The purpose of this project is to explore whether a short treatment with dipyridamole (2.5 days; i.e. 5 capsules) can reduce ischemia-reperfusion injury in the forearm.
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage difference in radioactivity (counts/pixel) between experimental and
control thenar muscle at 60 and 240 minutes after reperfusion.
Secondary outcome
nvt
Background summary
A 7 day treatment of dipyridamole has been proven to reduce targeting of
Annexin A5 in responses to ischemic exercise, indicating protection against
ischemia-reperfusion injury in humans (pharmacological preconditioning).
Dipyridamole increases the endogenous adenosine level by inhibition of the
nucleoside transporter (ENT-1). Activation of the adenosine receptor protects
against ischemia-reperfusion injury. However it is uncertain whether a
treatment with dipyridamole of the duration of at least 7 days is necessary to
induce protection against ischemia-reperfusion injury. For clinical application
of dipyridamole induced protection against ischemia reperfusion injury, in for
example the setting of an elective PTCA, a treatment duration of maximum 2 to 3
days could be implementable.
Study objective
The purpose of this project is to explore whether a short treatment with
dipyridamole (2.5 days; i.e. 5 capsules) can reduce ischemia-reperfusion injury
in the forearm.
Study design
Randomised cross-over design, single blinded (observer main outcome parameter)
Intervention
10 Volunteers will be randomised to receive in a cross-over design a two and a
half day (5 capsules) treatment with dipyridamole (Persantin retard; 200 mg
twice daily) followed by 10 minutes of ischemic isometric muscle contraction of
the non-dominant forearm and upon reperfusion infusion of radiolabeled Annexin
A5 (Annexin scintigraphy) and Annexin scintigraphy alone.
Study burden and risks
This study will be executed at the Clinical Research Centre Nijmegen under
close medical supervision. Treatment with dipyridamole is not expected to harm
the volunteers. During the first days of treatment with dipyridamole, a
headache may occur. Ischemic hand gripping will temporarily result in pain in
the forearm. This is completely reversible upon reperfusion. Administration of
radiolabeled Annexin A5 results in an effective dose of less than 5 mSv, well
within the range of accepted exposure to radioactivity for human research.
Participation in this research does not interfere with possible diagnostic or
therapeutic procedures with X-rays of radioactivity in the future.
Occurrence of an allergic reaction is theoretically possible upon
administration of Annexin A5, however there have been no allergic reactions
reported in all volunteers exposed to Annexin A5.
The volunteers will not benefit directly from participating in this study.
postbus 9101
6500 HB Nijmegen
Nederland
postbus 9101
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
male
age 18-50 years
Exclusion criteria
-cardiovascular disease
-hypertension (systole > 140 mmHg, diastole > 90 mmHg)
-hypercholesterolemia (fasting total cholesterol > 5.5 mmol/l or not fasting total cholesterol > 6.5mmol/L)
-diabetes mellitus (fasting glucose > 7.0 mmol/L or random glucose > 11.0 mmol/L)
-asthma (recurrent episodes of dyspnea and wheezing, or usage of prescribed inhalation medication: i.e. corticosteroids or B2-agonists)
-participation in any clinical drug trial during the last 60 days prior to this study.
-administration of any radioactivity for research purposes during the last 5 years prior to this study.
-concomittant medication
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001909-26-NL |
| CCMO | NL17415.091.07 |