Trial Outcomes & Findings for Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders (NCT NCT04257994)

NCT ID: NCT04257994

Last Updated: 2025-03-11

Results Overview

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.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Target enrollment: 26 participants
• Primary outcome timeframe: 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.
• Results posted on: 2025-03-11

Participant Flow

Participant milestones

Measure	Predisposed for Heritable Cardiac Disorder Eligible participants will either have a diagnosis of a heritable heart condition or be a relative of a sudden cardiac death victim/ person diagnosed with a heritable heart condition
Overall Study STARTED	26
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders

Baseline characteristics by cohort

Measure	Patients With Arrhythmic Disorders n=18 Participants 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. obtaining a buccal smear sample: A sample will be taken from the inside of the participants' cheeks using a soft brush
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	32 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United Kingdom	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: bearing a heritable heart disease mutation or be a first degree relative of SCD victim of carrier of heart disease mutation

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.

Outcome measures

Measure	Predisposed for Heritable Cardiac Disorder n=26 Participants Eligible participants will either have a diagnosis of a heritable heart condition or by at risk of developing an arrhythmic disorder (ie. are carriers of disease-causing mutations)
Alteration of Key Protein Distribution	26 Participants

SECONDARY outcome

Timeframe: 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.

A potential secondary outcome of the research is whether the investigators can correlate protein distribution in the buccal mucosa with specific genotypes. The investigators' preliminary results on the cohort of patients with ACM suggest that mutations in different genes result in different protein distribution patterns within the buccal mucosa. Being able to predict the gene bearing the disease-causing mutation will significantly reduce the time and cost of genetic sequencing. Identifying the specific gene underlying a heritable arrhythmic disorder is of pivotal importance as increasingly developing genotype/phenotype correlations help individualized risk identification and patient management.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Another potential outcome has to do with the effect changes in the patients' treatment plans may have on Cx43 distribution. Cx43 is the major gap junction protein responsible for the electrical coupling of the cells. It has been shown that patients with arrhythmic disorders show decreased distribution of Cx43 at the cell borders in their hearts and this has been associated with an increased risk for arrhythmias. The investigators' preliminary studies show that patients with cardiomyopathies show Cx43 remodeling in their buccal mucosa. If a patient seen at the arrhythmia service of St. George's shows Cx43 remodeling during initial sampling and in a follow-up visit his clinical care team deems necessary to change his treatment plan the investigators would like to study Cx43 distribution again during one of his/hers follow up visits. If the new treatment plan results in restoration of Cx43, this finding may be an indication of successful arrhythmia management.

Outcome measures

Outcome data not reported

Adverse Events

Predisposed for Heritable Cardiac Disorder

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Predisposed for Heritable Cardiac Disorder n=18 participants at risk Eligible participants will either have a diagnosis of a heritable heart condition or be a relative of a sudden cardiac death victim/ person diagnosed with a heritable heart condition
Congenital, familial and genetic disorders no adverse events recorded	0.00% 0/18 • through study completion an average of 1 year no adverse events recorded

Other adverse events

Adverse event data not reported

Additional Information

Dr Angeliki Asimaki

St George's, University of London

Phone: +447484764641

Email: aasimaki@sgul.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place