Healthy
Conditions
Keywords
Endothelial function, Adenosine receptor stimulation
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.
Interventions
DRUGTicagrelor 180 mg single dose
DRUGPlacebo
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forearm blood flow response | 2 hours after intake of ticagrelor/placebo | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forearm blood flow respons | Directly after administration of dipyridamole | 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 |
| ex-vivo adenosine uptake in isolated erythrocytes | 2 hours after intake of studymedication | To study whether ticagrelor inhibits the ex-vivo adenosine uptake in isolated erythrocytes |
Countries
Netherlands
Outcome results
None listed