Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders

NCT04257994 | Active Not Recruiting Results

• 1 other identifier: 16.0099
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Every week in the UK, 12 apparently healthy and fit individuals under the age of 35 die suddenly, a tragic event known as sudden cardiac death (SCD). The investigators have shown that heritable cardiac disorders affect the distribution of proteins at the cardiac cell-cell junctions, the areas where cardiac cells are mechanically and electrically coupled. This knowledge has helped the investigators diagnose specific heart disorders in individuals thus reducing the risk and incidence of SCD. Yet, the primary material required is a heart sample. A heart biopsy is an invasive process that comes with risks and is not performed unless absolutely necessary. And it is impossible to obtain a heart sample from an individual that may be carrying a disease-causing mutation (and hence be at risk of SCD) but does not yet show evidence of disease manifestation. The investigators recently showed that buccal cells show changes in protein distribution equivalent to those exhibited by the heart,hence providing them with a surrogate tissue for the myocardium. The investigators aim to use buccal smears as a means to identify those at risk of SCD. Patients regularly seen at the cardiology clinics at St. George's Hospital can participate in the study. The investigators shall take a buccal smear simply by rubbing a soft brush at the inside of their cheek and smearing it on a slide. Most individuals willing to participate in the study will only have to provide the investigators with a sample once. However, in selected cases (for instance, if the patients show disease progression or have a change in medication) they may be asked to provide the investigators with a subsequent sample during one of their scheduled follow-up visits. The process takes only a few seconds, is totally risk- and pain-free and it is anticipated to have great implications in diagnosis and patient management.

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Brugada Syndrome; Cardiac Channelopathy

Keywords

cardiac arrhythmias

Outcome Measures

Primary Outcomes (1)

• Alteration of Key Protein Distribution

  We recruit individuals that have propensity to an arrhythmic disorder (ie. they are carriers of disease-causing mutations) or they have been already diagnosed with a heritable heart condition. The primary outcome measure is whether key proteins show altered localization in the eligible participants. We are reporting the number of participants that did show altered protein distribution at baseline. There is no unit of measurement for this outcome. Cheek smears are subjected to immunofluorescence staining and examined under a confocal microscope. The technique has been optimized to show a binary outcome: a protein is either at its normal location or not.

  This is a longitudinal study. Each participant will provide cheek smears at recruitment to assess baseline protein distribution. Thereafter, each participant will be asked to provide follow-up samples every 6 months for the duration of the study.

Secondary Outcomes (2)

• Correlation of Protein Distribution With Participants' Genotype

  This is a longitudinal study. Each participant will provide cheek smears at recruitment to assess baseline protein distribution. Thereafter, each participant will be asked to provide follow-up samples every 6 months for the duration of the study.

• Correlation of Treatments With Cx43 Distribution

  This is a longitudinal study. Each participant will provide cheek smears at recruitment to assess baseline protein distribution. Thereafter, each participant will be asked to provide follow-up samples every 6 months for the duration of the study.

Study Arms (1)

patients with arrhythmic disorders

Participants will include patients diagnosed with a heritable arrhythmic disorder (including arrhythmogenic, hypertrophic and dilated cardiomyopathy, cardiac sarcoidosis as well as cardiac channelopathies; Long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) followed at the Inherited Cardiac Conditions (ICC) service of St. George's University Hospitals NHS Foundation Trust as well as family members of victims of SCD evaluated at the same clinic for risk assessment and diagnosis.

Diagnostic Test: obtaining a buccal smear sample

Interventions

obtaining a buccal smear sample DIAGNOSTIC_TEST

A sample will be taken from the inside of the participants' cheeks using a soft brush

patients with arrhythmic disorders

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will include individuals that have arrhythmic disorders or are being evaluated for arrhythmic disorders due to a family history of sudden cardiac death at the cardiology center of St George's.

You may qualify if:

• Family members of victims of SCD evaluated at the same clinic for risk assessment and diagnosis. These groups include both individuals with clear disease manifestation (termed "affected") as shown by conventional diagnostic approaches (electrocardiography, echocardiography, cardiac MRI, Holter monitoring) as well as potential carriers of disease-causing mutations who, however, may not/not yet manifest any overt sign of cardiovascular abnormalities (termed "carriers"). These are typically family members of probands diagnosed with a heritable arrhythmic disorder or family members of a sudden cardiac death victim.
• All individuals that fall in the above categories will be included regardless of their management (medication, devices, and surgical procedures).
• Individuals with co-existing conditions will also be included and their medical history will be taken into account when interpreting the results of the immunohistochemical analysis.
• Adult individuals (\>18 years of age).
• Pregnant women will be included as the approach used is not in any way harmful or uncomfortable.
• All individuals must have provided the study team with a signed informed consent in order to participate in the study.

You may not qualify if:

• Individuals lacking decisional capacity.
• Individuals with non-heritable, non-arrhythmic cardiac disorders (such as ischemic heart disease or inflammatory disorders) followed at St. George's University Hospitals NHS Foundation Trust.
• Non-English speakers will be excluded from the study unless a translator is present who can thoroughly explain to them the research question/plan in order for them to provide an informed consent.

Sponsors & Collaborators

• St. George's Hospital, London: lead

Study Sites (1)

St George'S Hospital

London, SW17 0RE, United Kingdom

Location

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Brugada Syndrome; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiomyopathies; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiac Conduction System Disease; Genetic Diseases, Inborn; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Angeliki Asimaki
• Organization: St George's, University of London

aasimaki@sgul.ac.uk

+447484764641

Study Officials

• Angeliki Asimaki

  St George's, University of London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senio Lecturer in Cardiac Morphology and Sudden Death

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: February 6, 2020
• Study Start: October 15, 2017
• Primary Completion: March 30, 2024
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 11, 2025
• Results First Posted: February 17, 2025

Record last verified: 2025-02

Locations

GB (1)