Ischemia
Conditions
Brief summary
To investigate if treatment with ticagrelor can mitigate the transient loss of endothelium-dependent vasodilatation of the resistance vasculature following a short period of ischemia, compared with clopidogrel at standard clinical doses. The effect of ticagrelor or clopidogrel will be studied after a loading dose and after a two weeks period of regular intake on FBF in response to the vasodilators acetylcholine or nitroglycerin before and 10 min after a 20 min forearm ischemia, respectively.
Detailed description
Ischemia-reperfusion (IR) causes tissue injury. Preclinical animal data suggest that ticagrelor but not clopidogrel protects against IR injury due to inhibition of cellular adenosine uptake and NO-synthase stimulation. It is unclear if this action is part of the beneficial clinical effect of ticagrelor in patients with a history of acute coronary syndrome. The preventive action of ticagrelor on IR injury may also be of interest for the peripheral vasculature, where IR injury is known to result in endothelial dysfunction. This study aims to investigate if treatment with ticagrelor can mitigate the transient loss of endothelium-dependent vasodilatation of the resistance vasculature following a short period of ischemia, compared with clopidogrel at standard clinical doses. We will study the effect of ticagrelor or clopidogrel after a loading dose and after a two weeks period of regular intake on forearm blood flow (FBF) reactivity in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (GTN; endothelium-independent vasodilator) before and 10 min after a 20 min forearm ischemia, respectively
Interventions
DRUGTicagrelor
Subjects will receive an oral loading dose of 180 mg ticagrelor on study day 1 followed by a maintenance dose of 90 mg twice daily for 14 days (until study day 15).
DRUGClopidogrel
Subjects will receive a loading dose of 600 mg clopidogrel on the first study day followed by a maintenance dose of 75 mg once daily for 14 days
Sponsors
Michael Wolzt, Prof. MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects; 18 - 40 years of age * Body mass index between 18 and 27 kg/m2 * Written informed consent * Normal findings in medical & bleeding history * Non-smoking
Exclusion criteria
* Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration * Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease) * Known disorders with increased bleeding risk (e.g. peridontosis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer) * Known sensitivity to common causes of bleeding (e.g. nasal) * History of thromboembolism * History of occlusive vascular diseases * History of vascular anomalies * Impaired liver function (AST, ALT, gGT, bilirubin \>2 x ULN) * Impaired renal function (serum creatinine \> 1.3 mg/dl) * Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis * HIV-1/2-Ab, HbsAg or HCV-Ab positive serology * Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg * Known allergy against any test agent under study * Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol * Participation in another clinical trial during the preceding 3 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholin (ACh) induced vasodilatation | Change of the AUC before and 10 min after forearm ischemia | To test the effect of ticagrelor or clopidogrel on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceroltrinitrate (GTN) induced vasodilatation | Change of AUC before and 10 min after forearm ischemia | To test the effect of ticagrelor or clopidogrel on GTN-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia. |
| (Expected) Peak plasma concentration of ticagrelor or clopidogrel | 2.5 h after IMP intake | — |
Countries
Austria
Outcome results
None listed