Role and Interactions of Adenosine, Receptors, Methionine Cycle Nutritional, Metabolic and Genetic Determinants in the Onset of Atrial Fibrillation in Normal Heart — FACS  

Atrial Fibrillation Clinical Trial

Official title: Role and Interactions of Adenosine, Receptors, Methionine Cycle Nutritional, Metabolic and Genetic Determinants in the Onset of Atrial Fibrillation in Normal Heart

Status Recruiting

Clinical Trial Summary

The purpose of this study is to analyze the association of atrial fibrillation onset in normal heart and:

• Genetic determinants (genes of receptors, enzymes involved in synthesis and degradation, genes of bioavailability of coenzymes and nutritional precursors)

• Metabolic determinants of adenosine and methionine cycles

• Nutritional determinants.

Secondary purposes are:

• Analysis of physiopathologic mechanisms of AF in normal hearts and adenosine metabolisms and its interaction with methionine metabolism, according to identified genetic determinants

• Analysis of blood markers of adenosine and methionine metabolites as phenotypic markers of detected polymorphisms

• Evaluate the role of adenosine receptors in AF onset

Clinical Trial Description

Atrial fibrillation (AF) is the most frequent arrhythmia and its causes are not well known. Experimental and clinical studies showed that activation of parasympathetic system can induce and maintain AF. Adenosine is a cardiovascular modulator with effects on vascular tonus and activation of nodal tissue through the activation of A1, A2A, A2B et A3 receptors. Intracellular production of adenosine is directly dependent (30%) on the hydrolysis of S-adenosylhomocysteine (SAH) by S-adenosylhomocysteine hydrolase in methionine cycle. Cellular production of adenosine depends on ratio SAH/S-adenosylmethionine (SAM) and modulates the expression of receptors. Other potential interactions between this 2 metabolisms in AF are: 1) ratio SAM/SAH influences epigenetic mechanisms that can modify the expression of candidate genes involved in synaptic transmission and potassium canals, 2) ratio SAM/SAH influences also the cellular production of homocysteine with effects on cellular polarization, 3) adenosine and homocysteine are factors involved in thrombophilia and potentially associated to thromboembolic complications of AF.

This study will evaluate the genetic (micro SNP-array) and adenosine and methionine metabolic determinants in the physiopathology of AF in normal hearts.

Perspectives of this study are the prevention of AF in normal hearts through a nutritional and metabolic approach in subjects having a multigenic predisposition. ;

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Atrial Fibrillation

• NCT number: NCT02885740
• Study type: Interventional
• Source: Central Hospital, Nancy, France
• Contact: Etienne ALIOT, Pr
• Email: e.aliot@chru-nancy.fr
• Status: Recruiting
• Phase: N/A
• Start date: March 2010
• Completion date: October 2017