DNA Methylation in Brugada Syndrome and Risk of Sudden Cardiac Death (ANDROMEDA)

DNA Methylation in Brugada Syndrome and Risk of Sudden Cardiac Death (ANDROMEDA)

The goal of this observational study is to evaluate if there are differences in DNA methylation of peripheral blood in patients with Brugada syndrome and healthy subjects. The main question it aims to answer is:

Does DNA methylation changes distinguish Brugada patients from healthy controls?

Does DNA methylation changes distinguish Brugada patients with high versus low risk of sudden cardiac death?

Study Overview

• Status: Not yet recruiting
• Conditions: Sudden Cardiac Death Due to Cardiac Arrhythmia; Brugada Syndrome

Detailed Description

The Investigators will enroll 10 patients with Brugada syndrome and 10 age and sex matched healthy controls. We will collect 5 mL of peripheral blood and will analyze genome-wide DNA methylation via EPIC array platform. Bioinformatic algorithms and network analysis will be applied to identify possible diagnostic and predictive biomarkers.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Giuditta Benincasa, PhD; Phone Number: 0815667916; Email: giuditta.benincasa@unicampania.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with Brugada syndrome attended the Cardiology Dept. at University of Campania "L. Vanvitelli", Monaldi Hospital (Naples, Italy). The control group consisted of unrelated age- and sex-matched healthy subjects as volunteer blood donors attending the U.O.C. Divisione di Immunologia Clinica, Immunoematologia, Medicina Trasfusionale at University of Campania "L. Vanvitelli" (Naples, Italy).

Description

Inclusion Criteria:

• Brugada syndrome was confirmed when the 12-lead ECG showed ST-segment elevation with a type-1 morphology of ≥2 mm in ≥1 right precordial lead either spontaneously or after a provocative drug test (intravenous administration of a Class I antiarrhythmic) in the absence of any structural heart disease.
• >18 years
• Unrelated patients

Exclusion Criteria:

• Related patients
• Not type 1 Br patter

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy subjects; The control group consisted of unrelated age- and sex-matched healthy subjects as volunteer blood donors with no evidence of any ECG abnormalities, inherited arrhythmia, genetic cardiomyopathy, and no history of ventricular arrhythmia, unexplained syncope, unexplained sudden cardiac arrest/ death.
Brugada patients; Brugada syndrome was confirmed when the 12-lead ECG showed ST-segment elevation with a type-1 morphology of ≥2 mm in ≥1 right precordial lead either spontaneously or after a provocative drug test (intravenous administration of a Class I antiarrhythmic) in the absence of any structural heart disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of differentially methylated genes as assessed by EPIC microarray	We will compare the methylation profiles of patients and controls in order to obtain a panel of differentially methylated genes.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of differentially methylated regions predicting the risk of sudden cardiac death	We will perform a subgroup analysis of Brugada patients (high vs. low risk of sudden cardiac death). ROC curve analysis will be performed to identify which differentially methylated genese may be useful to predict the risk of sudden cardiac death.	6 months

Collaborators and Investigators

• Sponsor: University of Campania Luigi Vanvitelli

Publications and helpful links

General Publications

• Benincasa G, Pepin ME, Russo V, Cacciatore F, D'Alto M, Argiento P, Romeo E, Chiappetti R, Laezza N, Wende AR, Schiattarella GG, Coscioni E, La Montagna A, Amarelli C, Maiello C, Golino P, Condorelli G, Napoli C. High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction. Basic Res Cardiol. 2024 Dec 27. doi: 10.1007/s00395-024-01093-7. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: March 15, 2025
• First Submitted That Met QC Criteria: March 15, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Liquid biopsy; Sudden cardiac death; DNA methylation; Brugada syndrome
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Genetic Diseases, Inborn; Disease; Heart Arrest; Death, Sudden; Brugada Syndrome; Syndrome; Death, Sudden, Cardiac; Death; Arrhythmias, Cardiac
• Other Study ID Numbers: Vanvitelli-Benincasa G; PE00000015 (Other Grant/Funding Number: National Recovery and Resilience Plan (NRRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No