Clinical trial NCT05582252: Genome-Wide Association Study With the Aim of Implantable Cardioverter Defibrillator Implantation Genophenotypic Risk Stratification
Official title: The Comprehensive Investigation to Define a New Scoring System for ICD Implantation Based on Genotypic and Phenotypic Criteria; A Multidisciplinary and Multicentral Genome-Wide Association Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: ICD
Arrythmia
Sudden Cardiac Death
Keywords: Implantable Cardioverter Defibrillators
Ventricular Arrhythmia
Sudden Cardiac Death
Cardiogenomics
Cardiogenetics
GWAS
Genetic Polymorphism
Lead sponsor: Selcuk University
Sponsor class: OTHER
Collaborators: name: Ankara University
name: TC Erciyes University
name: Dokuz Eylul University
name: Selcuk University Cardiology Department of Medicine Faculty
First posted: 2022-10-17
Enrollment: 2500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population are the ICD-implanted patients according to exclusion and inclusion criteria. No randomization will be done for patient selection and group allocation (the validation stage will be done by randomization). An extra-healthy volunteer will be included for bioinformatic data analysis.

Brief summary: This clinical study will be conducted with funding from European Innovation Council(EIC) after approval of the fund grant and is part of our organization's European Pathfinder Project(Ref: HORIZON-EIC-2022-PATHFINDERCHALLENGES-01). The clinical study step of this project will be started in a retrospective time prospective manner by gathering the phenotypic(clinical measuring factors) data from patients who underwent ICD implantation therapy. The study will be done as a case-control type in which patients who did not get any shocks in 6 months post-implantation will be allocated to the control group. A customized and highly specific cardiogenomics panel will be designed and ordered to be specially manufactured as a standard kit by Illumina® (San Diego, California, U.S.) following an exhaustive investigation for collecting genetic variants which correlated to cardiovascular development. Mentioned kit bears the standard and validated technology which is part of the genetic tests routine and is being produced by Illumina® incorporate. However, as an option manufacturer is designing custom kits for research purposes by getting the desired variant lists using the same technology. Accordingly, enrolled patients in the study will be prospectively sampled ( Non-Invasive saliva sampling) for getting genetically analysed by Illumina®'s Infinium Assay Microarray platform with fully customized 700,000 single nucleotide polymorphism kits. The result of this sampling will be data and statistically analysed in a genome-wide association study(GWAS) manner by considering the 5x10-8 p.value and will be associated with each phenotypic parameter. Accordingly, the study will assess the genetic risk stratification in ICD patients in a much more detailed fashion. Following this assessment genophenotypic statistical analysed will be done to combine both parameters and generate a formula for scoring the indicator factors based on each odds ratio. Correspondingly, this new scaling formula will be analysed, verified and validated further by a randomized sampling of the population in our study before being stated. Additionally, This study will not only help to improve current genetic polymorphism clinal significant status (pathogenicity and significance of variant) but also can associate new markers with high significance that can be directly used in clinical screening, diagnosis or clinical approaches.


Eligibility criteria: Inclusion Criteria:

* ICD-implanted patients (both for primary and secondary intervention)
* Being a volunteer for the study
* Adequacy in understanding the study risks and accepting the Informed Consent Form
* Official acceptance of the legal and official parents (both father and mother), If younger than 18 years old

Exclusion Criteria:

* The patient who does not volunteer to involve to the study.
* Diagnosis of underlying arrhythmogenic disease (Structural Heart disease, Brugada, Arrhythmogenic right ventricular dysplasia, etc.)
* Development of electric shock due to acute coronary syndrome
* Atrial Fibrillation (AFib) With Rapid Ventricular Response
* Electric shock in patients with electrolyte imbalance-induced VT/VF
* Electric Shock in a patient with acute myocarditis-induced ventricular arrhythmias
* Patients that had an electric shock because of pacing / ATP ramp-induced VT (RV/CRT Pacing)

Primary outcomes:
measure: Revealing SNP variants related to phenotypic measurement factors
timeFrame: 2024MAY
measure: GENOPHENOTYPIC risk stratification
timeFrame: 2024DEC
measure: Comprehensive genophenotypic scoring system formula
timeFrame: 2025MARCH
Secondary outcomes:
measure: offering a comprehensive cardiogenetic kit
timeFrame: 2025MARCH
Other outcomes:
measure: comprehensive local demographic statistics
timeFrame: 2024DEC
Locations:
city: Konya
country: Turkey
facility: Selcuk University Genetic Department Faculty of Medicine
Study officials:
References: