Explore 4 week post-treatment effect of seven day administration of dipyridamole on nucleoside transport inhibition.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Comparison of nucleoside uptake inhibition before, during (day 7), and after
(day 14, 21, 28, and 35) treatment with dipyridamole between actively treated
an control individuals at 35 days after start of the study (28 days after
cessation of treatment in actively treated subjects).
Secondary outcome
plasma and whole blood dipyridamole concentration
Background summary
Preclinical evidence and a couple of human in-vivo studies have confirmed that
nucleoside transport inhibitors such as dipyridamole enhance tolerance against
IR-injury. Recently we have shown a protective effect of one week oral
treatment with dipyridamole (200 mg, slow release, twice daily) in a forearm
model of ischemia-reperfusion injury using Annexin A5 targeting as a marker of
injury. In a separate follow-up randomised double-blind placebo-controlled
cross-over experiment we observed a protection by dipyridamole that persisted
even 4 weeks after cessation of dipyridamole treatment. This study aims to
explore a potential explanation for this intriguing observation.
We hypothesize that dipyridamole accumulates in cell membranes and inhibits the
nucleoside transporter in these membranes for a prolonged time even after
plasma dipyridamole levels are below limits of detection.
Study objective
Explore 4 week post-treatment effect of seven day administration of
dipyridamole on nucleoside transport inhibition.
Study design
placebo-controlled trial with open-label design.
Intervention
treatment with either dipyridamole slow release 200 mg twice daily or no
treatment during 7 days with subsequent 4 week follow-up after cessation of the
treatment.
Study burden and risks
Screening: medical history, physical examination, ECG, capillary glucose
measurement.
Burden: 6x venous blood collection (120 ml in total)
Risks: side effects of dipyridamole treatment (headache and dyspepsia are most
common), all reversible upon cessation of treatment.
P.O. Box 9101
6500 HB Nijmegen
NL
P.O. Box 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers
Age 18-50
Written informed consent
Exclusion criteria
Smoking
History of any cardiovascular disease
Asthma
Hypertension (in supine position: systole>140 mm Hg, diastole>90 mmHg)
Diabetes mellitus (fasting glucose >7.0 mmol/L or random glucose>11.0 mmol/L)
Concomitant use of medication
Alcohol or drug abuse
Women without appropriate anticonception
Participation to any drug-investigation during the previous 60 days as checked with VIP check
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 | EUCTR2010-018338-39-NL |
| CCMO | NL31291.091.10 |