Genetics of Ventriculo-arterial Discordance (PreciPed)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Defects, Congenital
• Intervention / Treatment: Biological: Genetic analyses: whole genome sequencing

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13000
      • CHU Marseille
  • Brittany Region
    • Rennes, Brittany Region, France, 35000
      • Chu Rennes
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • CHU Bordeaux
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31000
      • CHU Toulouse
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59000
      • CHU de Lille
  • Hauts-de-Seine
    • Le Plessis-Robinson, Hauts-de-Seine, France, 92350
      • Groupe Hospitalier St Joseph - Hôpital Marie Lannelongue
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • CHU Nantes
    • Saint-Herblain, Loire-Atlantique, France, 44093
      • Hopital Nord Laennec
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49000
      • CHU Angers
  • Meurthe-et-Moselle
    • Nancy, Meurthe-et-Moselle, France, 54000
      • CHU Nancy
  • Nord
    • Lille, Nord, France, 59000
      • Intercard Lille
  • Normandy
    • Caen, Normandy, France, 14000
      • CHU de Caen
  • Paris
    • Paris, Paris, France, 75000
      • Hôpital Européen Georges Pompidou
  • Rhône
    • Lyon, Rhône, France, 69000
      • CHU Lyon
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76000
      • CHU Rouen
  • Val de Loire
    • Tours, Val de Loire, France, 37000
      • CHU Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Identification epigenetic modifications by analysis of the epigenome of sporadic forms when genome sequencing is not contributory.	Detection of epigenetic modifications.	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	Identification of genotype/phenotype relationships in relation to prognosis and/or response to treatment	2 years
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)	2 years
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)	2 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Inserm UMR1087, CNRS UMR6291; Clinique des Données, CIC 1413, CHU Nantes; CIC-FEA, CIC 1413, CHU Nantes

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2022
• Primary Completion (Actual): June 24, 2025
• Study Completion (Estimated): June 24, 2027

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Genetic; Whole genome sequencing; Congenital heart disease; Ventriculo-arterial discordance; Transposition of the great arteries; Transposition congenitally corrected of the great arteries
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Congenitally Corrected Transposition of the Great Arteries; Heart Defects, Congenital; Transposition of Great Vessels
• Other Study ID Numbers: RC21_0555

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No