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Mayo AVC Registry and Biobank

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ClinicalTrials.gov Identifier: NCT03049254
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : October 3, 2018
Sponsor:
Collaborator:
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Grace Lin, Mayo Clinic

Brief Summary:

Arrhythmogenic ventricular cardiomyopathy (AVC) is a genetic condition which affects the heart and can lead to heart failure and rhythm problems, of which, sudden cardiac arrest or death is the most tragic and dangerous. Diagnosis and screening of blood-relatives is very difficult as the disease process can be subtle, but sufficient enough, so that the first event is sudden death.

The Mayo Clinic AVC Registry is a collaboration between Mayo Clinic, Rochester, USA and Papworth Hospital, Cambridge University Hospitals, Cambridge, UK. The investigators aim to enroll patients with a history of AVC or sudden cardiac death which may be due to AVC, from the US and UK. Family members who are blood-relatives will also be invited, including those who do not have the condition. Data collected include symptoms, ECG, echocardiographic, MRI, Holter, loop recorder, biopsies, exercise stress testing, blood, buccal and saliva samples.

Objectives of the study:

  1. Discover new genes or altered genes (variants) which cause AVC
  2. Identify biomarkers which predict (2a) disease onset, (2b) disease progression, (2c) and the likelihood of arrhythmia (ventricular, supra-ventricular and atrial fibrillation)
  3. Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally using clinical, electrocardiographic and imaging data.
  4. Characterize desmosomal changes in buccal mucosal cells with genotype and validate with gold-standard endomyocardial biopsies

Condition or disease
Arrhythmogenic Right Ventricular Cardiomyopathy Cardiomyopathies Heart Diseases Cardiovascular Diseases Sudden Cardiac Arrest Sudden Cardiac Death Arrhythmogenic Right Ventricular Dysplasia Arrhythmogenic Ventricular Cardiomyopathy Familial Dilated Cardiomyopathy Cardiovascular Abnormalities Sarcoidosis Cardiac Arrhythmia Cardiac Sarcoidosis Myocarditis Inflammatory Cardiomyopathy Ventricular Tachycardia Right Ventricular Outflow Tract Ventricular Tachycardia

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 6000 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: The Mayo Clinic Arrhythmogenic Ventricular Cardiomyopathy Registry and Biobank
Study Start Date : January 2016
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2031


Group/Cohort
Proband
Proband - the person who is the first to present with a diagnosis of AVC
Family members (consultands)
First-degree relatives of probands with AVC (who may be living or deceased) In some circumstances where multiple family members are or may be affected, they may be eligible.



Primary Outcome Measures :
  1. Genotyping [ Time Frame: 3 years ]
    Using family 'trios' discover novel pathogenic variants and characterize them

  2. Correlate genotype with phenotype [ Time Frame: 3-6 years ]
    Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally as per 2010 Task Force Criteria


Secondary Outcome Measures :
  1. Natural history and secular trends of AVC [ Time Frame: 3-6 years ]
    Test blood-based biomarkers (such high-sensitivity CRP, high-sensitivity troponin, NT-proBNP and miRNA) which predict disease onset, disease progression, and the likelihood of arrhythmia.

  2. Natural history and secular trends of AVC [ Time Frame: 3-6 years ]
    Discover ECG-based biomarkers which predict disease onset, disease progression, and the likelihood of arrhythmia.

  3. Natural history and secular trends of AVC [ Time Frame: 3-6 years ]
    Discover MRI-based biomarkers which predict disease onset, disease progression, and the likelihood of arrhythmia.

  4. Cellular and Tissue phenotyping [ Time Frame: 3 years ]
    Characterize desmosomal changes in buccal mucosal cells with endomyocardial biopsies and/or in vivo tissue characterization by cardiac MRI or cardiac CT

  5. Risk factors for sudden death or appropriate ICD discharge [ Time Frame: 5-10 years ]
    Test the performance of biomarkers and risk factors to outcomes of sudden death and/or appropriate ICD therapies by modeling.


Biospecimen Retention:   Samples With DNA
For participants who volunteer and consent to the biobank arm, a baseline blood sample, saliva sample and buccal scrapings will be collected and stored for analyses in the future. The investigators will initially test for exisiting and novel pathogenic variants using next generation whole exome sequencing, which is not approved for clinical diagnosis. However, technologies are rapidly evolving, and samples may be used for whole genome and epigenome analyses. Blood will also be stored for measuring known blood-biomarkers of disease progression (such as high-sensitivity cardiac troponins, natriuretic peptides, high-sensitivity CRP and cytokines). Blood will also be stored for high throughput 'omics (transcriptomics, metabolomics and proteomics) to develop new biomarkers for diagnosis and disease progression.


