Ticagrelor and Adenosine

Study Overview
=================
Brief Summary
-----------------
Preclinical studies have shown that the P2Y12 receptor antagonist ticagrelor can increase the extracellular concentration of the endogenous nucleoside adenosine by inhibiting the cellular uptake of adenosine via the equilibrative nucleoside transporter (ENT). This mechanism can contribute to the beneficial effects and to the side effects (dyspnea) of ticagrelor in patients with an acute myocardial infarction. In the current research proposal, we aim to investigate whether ticagrelor increases adenosine receptor stimulation in humans in vivo by ENT inhibition.

Official Title
-----------------
The Effect of Ticagrelor on the Adenosine System

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Ticagrelor 180 mg single dose
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male sex Age 18-40 years Healthy Written informed consent Exclusion Criteria: Smoking Hypertension (Blood pressure >140 mmHg and/or >90 mmHg - SBP/DBP-) Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random > 11.0 mmol/L) History of any cardiovascular disease History of chronic obstructive pulmonary disease (COPD) or asthma Bleeding tendency Concomitant use of medication Renal dysfunction (MDRD < 60 ml/min) Liver enzyme abnormalities (ALAT > twice upper limit of normality) Thrombocytopenia (<150*109/ml) Second/third degree AV-block on electrocardiography

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ticagrelor 180 mg single dose<br>Ticagrelor 180 mg single dose | Drug: Ticagrelor 180 mg single dose<br> <br> |
| Placebo Comparator: Placebo<br>Placebo single dose | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forearm blood flow response | Forearm blood flow response to the intrabrachial administration of incremental dosages of adenosine, after treatment with ticagrelor compared to placebo. The forearm blood flow will be measured by plethysmography. | 2 hours after intake of ticagrelor/placebo | 
| Forearm blood flow response | Directly after 2 and 5 minutes of forearm ischemia.The forearm blood flow will be measured by plethysmography. | Directly after 2 and 5 minutes of forearm ischemia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forearm blood flow respons | Forearm blood flow response to the intrabrachial administration of incremental dosages of dipyridamole, after treatment with ticagrelor compared to placebo. The forearm blood flow will be measured by plethysmography | Directly after administration of dipyridamole | 
| ex-vivo adenosine uptake in isolated erythrocytes | To study whether ticagrelor inhibits the ex-vivo adenosine uptake in isolated erythrocytes | 2 hours after intake of studymedication | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endothelial function, Adenosine receptor stimulation