Genetics of Ventriculo-arterial Discordance

Heart Defects, Congenital Clinical Trial

— PreciPed  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05330338
• Other study ID #: RC21_0555
• Status: Recruiting
• Phase: N/A
• Start date: September 7, 2022
• Est. completion date: August 1, 2043

Study information

• Verified date: August 2023
• Source: Nantes University Hospital
• Contact: Alban Baruteau
• Phone: 02 40 08 77 42
• Email: albanelouen.baruteau[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: August 1, 2043
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Minute to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Congenital Abnormalities
• Heart Defects, Congenital

Intervention

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

Locations

Country	Name	City	State
France	CHU Angers	Angers	Maine-et-Loire
France	CHU Bordeaux	Bordeaux	Gironde
France	CHU de Caen	Caen	Normandie
France	Groupe Hospitalier St Joseph - Hôpital Marie Lannelongue	Le Plessis-Robinson	Hauts-de-Seine
France	CHU de Lille	Lille	Hauts-de-France
France	Intercard Lille	Lille	Nord
France	CHU Lyon	Lyon	Rhône
France	CHU Marseille	Marseille	Bouches-du-Rhône
France	CHU Nancy	Nancy	Meurthe-et-Moselle
France	CHU Nantes	Nantes	Loire-Atlantique
France	Hôpital Européen Georges Pompidou	Paris
France	CHU Rennes	Rennes	Bretagne
France	CHU Rouen	Rouen	Seine-Maritime
France	Hôpital Nord Laennec	Saint-Herblain	Loire-Atlantique
France	CHU Toulouse	Toulouse	Haute-Garonne
France	CHU Tours	Tours	Val De Loire

Sponsors (4)

Lead Sponsor	Collaborator
Nantes University Hospital	CIC-FEA, CIC 1413, CHU Nantes, Clinique des Données, CIC 1413, CHU Nantes, Inserm UMR1087, CNRS UMR6291

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Evolution of diagnostic performance for congenital heart disease in relatives of the index case with ventriculo-arterial discordance following the introduction of parental screening.	24 months
Secondary	Identification new familial forms of ventriculo-arterial discordance.	Identification of genotype/phenotype relationships by studying associations between clinical features and identified genetic variants.	24 months
Secondary	Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory.	Detection of epigenetic modifications.	24 months
Secondary	Identification allelic variants associated with prognosis and/or response to treatment, with the aim of eventually developing a precision medicine programme in paediatric cardiology	Identification of genotype/phenotype relationships in relation to prognosis and/or response to treatment	20 years
Secondary	Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents	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)	20 years
Secondary	Assessing the quality of life of patients with ventriculo-arterial discordance as well as their parents	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)	20 years