Clinical trial NCT02580149: The Effect of Ticagrelor or Clopidogrel on Endothelial Function During Acute and Chronic Treatment
Official title: The Effect of an Acute Dose of Ticagrelor or Clopidogrel and of Treatment for 14 Days on Ischemia-reperfusion Induced Endothelial Dysfunction of the Forearm Vasculature in Healthy Male Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ischemia
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2015-10-20
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Acetylcholin (ACh) induced vasodilatation
timeFrame: Change of the AUC before and 10 min after forearm ischemia
Secondary outcomes:
measure: Area under the curve (AUC) of Forearm blood flow (FBF) measurements of Glyceroltrinitrate (GTN) induced vasodilatation
timeFrame: Change of AUC before and 10 min after forearm ischemia
measure: (Expected) Peak plasma concentration of ticagrelor or clopidogrel
timeFrame: 2.5 h after IMP intake
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Clinical Pharmacology
Study officials:
affiliation: Department of Clinical Pharmacology, Medical University of Vienna
name: Michael Wolzt, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: