Genetic Determinants of Cardiovascular Response to Coffee Drinking

Study Overview
=================
Brief Summary
-----------------
Cardiovascular and neuropsychologic effects of coffee are still debated. The precise mechanism underlying the actions of caffeine on the cardiovascular and neuropsychologic systems is incompletely understood and a considerable variability in the response to coffee drinking was observed, in part ascribable to a genetic trait. The aim of the study is to evaluate acute cardiovascular and neuropsychologic effects of coffee and explore whether such effects are influenced by the genetic asset of caffeine metabolism (by a polymorphisms of cytochrome P450 1A2), adenosine metabolism (by polymorphisms of adenosine receptor and adenosine monophosphate deaminase) or catecholamine receptors (by polymorphisms of adrenergic receptors).

Detailed Description
-----------------
Coffee is among the most widely consumed beverages worldwide. Despite the relationship between coffee consumption and the incidence of cardiovascular disease has been studied extensively, the effects of this drink on the cardiovascular apparatus and its role as a risk factor for coronary heart disease are still debated. Moreover, the effect of coffee on attention, sleep changes, anxiety and panic disorders was studied but a great variability was observed. Many of the known or suspected cardiovascular and neuropsychologic effects of coffee have been attributed to caffeine. The main mechanism of action of caffeine is to antagonize adenosine receptors; a secondary effect is the inhibition of phosphodiesterases, with the subsequent accumulation of cyclic adenosine monophosphate and a intensification of the effects of catecholamines. It is also well known that there is a considerable variability in the cardiovascular and neuropsychologic response to coffee drinking, explaining the inconsistency between different effects observed in the various studies. This variability may have a genetic basis. The aim of the study is to evaluate acute cardiovascular and neuropsychologic effects of coffee and explore whether such effects are influenced by the genetic asset of caffeine metabolism (by a polymorphisms of cytochrome P450 1A2), adenosine metabolism (by polymorphisms of adenosine receptor and adenosine monophosphate deaminase) or catecholamine receptors (by polymorphisms of adrenergic receptors).

Official Title
-----------------
Genetic Determinants of Cardiovascular Response to Coffee Drinking

Conditions
-----------------
Caffeine

Intervention / Treatment
-----------------
* Dietary Supplement: Coffee
* Dietary Supplement: Decaffeinated coffee


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 40 years Males (to avoid variation due to female hormonal cycle) No known active ongoing disease (apparent good health) Non-smokers (to avoid contributory effects of nicotine or other tobacco alkaloids to caffeine effects or tolerance) Average coffee intake (not less than one cup/day and not greater than three cups/day) Exclusion Criteria: Treatment with any drug with known activity on the adrenergic system Hypertension Therapy with sympathomimetic drugs, theophylline, alpha- or beta-blockers, any antihypertensive therapy Body mass index (BMI) > 30 kg/m2 (obesity) BMI < 18.5 kg/m2

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Coffee<br> | Dietary Supplement: Coffee<br>* 40 mL dose of a decaffeinated preparation spiked with the addition of caffeine, at a dose of 3 mg/kg<br>|
| Active Comparator: Decaffeinated coffee<br> | Dietary Supplement: Decaffeinated coffee<br>* 40 mL dose of decaffeinated coffee<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in platelet aggregation | Light transmission aggregometry (LTA) induced by ADP and apinephrine. Platelet function analyzer (PFA) by collagen-ADP and collagen-epinephrine cartridges. | From baseline to 30 minutes and 2 hours after coffee or decaffeinated alternatively | 
| Change in cognitive tasks measures | Low intensity task of focused attention and choice reaction times (Categorical Search Task). More demanding response interference tasks (Letter Flanker Task). Classic interference task (Stroop Test). | From 30 minutes until 2 hours after coffee or decaffeinated alternatively | 
| Change in blood pressure |  | From baseline until 2 hours after coffee or decaffeinated alternatively | 
| Change in heart rate |  | From baseline until 2 hours after coffee or decaffeinated alternatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma caffeine concentration |  | From baseline to 30 minutes and 2 hours after coffee or decaffeinated alternatively | 
| Change in plasma adrenaline and noradrenaline concentration |  | From baseline to 30 minutes and 2 hours after coffee or decaffeinated alternatively | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coffee, caffeine, blood pressure, nutrigenetics, gene polymorphisms, Acute Cardiovascular and Neuropsychologic Effects