Genetics of Ventriculo-arterial Discordance
- Conditions
- Heart Defects, Congenital
- Registration Number
- NCT05330338
- Lead Sponsor
- Nantes University Hospital
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 600
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method 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. 24 months Identification of de novo genetic variants using a whole genome sequencing (WGS) approach in the context of familial trios analysis
- Secondary Outcome Measures
Name Time Method Identification new familial forms of ventriculo-arterial discordance. 24 months Identification of genotype/phenotype relationships by studying associations between clinical features and identified genetic variants.
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 Evolution of diagnostic performance for congenital heart disease in relatives of the index case with ventriculo-arterial discordance following the introduction of parental screening.
Identification allelic variants associated with prognosis and/or response to treatment, with the aim of eventually developing a precision medicine programme in paediatric cardiology 20 years Identification of genotype/phenotype relationships in relation to prognosis and/or response to treatment
Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory. 24 months Detection of epigenetic modifications.
Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents 20 years To document quality of life longitudinally in this patient population using The Short Form (36) Health Survey (scale from 1 to 6 ; 6 being the worst outcome)
Trial Locations
- Locations (16)
CHU Marseille
馃嚝馃嚪Marseille, Bouches-du-Rh么ne, France
CHU Rennes
馃嚝馃嚪Rennes, Bretagne, France
CHU Bordeaux
馃嚝馃嚪Bordeaux, Gironde, France
CHU Toulouse
馃嚝馃嚪Toulouse, Haute-Garonne, France
CHU de Lille
馃嚝馃嚪Lille, Hauts-de-France, France
CHU Nancy
馃嚝馃嚪Nancy, Meurthe-et-Moselle, France
Groupe Hospitalier St Joseph - H么pital Marie Lannelongue
馃嚝馃嚪Le Plessis-Robinson, Hauts-de-Seine, France
CHU Nantes
馃嚝馃嚪Nantes, Loire-Atlantique, France
H么pital Nord Laennec
馃嚝馃嚪Saint-Herblain, Loire-Atlantique, France
CHU Angers
馃嚝馃嚪Angers, Maine-et-Loire, France
Intercard Lille
馃嚝馃嚪Lille, Nord, France
CHU de Caen
馃嚝馃嚪Caen, Normandie, France
CHU Lyon
馃嚝馃嚪Lyon, Rh么ne, France
CHU Rouen
馃嚝馃嚪Rouen, Seine-Maritime, France
CHU Tours
馃嚝馃嚪Tours, Val de Loire, France
H么pital Europ茅en Georges Pompidou
馃嚝馃嚪Paris, France