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

All patients seen at any Mayo Clinic facility or Papworth Hospital.Cambridge University Hospitals, who have AVC will be evaluated via their medical records (retrospective chart review) according to 2010 Task Force Criteria.

Family members who are being screened for AVC are also eligible, as are patients with overlapping conditions (phenocopies such as myocarditis, sarcoidosis, inflammatory cardiomyopathies, outflow tract tachycardias and Brugada pattern, and familial dilated cardiomyopathy).

Patients seen at other institutions who wish to enroll are encourgaed to apply and may be eligible.

For the optional novel genetic variant discovery and biobank phases, patients will be invited to participate and undergo written consent.

Criteria

Inclusion Criteria:

  • Patients with a clinical diagnosis of Arrhythmogenic Ventricular Cardiomyopathy (AVC) or suspected AVC by 2010 Task Force Criteria
  • Patient with arrhythmogenic cardiomyopathy
  • Patients with left dominant arrhythmogenic left ventricular cardiomyopathy
  • Patients with familial dilated cardiomyopathy with a propensity for arrhythmia and/or evidence of cutaneous involvement, that is suggestive of AVC phenotype
  • Patients with phenocopies which may represent early AVC (myocarditis, sarcoidosis, inflammatory cardiomyopathies, outflow tract tachycardias and Brugada pattern)
  • Family members of probands with AVC
  • Patients who have a known pathogenic variant for AVC but do not currently meet 2010 Task Force Criteria (ie genotype positive, phenotype negative)
  • Capacity to provide written consent for genetic and biobank aspects

Exclusion Criteria:

  • Hypertrophic cardiomyopathy
  • Ischemic cardiomyopathy
  • Biopsy proved cardiac amyloidosis
  • Inability or unwillingness to provide a written consent form

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03049254


Contacts
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Contact: Hannah E Frost +1 507 293 2762 Frost.Hannah@mayo.edu
Contact: Anwar A Chahal, MBChB PhD +1 507 255 8795 cpl@mayo.edu

Locations
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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Anwar A Chahal, MBChB MRCP         
Sub-Investigator: Peter A Brady, MD FRCP FHRS         
Sub-Investigator: Anwar A Chahal, MB ChB MRCP         
Sub-Investigator: Virend K Somers, MD PhD         
Principal Investigator: Grace Lin, MD         
United Kingdom
Royal Papworth Hospital NHS Foundation Trust Recruiting
Papworth Everard, Cambridge, United Kingdom, CB23 3RE
Contact: Greg Mellor, MD       CVGenetics@nhs.net   
Contact: Anwar A Chahal, MBChB PhD       CVGenetics@nhs.net   
Principal Investigator: Andrew A Grace, PhD FRCP FHRS         
Sub-Investigator: Anwar A Chahal, MBChB MRCP         
Sub-Investigator: Greg Mellor, MD MRCP         
Sub-Investigator: Lynne Williams, MBChB MRCP PhD         
Sub-Investigator: Sharad Agarwal, MD FRCP         
Sub-Investigator: Bobby Agrawal, BMBS FRCS FRCR         
Sub-Investigator: Doris M Rassl, MBBS MRCPath         
Sponsors and Collaborators
Mayo Clinic
Cambridge University Hospitals NHS Foundation Trust
Investigators
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Principal Investigator: Peter A Brady, MD FRCP FHRS Mayo Clinic

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Responsible Party: Grace Lin, Director of Heart Failure Services, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03049254     History of Changes
Other Study ID Numbers: 15-002607 17-004169
First Posted: February 10, 2017    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Cardiovascular Diseases
Heart Diseases
Cardiomyopathies
Heart Arrest
Tachycardia
Sarcoidosis
Tachycardia, Ventricular
Death
Cardiomyopathy, Dilated
Death, Sudden, Cardiac
Arrhythmias, Cardiac
Myocarditis
Cardiovascular Abnormalities
Arrhythmogenic Right Ventricular Dysplasia
Cardiac Conduction System Disease
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Cardiomegaly
Death, Sudden
Congenital Abnormalities
Heart Defects, Congenital