Clinical Trials Logo

Clinical Trial Summary

Brugada Syndrome (BS) is an inherited heart condition that can cause sudden cardiac arrest in young individuals. It's diagnosed through specific changes seen on an electrocardiogram (ECG). Currently, the only treatment option is a cardioverter defibrillator (ICD). Despite advances, much about BS remains unclear, including its genetic basis. This study aims to use advanced genetic sequencing and artificial intelligence to uncover new genetic factors contributing to BS. By understanding these factors better, we hope to improve risk assessment and treatment for affected individuals.


Clinical Trial Description

Brugada Syndrome (BS) is an inherited cardiac electrical disorder that can cause syncope and sudden cardiac arrest in young asymptomatic individuals. It is suspected to contribute to 4-12% of cases of sudden cardiac death in the general population. Diagnosis relies on identifying a type I ECG pattern characterized by ST-segment elevation with a coved morphology in the right precordial leads. The prevalence in Western countries is estimated at 1:5000. Currently, implantation of a cardioverter defibrillator (ICD) is the only treatment option, but risk stratification guidelines remain incomplete, particularly for asymptomatic individuals. BS is inherited as an autosomal dominant trait with incomplete penetrance. While 23 genes have been associated with BS susceptibility, 70% of patients remain genetically uncharacterized, suggesting a more complex inheritance pattern. Genetics have not been incorporated into risk stratification guidelines, despite evidence linking certain genetic variants to higher arrhythmic risk. This knowledge gap underscores the importance of expanding our understanding of BS genetics to enhance diagnostic sensitivity and patient management. This protocol builds upon preliminary data from a study granted by the Italian Ministry of Health (GR-2016-02362316), in which next-generation sequencing (NGS) was used to investigate the entire coding regions (Whole Exome Sequencing_WES) of 200 BS patients. The study aimed to identify new BS candidate genes and characterize the genetic basis of the condition. The cohort was selected based on the presence of a type I ECG, confirmed either spontaneously or induced by flecainide or ajmaline. Patients underwent thorough cardiac evaluations to rule out other conditions. Follow-up included yearly assessments and more frequent evaluations for patients with a higher risk of ventricular tachycardia. A large number of genetic variants were identified by exploiting WES, prompting the use of Artificial Intelligence (AI) to prioritize the sequencing data. AI techniques, including advanced algorithms and machine learning, can streamline the identification of potentially disease-causing genetic variations by filtering out common variants, predicting pathogenicity, and integrating clinical data. Given that over 70% of BS patients remain genetically undiagnosed, high-throughput sequencing approaches are crucial for a comprehensive understanding of BS genetics. This study aims to contribute to the identification of new genetic factors and improve risk stratification for affected patients. All sequencing data for this project have been generated and will be analyzed using AI, with no further patients to be enrolled or sequenced. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT06376552
Study type Observational
Source IRCCS San Raffaele
Contact
Status Completed
Phase
Start date December 19, 2018
Completion date June 6, 2022

See also
  Status Clinical Trial Phase
Recruiting NCT05048602 - Drug-induced Brugada Syndrome Research Database
Terminated NCT00701077 - DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome Phase 3
Recruiting NCT03435393 - Ripple Mapping for Epicardial Mapping of Brugada Syndrome N/A
Active, not recruiting NCT02933437 - The Response To Ajmaline Provocation in Healthy Subjects Phase 2
Active, not recruiting NCT04257994 - Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
Recruiting NCT05685134 - Invasive and Clinical Features in Patients With Brugada Syndrome Undergoing Catheter Ablation N/A
Recruiting NCT04580992 - Defining the Electrocardiographic Effect of Propofol on the Ajmaline Provocation Drug Challenge: A Prospective Trial
Completed NCT02641431 - Epicardial Ablation in Brugada Syndrome N/A
Completed NCT03182777 - Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies N/A
Completed NCT00292032 - Registry of Unexplained Cardiac Arrest
Completed NCT04124237 - Long Term Monitoring for Risk of Sudden Death
Completed NCT02344277 - Evaluation of Subcutaneous Implantable Cardiac Defibrillator in Brugada Patients
Completed NCT04650009 - Physical Activity in Children With Inherited Cardiac Diseases
Recruiting NCT04808193 - European Perioperative Brugada Survey N/A
Recruiting NCT03491475 - Echocardiography During Ajmaline Test
Recruiting NCT05521451 - Clinical Cohort Study - TRUST
Recruiting NCT03485508 - The Brugada Syndrome: a Follow-up Study
Completed NCT00702117 - Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias Phase 4
Recruiting NCT02704416 - Ablation in Brugada Syndrome for the Prevention of VF N/A
Recruiting NCT03775954 - Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise