Artificial Intelligence for the Prioritization of Genetic Background in Brugada Syndrome (AI4Cardio)

April 18, 2024 updated by: Chiara Di Resta, IRCCS San Raffaele

The Use of Artificial Intelligence for the Prioritization of Causative Genetic Background in a Brugada Syndrome Cohort: an Observational Retrospective Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • IRCCS San Raffaele
      • Milan, Italy
        • Milano-Bicocca University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

200 BS patients.

Description

Inclusion Criteria:

  • The 200 BS patients have been selected and clinically evaluated based on the presence of a type I electrocardiogram (ECG), either spontaneous or induced by flecainide or ajmaline.

Exclusion Criteria:

  • No exclusion criteria are adopted for this study. The entire previously sequenced cohort of 200 BS patients will be investigated and considered, exploiting AI approach for the prioritization of the sequencing available data.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
BrS Patients
The 200 BS patients have been selected and clinically evaluated by Department of Cardiac Electrophysiology and Arrhythmology, San Raffaele Hospital, for the presence of a type I electrocardiogram (ECG), either spontaneous or induced by flecainide or ajmaline. Morphologic and functional characteristics of the heart have been analysed in all patients by trans-thoracic echocardiography and stress test to rule out patients with Arrhythmogenic Right Ventricular Dysplasia and ischemic heart disease. Among clinical characteristics, 12-lead signal averaged ECG parameters and all possible risk factors have been evaluated. Electrophysiological study has been performed in spontaneous BS pattern 1 ECG patients or patients with induced BS pattern 1 ECG and at least one risk factor. In patients with higher susceptibility for the induced Ventricular Tachycardia, ICD has been implanted.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
New candidate genes, likely associated with Brugada Syndrome using an AI based approach.
Time Frame: 1 year
Prioritization of genetic variations underlying the BS phenotype: the whole exome data of 200 BS previously sequenced will be prioritized using an AI- based approach, developed by the collaborators in UniMIB.
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Identification of genetic risk factors associated with the worse phenotype.
Time Frame: 1 year
Correlation of the new putative genes and the clinical variables, previously collected in a comprehensive database for this study.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS San Raffaele

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Chiara Di Resta, PhD, IRCCS San Raffaele Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 19, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 6, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 6, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 16, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 19, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 19, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AI4Cardio

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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