Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Brief Title

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Official Title

Genetic Study of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Brief Summary

      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.
    

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.
    


Study Type

Observational


Primary Outcome

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


Condition

Cardiomyopathy



Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

351

Start Date

September 2006

Completion Date

March 2013

Primary Completion Date

March 2013

Eligibility 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
      

Gender

All

Ages

10 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Philippe Charron, MD, PhD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT00999947

Organization ID

P051067


Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris


Study Sponsor

Philippe Charron, MD, PhD, Principal Investigator, Pitié-Salpêtrière Hospital


Verification Date

October 2012