Association of Genetic Polymorphisms With Atrial Fibrosis and Thrombogenic Substrate in Patients With Non-valvular Atrial Fibrillation (ANATOLI-AF)

June 15, 2018 updated by: Sercan Okutucu, Memorial Ankara Hospital

AssociatioN of Genetic Polymorphisms With ATrial fibrOsis and Thrombogenic Substrate in Patients With Non-vaLvular atrIAl Fibrillation

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. Emerging data suggests that common genetic variants are associated with the development of AF. The main feature of the structural remodelling in AF is atrial fibrosis and is considered the substrate for AF perpetuation. Genome-wide association studies suggest that AF-susceptibility variants may modulate atrial fibrosis. However, the association between atrial fibrosis and genetic polymorphisms in humans has not yet been specifically investigated. In this study, we plan to investigate the relationship between genetic polymorphisms, atrial fibrosis and other components of thrombogenic substrate in patients with non-valvular AF. Primary objectives of this study are to assess associations between (i) polymorphic genetic variants and atrial fibrosis (detected by magnetic resonance imaging), (ii) polymorphic genetic variants and components of thrombogenic substrate (inflammation, endothelial function, prothrombotic state, atrial functions).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. Emerging data suggests that common genetic variants are associated with the development of AF. The main feature of the structural remodelling in AF is atrial fibrosis and is considered the substrate for AF perpetuation. Genome-wide association studies suggest that AF-susceptibility variants may modulate atrial fibrosis. However, the association between atrial fibrosis and genetic polymorphisms in humans has not yet been specifically investigated. In this study, we plan to investigate the relationship between genetic polymorphisms, atrial fibrosis and other components of thrombogenic substrate in patients with non-valvular AF. Primary objectives of this study are to assess associations between (i) polymorphic genetic variants and atrial fibrosis (detected by magnetic resonance imaging), (ii) polymorphic genetic variants and components of thrombogenic substrate (inflammation, endothelial function, prothrombotic state, atrial functions). Patients are planned to be recruited from four major cardiology departments: Memorial Ankara Hospital, Ministry of Health Subspecialty Training Hospital of Turkey, Ufuk University and Gazi University hospitals. Key variables that will be recorded include the clinical, contrast-enhanced MRI, biomarkers, echocardiographic and assessment of endothelial function. All statistical analyses will be conducted using Stata version 11.0 (StataCorp, College Station, TX). Univariate and multivariate regression models will be used to determine the odds ratio of each variable to assess the association of the clinical and laboratory parameters, and genotype profiles with the presence of LA fibrosis. Furthermore, data mining methods like support vector machines and/or random forests are planned to be used for detecting the impact of each potential predictor on the risk of LA fibrosis. Additionally, to determine the effect of different alleles of the identified risk SNPs, 2-way and 3-way multi dimensionality reduction (MDR) analysis will be performed. Bioinformatics investigations to determine SNP-SNP, SNP-gene and SNP-Phenotype interactions will be performed by combined p-value and biological network analysis.

Study Type

Observational

Enrollment (Anticipated)

225

Contacts and Locations

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

Study Contact

Study Contact Backup

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

Ages Eligible for Study

17 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Study population will include patients with documented AF (Paroxysmal or Persistent) over the age of 18. Patients are planned to be recruited from four major cardiology departments: Memorial Ankara Hospital, Ministry of Health Subspecialty Training Hospital of Turkey, Ufuk University and Gazi University hospitals.

Description

Inclusion Criteria:

  • >18 years
  • Documented AF
  • Paroxysmal and persistent AF

Exclusion Criteria:

  • Patients with infectious or non-infectious inflammatory disease
  • Patients with structural heart disease
  • Acute coronary syndrome
  • Severe liver and kidney dysfunction
  • Cancer
  • Immune disorders
  • Surgery and stroke within six months

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Associations between polymorphic genetic variants and atrial fibrosis
Time Frame: Through study completion, an average of 1 year
(detected by MRI)
Through study completion, an average of 1 year
Associations between polymorphic genetic variants and components of thrombogenic substrate
Time Frame: Through study completion, an average of 1 year
Thrombogenic substrate (inflammation, endothelial function, prothrombotic state, atrial functions)
Through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Memorial Ankara Hospital

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 (Anticipated)

July 1, 2018

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

June 6, 2018

First Submitted That Met QC Criteria

June 6, 2018

First Posted (Actual)

June 18, 2018

Study Record Updates

Last Update Posted (Actual)

June 19, 2018

Last Update Submitted That Met QC Criteria

June 15, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MANK200801

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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