Role and Interactions of Adenosine, Receptors, Methionine... | NCT02885740

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

NCT02885740

Sponsor

Central Hospital, Nancy, France

Status

Unknown status

Last Update Posted

Aug 31, 2016Estimated

Enrollment

400Estimated

Phase

Not Applicable

Conditions

Atrial Fibrillation

Interventions

Quantification assay of adenosine and methionine cycle metabolites
Polymorphism analysis of genes related to adenosine metabolism and methionine cycle
Quantitative and qualitative nutritional evaluation
Blood sample

Countries

France

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Status Module

Record Verification Date

Aug 2016

Overall Recruitment Status or Expanded Access Status

Unknown status

Last Known Status

Recruiting

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Mar 2010

Primary Completion Date

Jan 2017Estimated

Completion Date

Oct 2017Estimated

First Submitted Date

Aug 23, 2016

First Submission Date that Met QC Criteria

Aug 26, 2016

First Posted Date

Aug 31, 2016Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Aug 26, 2016

Last Update Posted Date

Aug 31, 2016Estimated

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

400Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Atrial fibrillation in normal heart	Experimental	Patients having atrial fibrillation in normal heart	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 Biological: Blood sample
Control	Active Comparator	Patients having a junctional supraventricular tachycardia in normal heart	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 Biological: Blood sample

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Quantification assay of adenosine and methionine cycle metabolites	Other		Atrial fibrillation in normal heart Control

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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

Other Outcomes

Not provided

Eligibility Module

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

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
Etienne ALIOT, Pr	Contact			e.aliot@chru-nancy.fr

Overall Officials

Name	Affiliation	Role
Etienne ALIOT, Pr	Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois, France	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Département de Cardiologie, CHU Nancy, Hôpitaux de Brabois	Recruiting	Vandœuvre-lès-Nancy			France

IPD Sharing Statement Module

Plan to Share IPD

Description

Not provided

Types

Not provided

Time Frame

Not provided

Access Criteria

Not provided

URL

Not provided

ID	Term
D001145	Arrhythmias, Cardiac
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D013048	Specimen Handling
D019411	Clinical Laboratory Techniques
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis
D011677	Punctures
D013514	Surgical Procedures, Operative
D008919	Investigative Techniques