"Potential Effect of Acute and Chronic Caffeine Administration on Platelet Reactivity in Patient With Coronary Artery Disease on Dual Antiplatelet Therapy"

NCT ID: NCT02054988

Last Updated: 2015-06-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-06-30

Brief Summary

Prasugrel is a potent thienopyridine antiplatelet agent that selectively and irreversibly inhibits ADP-induced platelet aggregation mediated by the P2Y12 receptor. Prasugrel is a prodrug that must first undergo biotransformation to its active metabolite via cytochrome P450-mediated hepatic metabolism (CYP1A2). Clopidogrel is currently administered to several million patients especially after coronary stenting. Clopidogrel has been shown to reduce cardiovascular complications in patients with acute coronary syndromes and patients who have undergone coronary stenting. The mechanism of action of clopidogrel's active metabolite involves inhibition of the purinergic adenosine diphosphate (ADP) receptor P2Y12 on the platelet membrane. Blockade of this receptor prevents uncoupling of the associated Gi2 protein which ultimately leads to increased platelet cyclic AMP (cAMP) formation.3 Cyclic AMP is a key signaling molecule in inhibiting platelet aggregation, but its intracellular levels are affected by several other commonly used compounds. For instance, methylxanthines, such as caffeine, theophylline, and theobromine (an ingredient of chocolate), all cause elevation of intracellular cAMP levels by inhibiting adenosine receptors (types A1 and A2) on the platelet membrane. The effect of caffeine consumption on platelet reactivity depends on the caffeine dose and duration of administration. Chronic caffeine consumption (≥7 days) appears to be associated with inhibition of platelet aggregation, probably through upregulation of adenosine receptors.The aim of this study was to examine the effect of acute caffeine consumption, at a dose equivalent to commercial coffee drinks, on the antiplatelet effect of clopidogrel and prasugrel, in patients with coronary artery disease (CAD).

Platelet function will be evaluated using a validated method: the VerifyNow System (Accumetrics Inc., San Diego, CA), which is a point-of-care turbidimetry-based optical detection system that measures platelet-induced aggregation.

Detailed Description

Prasugrel is a potent thienopyridine antiplatelet agent that selectively and irreversibly inhibits ADP-induced platelet aggregation mediated by the P2Y12 receptor. Prasugrel is a prodrug that must first undergo biotransformation to its active metabolite via cytochrome P450-mediated hepatic metabolism (CYP1A2). Clopidogrel is currently administered to several million patients especially after coronary stenting. Clopidogrel has been shown to reduce cardiovascular complications in patients with acute coronary syndromes and patients who have undergone coronary stenting. The mechanism of action of clopidogrel's active metabolite involves inhibition of the purinergic adenosine diphosphate (ADP) receptor P2Y12 on the platelet membrane. Blockade of this receptor prevents uncoupling of the associated Gi2 protein which ultimately leads to increased platelet cyclic AMP (cAMP) formation.3 Cyclic AMP is a key signaling molecule in inhibiting platelet aggregation, but its intracellular levels are affected by several other commonly used compounds. For instance, methylxanthines, such as caffeine, theophylline, and theobromine (an ingredient of chocolate), all cause elevation of intracellular cAMP levels by inhibiting adenosine receptors (types A1 and A2) on the platelet membrane. The effect of caffeine consumption on platelet reactivity depends on the caffeine dose and duration of administration. Chronic caffeine consumption (≥7 days) appears to be associated with inhibition of platelet aggregation, probably through upregulation of adenosine receptors. The effect of acute caffeine administration on platelet function is less clear. Different studies have shown either an increase, decrease, or no change in platelet reactivity after acute caffeine administration. The aim of this study was to examine the effect of acute caffeine consumption, at a dose equivalent to commercial coffee drinks, on the antiplatelet effect of clopidogrel and prasugrel, in patients with coronary artery disease (CAD).

Platelet function will be evaluated using a validated method: the VerifyNow System (Accumetrics Inc., San Diego, CA), which is a point-of-care turbidimetry-based optical detection system that measures platelet-induced aggregation. Platelet function will be measured with the VerifyNow P2Y12 test at baseline, (after 5 day wash-out period to avoid any carryover effect ) and after 10 days of taking caffeine.

Conditions

CORONARY ARTERY DISEASE

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: QUADRUPLE

Study Groups

caffeine

three cups of coffee will be administered for 10 days (on chronic phase) and two cups of coffee will be consecutively administered for "acute" evaluation.

Group Type: EXPERIMENTAL

caffeine

Intervention Type: OTHER

After 5 day coffee wash-out period, patients were randomly assigned to caffeine for 10 days. At baseline: 2 cups of coffee consecutively after 5 hour by clopidogrel or prasugrel intake. Afterwards, 3 cups of coffee daily for 10 days.

Platelet reactivity (expressed as P2Y(12) reaction units (PRU) by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) was measured at baseline and after 10-days of coffee intake.

not caffeine

not caffeine will be administered for the duration of the study

Group Type: ACTIVE_COMPARATOR

not caffeine

Intervention Type: OTHER

evaluate the platelet reactivity after 10 days of no caffeine intake

Interventions

caffeine

After 5 day coffee wash-out period, patients were randomly assigned to caffeine for 10 days. At baseline: 2 cups of coffee consecutively after 5 hour by clopidogrel or prasugrel intake. Afterwards, 3 cups of coffee daily for 10 days.

Platelet reactivity (expressed as P2Y(12) reaction units (PRU) by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) was measured at baseline and after 10-days of coffee intake.

Intervention Type: OTHER

not caffeine

evaluate the platelet reactivity after 10 days of no caffeine intake

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. All consecutive patients undergone PTCA

2. Patients on dual antiplatelet therapy with ASA and clopidogrel or prasugrel or ticagrelor.

Exclusion Criteria

1. People unable to understand and willing to sign the informed consent form;

2. Smokers

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Polacco Marina

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marina MD Polacco

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

Locations

Sapienza University of Rome

Rome, Lazio, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Marina Polacco MD

Role: CONTACT

polamari@libero.it

3204093510

Facility Contacts

marina polacco MD

Role: primary

Other Identifiers

PM3110

Identifier Type: -

Identifier Source: org_study_id