Clinical trial NCT05330338: Genetics of Ventriculo-arterial Discordance
Official title: Genetics of Ventriculo-arterial Discordance: Towards a PRECIsion Medicine in PEDiatric Cardiology
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Inserm UMR1087, CNRS UMR6291
name: Clinique des Données, CIC 1413, CHU Nantes
name: CIC-FEA, CIC 1413, CHU Nantes
First posted: 2022-04-15
Enrollment: 600
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 600 participants (150 single cases and 150 trio families)
Primary purpose: OTHER

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: 22 years. Recruitment period: 24 months. Follow-up

time per patients : 20 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 20 year follow-up:

* Retrieval of data from the index case
* Completion of the quality of life questionnaire


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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.
timeFrame: 24 months
Secondary outcomes:
measure: 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.
timeFrame: 24 months
measure: Identification new familial forms of ventriculo-arterial discordance.
timeFrame: 24 months
measure: Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory.
timeFrame: 24 months
measure: Identification allelic variants associated with prognosis and/or response to treatment, with the aim of eventually developing a precision medicine programme in paediatric cardiology
timeFrame: 20 years
measure: Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents
timeFrame: 20 years
measure: Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents
timeFrame: 20 years
Other outcomes:
Locations:
city: Marseille
country: France
facility: CHU Marseille
state: Bouches-du-Rhône
city: Rennes
country: France
facility: CHU Rennes
state: Bretagne
city: Bordeaux
country: France
facility: CHU Bordeaux
state: Gironde
city: Toulouse
country: France
facility: CHU Toulouse
state: Haute-Garonne
city: Lille
country: France
facility: CHU de Lille
state: Hauts-de-France
city: Le Plessis-Robinson
country: France
facility: Groupe Hospitalier St Joseph - Hôpital Marie Lannelongue
state: Hauts-de-Seine
city: Nantes
country: France
facility: CHU Nantes
state: Loire-Atlantique
city: Saint-Herblain
country: France
facility: Hôpital Nord Laennec
state: Loire-Atlantique
city: Angers
country: France
facility: CHU Angers
state: Maine-et-Loire
city: Nancy
country: France
facility: CHU Nancy
state: Meurthe-et-Moselle
city: Lille
country: France
facility: Intercard Lille
state: Nord
city: Caen
country: France
facility: CHU de Caen
state: Normandie
city: Lyon
country: France
facility: CHU Lyon
state: Rhône
city: Rouen
country: France
facility: CHU Rouen
state: Seine-Maritime
city: Tours
country: France
facility: CHU Tours
state: Val de Loire
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
Study officials:
References: