Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
Primary Purpose
Cardiovascular Disease, Ischemia-Reperfusion Injury
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Dipyridamole
caffeine
Sponsored by
About this trial
This is an interventional treatment trial for Cardiovascular Disease focused on measuring ischemia-reperfusion injury, adenosine, dipyridamole, caffeine
Eligibility Criteria
Inclusion Criteria:
- Male
- Age between 18-50yr.
Exclusion Criteria:
- cardiovascular disease
- hypertension (systole > 140 mmHg, diastole > 90 mmHg)
- hypercholesterolemia (random total cholesterol > 6.5 mmol/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 trial during the last 60 days prior to this study.
- administration of two doses of Annexin A5 (0,1mg; 450MBq) during the last 5 years prior to this study.
Sites / Locations
- Radboud University Nijmegen Medical Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
1
2
Arm Description
dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg
dipyridamol during 7 days and before ischemic exercise placebo
Outcomes
Primary Outcome Measures
Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion
Secondary Outcome Measures
Plasma dipyridamole concentration
ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days)
Workload (duration of exercise and developed force)
Full Information
NCT ID
NCT00430170
First Posted
January 31, 2007
Last Updated
July 28, 2008
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00430170
Brief Title
Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
Official Title
Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
Study Type
Interventional
2. Study Status
Record Verification Date
July 2008
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
April 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Radboud University Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this project is to explore the interaction between caffeine and dipyridamole on ischemia-reperfusion injury in the forearm.
Detailed Description
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. We hypothesize that endogenous adenosine mediates the protective effect of dipyridamole against ischemia-reperfusion injury. Therefore the adenosine receptor antagonist caffeine will reduce the benefit of dipyridamole on forearm ischemia-reperfusion injury.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Disease, Ischemia-Reperfusion Injury
Keywords
ischemia-reperfusion injury, adenosine, dipyridamole, caffeine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
dipyridamol during 7 days and before ischemic exercise caffeine 4mg/kg
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
dipyridamol during 7 days and before ischemic exercise placebo
Intervention Type
Drug
Intervention Name(s)
Dipyridamole
Other Intervention Name(s)
persatin
Intervention Description
Dipyridamole 2x200mg 7day per os
Intervention Type
Drug
Intervention Name(s)
caffeine
Intervention Description
caffeine 4mg/kg iv
Primary Outcome Measure Information:
Title
Percentage difference in Annexin A5 targetting between experimental and control thenar muscle at 60 and 240 minutes after reperfusion
Time Frame
60 and 240 minutes after ischemic exercise
Secondary Outcome Measure Information:
Title
Plasma dipyridamole concentration
Time Frame
at the morning of day 7 of treatment with dipyridamole/placebo
Title
ENT transport activity (before and after treatment with dipyridamole 200mg, twice daily, for seven days)
Time Frame
before start of treatment (dipyridamol/placebo) and in the morning of day 7 of treatment (placebo/dipyridamol)
Title
Workload (duration of exercise and developed force)
Time Frame
during 10 minutes of ischemic exercise
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male
Age between 18-50yr.
Exclusion Criteria:
cardiovascular disease
hypertension (systole > 140 mmHg, diastole > 90 mmHg)
hypercholesterolemia (random total cholesterol > 6.5 mmol/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 trial during the last 60 days prior to this study.
administration of two doses of Annexin A5 (0,1mg; 450MBq) during the last 5 years prior to this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard Rongen, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Centre
City
Nijmegen
ZIP/Postal Code
6500hb
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
16003293
Citation
Riksen NP, Oyen WJ, Ramakers BP, Van den Broek PH, Engbersen R, Boerman OC, Smits P, Rongen GA. Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans. Clin Pharmacol Ther. 2005 Jul;78(1):52-9. doi: 10.1016/j.clpt.2005.03.003.
Results Reference
background
PubMed Identifier
15623546
Citation
Rongen GA, Oyen WJ, Ramakers BP, Riksen NP, Boerman OC, Steinmetz N, Smits P. Annexin A5 scintigraphy of forearm as a novel in vivo model of skeletal muscle preconditioning in humans. Circulation. 2005 Jan 18;111(2):173-8. doi: 10.1161/01.CIR.0000151612.02223.F2. Epub 2004 Dec 27.
Results Reference
background
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Does Caffeine Reduce Dipyridamole-Induced Protection Against Ischemia-Reperfusion Injury?
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