Canadian National ARVC Registry

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Population Health Research Institute
Medtronic
Boston Scientific Corporation
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01804699
First received: March 1, 2013
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition that may cause life threatening irregular heart rhythms that often manifest as unexpected cardiac arrest or sudden death in early adulthood. The condition is difficult to diagnose and often is not noticed until a family member suffers a cardiac arrest or death.

The Canadian National ARVC registry will collect data from Inherited Heart Rhythm Clinics across Canada.

STUDY OBJECTIVES:

Primary:

  1. To determine the natural history of ARVC (short/intermediate term), including risk of symptomatic arrhythmias and sudden death, for patients with the phenotype and those gene positive patients without phenotype evidence of disease.
  2. To understand risk factors for sudden death/appropriate ICD use in ARVC, including test characteristics/performance and their relationship to outcomes (ECG, Holter, signal averaged ECG, loop recorders, imaging, voltage mapping, T wave alternans, cardiac biopsy and biomarkers).
  3. To establish a phenotype genotype correlation, including comparison of patients with disease causing mutations, variants of unknown significance (VUS) and Task Force Criteria (TFC) positive, gene negative patients

Condition
Arrhythmogenic Right Ventricular Cardiomyopathy

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Family-Based
Time Perspective: Prospective
Target Follow-Up Duration: 3 Years
Official Title: Canadian National Arrhythmogenic Right Ventricular Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Natural History of ARVC [ Time Frame: Three years ] [ Designated as safety issue: No ]
    To determine the natural history of ARVC (short/intermediate term), including risk of symptomatic arrhythmias and sudden death, for patients with the phenotype and those gene positive patients without phenotype evidence of disease.


Secondary Outcome Measures:
  • Risk Factors and Sudden Death [ Time Frame: Three Years ] [ Designated as safety issue: Yes ]
    To understand risk factors for sudden death/appropriate ICD use in ARVC, including test characteristics/performance and their relationship to outcomes (ECG, Holter, signal averaged ECG, loop recorders, imaging, voltage mapping, T wave alternans, cardiac biopsy and biomarkers).


Other Outcome Measures:
  • Establishing a phenotype genotype correlation [ Time Frame: Three Years ] [ Designated as safety issue: No ]
    To establish a phenotype genotype correlation, including comparison of patients with disease causing mutations, variants of unknown significance (VUS) and Task Force Criteria (TFC) positive, gene negative patients


Biospecimen Retention:   Samples With DNA

If the participant consents to the biobanking arm of the study an additional blood sample (Please see the ARVC Lab Manual for details) will be collected at baseline and stored for subsequent analysis. These analyses may include measurement of serum Troponin T, NT-pro-BNP, C-reactive protein and other biomarkers to determine their association with the progression of disease; both in terms of cardiac structure (i.e. change in right ventricular volume) and electrical substrate (i.e. number of ICD shocks) over time.


Estimated Enrollment: 1500
Study Start Date: January 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Proband
Probands - Participants diagnosed with ARVC according to the 2010 Task Force Criteria
Family
First Degree Family member (blood related mother, father, sister, brother, child) of the proband

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Patients will be identified from centers that form the Canadian Genetics Heart Rhythm (CGHR) Network of Inherited Heart Rhythm Clinics across Canada 25 (http://www.heartrhythmresearch.ca/).

Criteria

IInclusion Requirements:

  1. 2010 Revised Task Force Criteria positive patients (please refer to Appendix 3.0)
  2. 2010 Revised Task Force Criteria borderline patients
  3. Disease causing ARVC pathogenic mutation* carriers with no TFC criteria for ARVC
  4. Variants of unknown significance carriers with ≥1 minor TFC criterion
  5. Age ≥ 2 years
  6. First-degree relatives of 2010 Revised Task Force Criteria positive or borderline patients
  7. Able and willing to provide informed consent, or has a parent/guardian able and willing to provide informed consent and/or able to sign an assent form

    • A pathogenic mutation is a DNA alteration associated with ARVC/D that alters or is expected to alter the encoded protein in a significant way, is unobserved or rare in a large non-ARVC/D control population, and either alters or is predicted to alter the structure or function of the protein (by computational (in silico) predictions and/or functional validation in a biological model system) or has demonstrated linkage to the disease phenotype in a conclusive pedigree 4. Mutation carriers by definition have a single major Task Force criterion.

EXCLUSION CRITERIA:

Exclusion Requirements:

  1. Known condition that mimics ARVC - sarcoidosis (biopsy proven or with lung involvement), familial dilated cardiomyopathy not compatible with an ARVC variant, hypertrophic cardiomyopathy
  2. Known inherited condition that predisposes to sudden death - Long or Short QT Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia and Brugada Syndrome
  3. Age < 2 years
  4. Life expectancy less than 1 year
  5. Unable and/or unwilling to provide informed consent
  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: NCT01804699

Locations
Canada, Alberta
Foothills Hospital
Calgary, Alberta, Canada
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada
Canada, Newfoundland and Labrador
Health Sciences Centre, Newfounland
Saint John's, Newfoundland and Labrador, Canada
Canada, Nova Scotia
QEII Health Siences Centre
Halifax, Nova Scotia, Canada
Canada, Ontario
Hamilton Health Sciences Centre
Hamilton, Ontario, Canada
University of Western Ontario
London, Ontario, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
Ottawa Heart Institute
Ottawa, Ontario, Canada
Sunnybrook Hospital
Toronto, Ontario, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Sick Children's Hospital
Toronto, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada
Canada
Quebec Heart Institute Laval Hospital
Quebec, Canada
Sponsors and Collaborators
University of British Columbia
Population Health Research Institute
Medtronic
Boston Scientific Corporation
Heart and Stroke Foundation of Ontario
Investigators
Principal Investigator: Andrew D Krahn, MD University of British Columbia, Dept of Medicine, Head of Cardiology
  More Information

No publications provided

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01804699     History of Changes
Other Study ID Numbers: H12-03189
Study First Received: March 1, 2013
Last Updated: July 15, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
ARVC, Cardiomyopathy

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 September 30, 2014