ICDGPSS: Genome-Wide Association Study With the Aim of Implantable Cardioverter Defibrillator Implantation Genophenotypic Risk Stratification

Sponsor

Selcuk University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05582252

Collaborator

Ankara University (Other), TC Erciyes University (Other), Dokuz Eylul University (Other), Selcuk University Cardiology Department of Medicine Faculty (Other)

2,500

Enrollment

Location

24.9

Anticipated Duration (Months)

100.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
ICD Arrythmia Sudden Cardiac Death	Other: Non-Invasive saliva sampling

Study Design

Study Type:

Observational

Anticipated Enrollment :

2500 participants

Observational Model:

Case-Control

Time Perspective:

Other

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental group Patients with ICD who received at least one electric shock in 6 months after ICD implantation	Other: Non-Invasive saliva sampling There are two types of intervention in this ambidirectional study. Non-Invasive Saliva Sampling will be done for DNA extraction for the purpose of genetic analysis. This would be the prospective sampling and it's not part of the related medical centre's clinical routine. ICD that is already implanted in the patients and had been indicated by related medical centre's clinical routine approach. This is not a prospective approach to this study since the study would be retrospectively gathered phenotypic parameters from the hospital data records. Other Names: ICD
Control Group Patients with ICD who didnot received any electric shock in 6 months after ICD implantation	Other: Non-Invasive saliva sampling There are two types of intervention in this ambidirectional study. Non-Invasive Saliva Sampling will be done for DNA extraction for the purpose of genetic analysis. This would be the prospective sampling and it's not part of the related medical centre's clinical routine. ICD that is already implanted in the patients and had been indicated by related medical centre's clinical routine approach. This is not a prospective approach to this study since the study would be retrospectively gathered phenotypic parameters from the hospital data records. Other Names: ICD
Healthy Group Healthy Volunteers This group will be used for related bioinformatic analysis (DATA analysis stage) but not in statistical analysis	Other: Non-Invasive saliva sampling There are two types of intervention in this ambidirectional study. Non-Invasive Saliva Sampling will be done for DNA extraction for the purpose of genetic analysis. This would be the prospective sampling and it's not part of the related medical centre's clinical routine. ICD that is already implanted in the patients and had been indicated by related medical centre's clinical routine approach. This is not a prospective approach to this study since the study would be retrospectively gathered phenotypic parameters from the hospital data records. Other Names: ICD

Arm

Intervention/Treatment

Experimental group

Patients with ICD who received at least one electric shock in 6 months after ICD implantation

Other: Non-Invasive saliva sampling

There are two types of intervention in this ambidirectional study. Non-Invasive Saliva Sampling will be done for DNA extraction for the purpose of genetic analysis. This would be the prospective sampling and it's not part of the related medical centre's clinical routine. ICD that is already implanted in the patients and had been indicated by related medical centre's clinical routine approach. This is not a prospective approach to this study since the study would be retrospectively gathered phenotypic parameters from the hospital data records.

Other Names:

ICD

Control Group

Patients with ICD who didnot received any electric shock in 6 months after ICD implantation

Other: Non-Invasive saliva sampling

Other Names:

ICD

Healthy Group

Healthy Volunteers This group will be used for related bioinformatic analysis (DATA analysis stage) but not in statistical analysis

Other: Non-Invasive saliva sampling

Other Names:

ICD

Outcome Measures

Primary Outcome Measures

Revealing SNP variants related to phenotypic measurement factors [2024MAY]
ICD Shock, Sudden Cardiac Death, Ventricular Arrythmia and ICD prognosis related genetic polymorphism variant
GENOPHENOTYPIC risk stratification [2024DEC]
Results of genotype and phenotype statistical analysis
Comprehensive genophenotypic scoring system formula [2025MARCH]
a formula that is based on genetic and phenotypic parameters that can be used as criteria for ICD implantation indication

Secondary Outcome Measures

offering a comprehensive cardiogenetic kit [2025MARCH]
a kit that is based on the Illumina bead chip Infinium Microarray technology and can be used for research, clinical screening and diagnosis

Other Outcome Measures

comprehensive local demographic statistics [2024DEC]
since a large-scale study is desired, valuable domestic demographic statistical data can be achieved

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)