

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: April 15, 2022
• Study Start: September 7, 2022
• Primary Completion: June 24, 2025
• Study Completion (Estimated): June 24, 2027
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)