Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (DVDA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00999947
First received: September 29, 2009
Last updated: November 21, 2013
Last verified: October 2012
  Purpose

The purpose of this trial is to study the genetic and phenotypic aspects of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), and determine the impact of genetic testing in clinical practice.


Condition
Cardiomyopathy
Arrhythmogenic Right Ventricular Dysplasia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genetic Study of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Determine the genetic origin in patients with ARVD/C whatever the familial context [ Time Frame: at inclusion ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood sample


Enrollment: 351
Study Start Date: September 2006
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC), is an inherited myocardial disease that predominantly affects the right ventricle (RV) and the estimated prevalence in the general population ranges from 1 to 5 in 1000. It is characterized histopathologically by fibro-fatty myocardial replacement and clinically by ventricular arrhythmia that may lead to sudden death, especially in young people and athletes. Clinical diagnosis is based on diagnostic criteria proposed by the International Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (Task Force 1994), but is often difficult due to a broad spectrum of clinical features and a lond period of concealed cardiac expression, with delayed diagnosis.

ARVC/D is familial in 30 to 50% and is typically transmitted as an autosomal dominant trait with variable penetrance. In the past years, the identification of causative mutations in plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2) has fostered the view that ARVC/D is a disorder of the desmosome and provided new insight into its pathogenesis.

The major recent advance in the molecular genetics of ARVD/C might lead to important clinical impact through early and correct diagnosis in patients and relatives, and through potential genotype-phenotype correlations. This key-issue requires first to clarify the optimal molecular strategy, and its efficiency. Such a systematic, detailed and comprehensive mutation screening study is not available until now.

Aim:

Study the genetic and phenotypic aspects of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), and determine the impact of genetic testing in clinical practice.

Methods:

The study was approved by the Pitié-Salpétriêre Hospital ethical committee (CPPRB) and written informed consent was obtained from all participating individuals, recruited in France.

A cohort of 100 unrelated patients with ARVD/C will be recruited. Clinical evaluation will include clinical history, family history, blood sample for DNA analysis 12-lead ECG, signal-average ECG, 24-hour ambulatory ECG, transthoracic echocardiography, MRI and/or radionuclide scintigraphy, and contrast angiography when possible. A clinical diagnosis of ARVD/C is made according to the established European Society of Cardiology / International Society and Federation of Cardiology Task Force major and minor criteria (Task Force 1994).

All available relatives will be proposed for enrollment in the study with blood sample for DNA analysis and non invasive cardiac examination, including 12-lead ECG, signal-average ECG, and transthoracic echocardiography.

Mutational analysis of the five genes encoding desmosomal genes will be performed in all index cases (in plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, desmocollin-2). When mutations will be identified, available relatives will be analysed. In index cases without desmosomal mutation, additional analyses will be performed according to a candidate gene strategy and, when possible, through a genome wide approach and linkage analyses.

Expected results:

Determine the genetic origin in patients with ARVD/C whatever the familial context.

Determine a molecular strategy for routine genetic testing. Determine the impact of genetic testing as a diagnostic test in patients and relatives.

Determine the impact of genetics as a prognostic tool, through phenotype-genotype analyses.

Determine the natural evolution of the disease in relatives, and the penetrance.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Unrelated patients with ARVD/C. A clinical diagnosis of ARVD/C is made according to the established European Society of Cardiology / International Society and Federation of Cardiology Task Force major and minor criteria (Task Force 1994)

+ All available relatives will be proposed for enrollement in the study

Criteria

Inclusion Criteria:

  • Patient with DVDA diagnostic confirmed
  • Acceptance even follow-up
  • Informed consent

Exclusion Criteria:

  • Impossible to understand the notice information about study
  • Not affiliated with social protection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999947

Locations
France
Pitié-Salpêtrière Hospital
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Philippe Charron, MD, PhD Hôpital de la Salpétrière
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00999947     History of Changes
Other Study ID Numbers: P051067
Study First Received: September 29, 2009
Last Updated: November 21, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
genetics
mutation screening
phenotype-genotype analysis
desmosomal genes

Additional relevant MeSH terms:
Cardiomyopathies
Arrhythmogenic Right Ventricular Dysplasia
Heart Diseases
Cardiovascular Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Congenital Abnormalities

ClinicalTrials.gov processed this record on October 16, 2014