Clinical trial NCT02885740: Role and Interactions of Adenosine, Receptors, Methionine Cycle Nutritional, Metabolic and Genetic Determinants in the Onset of Atrial Fibrillation in Normal Heart
Official title: Role and Interactions of Adenosine, Receptors, Methionine Cycle Nutritional, Metabolic and Genetic Determinants in the Onset of Atrial Fibrillation in Normal Heart
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atrial Fibrillation
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2016-08-31
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Informed consent
* Affiliation to French social security plan

AF in normal heart:

- Atrial fibrillation in normal heart

Control:

- Junctional supraventricular tachycardia in normal heart

Normal heart: absence of macroscopic cardiomyopathy (echocardiography and normal ejection fraction)

Exclusion Criteria:

* Considerable consumption of coffee (\> 50 mg/day, 15 cups/day)
* Actual administration of drugs interfering with adenosine metabolism: dipyridamole and methotrexate
* Actual administration interfering with methionine metabolism: folates, methotrexate and anticonvulsants
* Known renal insufficiency
* Known hypo- or hyperthyroidism
* Refusal or impossibility of informed consent
* Pregnant or breastfeeding women
* Person deprived of liberty
* Person under legal protection or not able to consent
* Person in emergency situation

Primary outcomes:
measure: Frequency of genetic polymorphisms related to adenosine and methionine metabolism
timeFrame: day 0
measure: Levels of adenosine and methionine cycle nutritional and metabolic determinants
timeFrame: day 0
Secondary outcomes:
measure: Level of nutritional and methionine cycle metabolic determinants according to thromboembolic complications of AF in normal heart
timeFrame: day 0
Other outcomes:
Locations:
city: Vandoeuvre Les Nancy
country: France
facility: Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois
Study officials:
affiliation: Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois, France
name: Etienne ALIOT, Pr
role: PRINCIPAL_INVESTIGATOR
References: