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

Sudden Cardiac Death Clinical Trial

— ICDGPSS  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05582252
• Other study ID #: KINASK-ICDGPSS-EICCG2210
• Secondary ID: DN2022/400-MN202
• Status: Not yet recruiting
• Start date: February 2023
• Est. completion date: March 2025

Study information

• Verified date: October 2022
• Source: Selcuk University
• Contact: EBRU M Ozdemir, MD.
• Phone: ++905063510721
• Email: ebru.ozdemir[@]selcuk.edu.tr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2500
• Est. completion date: March 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Arrythmia
• Death
• Death, Sudden, Cardiac
• ICD
• Sudden Cardiac Death

Intervention

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.

Locations

Country	Name	City	State
Turkey	Selcuk University Genetic Department Faculty of Medicine	Konya

Sponsors (5)

Lead Sponsor	Collaborator
Selcuk University	Ankara University, Dokuz Eylul University, Selcuk University Cardiology Department of Medicine Faculty, TC Erciyes University

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	comprehensive local demographic statistics	since a large-scale study is desired, valuable domestic demographic statistical data can be achieved	2024DEC
Primary	Revealing SNP variants related to phenotypic measurement factors	ICD Shock, Sudden Cardiac Death, Ventricular Arrythmia and ICD prognosis related genetic polymorphism variant	2024MAY
Primary	GENOPHENOTYPIC risk stratification	Results of genotype and phenotype statistical analysis	2024DEC
Primary	Comprehensive genophenotypic scoring system formula	a formula that is based on genetic and phenotypic parameters that can be used as criteria for ICD implantation indication	2025MARCH
Secondary	offering a comprehensive cardiogenetic kit	a kit that is based on the Illumina bead chip Infinium Microarray technology and can be used for research, clinical screening and diagnosis	2025MARCH