PreciPed: Genetics of Ventriculo-arterial Discordance

Sponsor

Nantes University Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05330338

Collaborator

Inserm UMR1087, CNRS UMR6291 (Other), Clinique des Données, CIC 1413, CHU Nantes (Other), CIC-FEA, CIC 1413, CHU Nantes (Other)

600

Enrollment

Locations

Arm

240

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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 : 300 index cases: 150 single index cases and 150 trio families

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

Condition or Disease	Intervention/Treatment	Phase
Heart Defects, Congenital	Biological: Genetic analyses: whole genome sequencing	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

600 participants (150 single cases and 150 trio families)600 participants (150 single cases and 150 trio families)

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Genetics of Ventriculo-arterial Discordance: Towards a PRECIsion Medicine in PEDiatric Cardiology

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

May 1, 2042

Arms and Interventions

Arm	Intervention/Treatment
Other: Congenital heart disease	Biological: Genetic analyses: whole genome sequencing Identification of de novo genetic variants using a whole genome sequencing (WGS) approach in the context of familial trios analysis

Arm

Intervention/Treatment

Other: Congenital heart disease

Biological: Genetic analyses: whole genome sequencing

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

Outcome Measures

Primary Outcome Measures

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

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 new familial forms of ventriculo-arterial discordance. [24 months]
Identification of genotype/phenotype relationships by studying associations between clinical features and identified genetic variants.
Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory. [24 months]
Detection of epigenetic modifications.
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
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 Pediatric Quality of Life InventoryTM (scale from 0 to 4 ; 4 being the worst outcome)

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Minute to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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
Patients under guardianship/curatorship
Patients with State Medical Aid
Refusal of consent by the patient and/or one of the two parents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU Marseille	Marseille	Bouches-du-Rhône	France	13000
2	CHU Rennes	Rennes	Bretagne	France	35000
3	CHU Bordeaux	Bordeaux	Gironde	France	33000
4	CHU Toulouse	Toulouse	Haute-Garonne	France	31000
5	Groupe Hospitalier St Joseph - Hôpital Marie Lannelongue	Le Plessis-Robinson	Hauts-de-Seine	France	92350
6	CHU Grenoble	Grenoble	Isère	France	38000
7	CHU Nantes	Nantes	Loire-Atlantique	France	44000
8	Hôpital Nord Laennec	Saint-Herblain	Loire-Atlantique	France	44093
9	CHU Angers	Angers	Maine-et-Loire	France	49000
10	CHU Nancy	Nancy	Meurthe-et-Moselle	France	54000
11	Intercard Lille	Lille	Nord	France	59000
12	CHU Lyon	Lyon	Rhône	France	69000
13	CHU Rouen	Rouen	Seine-Maritime	France	76000
14	CHU Tours	Tours	Val De Loire	France	37000
15	Hôpital Européen Georges Pompidou	Paris		France	75000