Identification of Genetic Basis of Atrioventricular Conduction Defects: From Congenital Forms to Degenerative Forms

Identification of genes involved in congenital atrioventricular block and progressive Cardiac Conduction Disease.

Study Overview

• Status: Recruiting
• Conditions: Congenital Complete Heart Block; Cardiac Conduction Defect Progressive
• Intervention / Treatment: Genetic: genetic blood analysis

Detailed Description

Atrioventricular blocks are a heterogenous group of diseases involving children with congenital atrioventricular block (CAB) and more frequently elderly patients affected by progressive Cardiac Conduction Disease (PCCD).

The aim of the study is to uncover the genetic model, likely more complex than previously appreciated, and characterize the gene expression remodelling leading to high degree of conduction defect.

The recent technological developments in genomics coupled to the availability of large and highly characterized biobanks of patients have now set the stage:

1. To identify rare genetic variants/new genes contributing to CAB and PCCD by exome sequencing on familial form suspected to impact strongly the phenotype
2. To identify common genetic variants modulating the risk of developing (severe) PCCD by GWAS
3. To estimate the prevalence and relevance of genes uncovered by TASK#1, #2 in large patient sets (PCCD and CAB) by NGS.

• Study Type: Observational
• Enrollment (Anticipated): 2600

Contacts and Locations

• Study Contact: Name: vincent PROBST, MD-PHD; Email: vincent.probst@chu-nantes.fr

Study Locations

• France
  • Nantes, France
    • Recruiting
    • CHU Nantes
    • Contact: VINCENT PROBST, MD-PHD
  • Rennes, France
    • Recruiting
    • CHU Rennes
    • Contact: PHILIPPE MABO, MD-PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients of both sex with Atrioventricular Conduction Defects and relatives examined during familial screening

Description

Congenital atrioventricular block inclusion criteria:

• Patients with idiopathic congenital atrioventricular block diagnosed before the age of 15 years.
• Non-immune congenital atrioventricular block documented by a maternal serology (negative for anti-nuclear antibodies or anti Ro-SSA antibodies and anti La-SSB antibodies)
• Written consent to participate to the study and written consent of both parents.
• Parents of children with idiopathic congenital atrioventricular block.

Congenital atrioventricular block exclusion criteria

• Positive maternal serology
• Patients or parents who are unable to sign or who refuse to sign an informed consent

Progressive Cardiac Conduction Disease inclusion criteria

• Patients with isolated cardiac conduction disorder with a normal morphology of the heart confirmed by echocardiography.
• Relatives of patients with isolated cardiac conduction disorder
• Written consent to participate to the study

Progressive Cardiac Conduction Disease exclusion criteria

• Patients with cardiac conduction disorder associated with a structural cardiopathy or due to an identified cause
• Patients who are unable to sign or who refuse to sign an informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with congenital atrioventricular block; Patient with congenital atrioventricular block	Genetic: genetic blood analysis; patients will undergo a blood sample (15 ml) to analyse their genetic profile
relatives with congenital atrioventricular block; Normal relatives of patients with congenital atrioventricular block	Genetic: genetic blood analysis; patients will undergo a blood sample (15 ml) to analyse their genetic profile
Patients with progressive Cardiac Conduction Disease; Patients with progressive Cardiac Conduction Disease,	Genetic: genetic blood analysis; patients will undergo a blood sample (15 ml) to analyse their genetic profile
relatives with progressive Cardiac Conduction disesae; Normal relatives of patients with progressive Cardiac Conduction Disease	Genetic: genetic blood analysis; patients will undergo a blood sample (15 ml) to analyse their genetic profile

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of genetic variations responsible of Atrioventricular Conduction Defects	inclusion

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: vincent PROBST, MD-PHD, CHU de Nantes

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: August 24, 2016
• First Submitted That Met QC Criteria: August 24, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): September 9, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: genetic; congenital atrioventricular block; progressive Cardiac Conduction Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Block; Cardiac Conduction System Disease
• Other Study ID Numbers: PROG/11/33

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