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

August 26, 2016 updated by: Central Hospital, Nancy, France

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • France
      • Vandoeuvre Les Nancy, France
        • Recruiting
        • Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois
        • Contact:
          • Etienne ALIOT, Pr

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Atrial fibrillation in normal heart
Patients having atrial fibrillation in normal heart
Biological: Blood sample
Other: Quantification assay of adenosine and methionine cycle metabolites
Genetic: Polymorphism analysis of genes related to adenosine metabolism and methionine cycle
Other: Quantitative and qualitative nutritional evaluation
Questionnaire on consumption of 208 foods and drinks
ACTIVE_COMPARATOR: Control
Patients having a junctional supraventricular tachycardia in normal heart
Biological: Blood sample
Other: Quantification assay of adenosine and methionine cycle metabolites
Genetic: Polymorphism analysis of genes related to adenosine metabolism and methionine cycle
Other: Quantitative and qualitative nutritional evaluation
Questionnaire on consumption of 208 foods and drinks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of genetic polymorphisms related to adenosine and methionine metabolism
Time Frame: day 0
Increase of frequency in patients having an AF in normal heart
day 0
Levels of adenosine and methionine cycle nutritional and metabolic determinants
Time Frame: day 0
day 0

Secondary Outcome Measures

Outcome Measure
Time Frame
Level of nutritional and methionine cycle metabolic determinants according to thromboembolic complications of AF in normal heart
Time Frame: day 0
day 0

Collaborators and Investigators

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

Sponsor

Central Hospital, Nancy, France

Investigators

  • Principal Investigator: Etienne ALIOT, Pr, Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois, France

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

March 1, 2010

Primary Completion (ANTICIPATED)

January 1, 2017

Study Completion (ANTICIPATED)

October 1, 2017

Study Registration Dates

First Submitted

August 23, 2016

First Submitted That Met QC Criteria

August 26, 2016

First Posted (ESTIMATE)

August 31, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

August 31, 2016

Last Update Submitted That Met QC Criteria

August 26, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009-A01197-50

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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