Ticagrelor and Adenosine

Healthy Clinical Trial

Official title:

The Effect of Ticagrelor on the Adenosine System

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01996735
• Other study ID #: NL43379.091.13
• Status: Completed
• Phase: Phase 4
• First received: April 26, 2013
• Last updated: January 9, 2014
• Start date: April 2013
• Est. completion date: December 2013

Study information

• Verified date: February 2013
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Ticagrelor 180 mg single dose

• Placebo

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No