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

NCT ID: NCT02885740

Last Updated: 2016-08-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2017-10-31

Brief Summary

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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

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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.

Conditions

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Atrial Fibrillation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Atrial fibrillation in normal heart

Patients having atrial fibrillation in normal heart

Group Type EXPERIMENTAL

Quantification assay of adenosine and methionine cycle metabolites

Intervention Type OTHER

Polymorphism analysis of genes related to adenosine metabolism and methionine cycle

Intervention Type GENETIC

Quantitative and qualitative nutritional evaluation

Intervention Type OTHER

Questionnaire on consumption of 208 foods and drinks

Blood sample

Intervention Type BIOLOGICAL

Control

Patients having a junctional supraventricular tachycardia in normal heart

Group Type ACTIVE_COMPARATOR

Quantification assay of adenosine and methionine cycle metabolites

Intervention Type OTHER

Polymorphism analysis of genes related to adenosine metabolism and methionine cycle

Intervention Type GENETIC

Quantitative and qualitative nutritional evaluation

Intervention Type OTHER

Questionnaire on consumption of 208 foods and drinks

Blood sample

Intervention Type BIOLOGICAL

Interventions

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Quantification assay of adenosine and methionine cycle metabolites

Intervention Type OTHER

Polymorphism analysis of genes related to adenosine metabolism and methionine cycle

Intervention Type GENETIC

Quantitative and qualitative nutritional evaluation

Questionnaire on consumption of 208 foods and drinks

Intervention Type OTHER

Blood sample

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Central Hospital, Nancy, France

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Etienne ALIOT, Pr

Role: PRINCIPAL_INVESTIGATOR

Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois, France

Locations

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Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Etienne ALIOT, Pr

Role: CONTACT

Email: [email protected]

Facility Contacts

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Etienne ALIOT, Pr

Role: primary

Other Identifiers

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2009-A01197-50

Identifier Type: -

Identifier Source: org_study_id