Ischemia-Reperfusion InjuryPhase 4NCT00457405
Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?
A Phase 4 study testing dipyridamole in people with Ischemia-Reperfusion Injury and Atherosclerosis, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
This study is performed to determine whether a seven day treatment with dipyridamole (slow release, 200mg twice daily) can induce a protective effect against ischemia-reperfusion injury, after ischemic exercise of the non-dominant forearm in healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Ischemia-Reperfusion Injury, Atherosclerosis
- What is being tested?
- dipyridamole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2007to Mar 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male
- age between 18-50yr.
Who cannot join
- 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 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.
- concomitant medication
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, 6500HB
About this study
This study is performed to determine whether a seven day treatment with dipyridamole (slow release, 200mg twice daily) can induce a protective effect against ischemia-reperfusion injury, after ischemic exercise of the non-dominant forearm in healthy volunteers.
Read the detailed description
Rationale:
Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury (pharmacologic preconditioning).
The purpose of this project is to explore whether a seven day treatment with dipyridamole can reduce ischemia-reperfusion injury in the forearm, in a randomized double blind placebo controlled trial.
Study design:
Randomized double-blind placebo-controlled trial with a cross-over design.
Study population:
Healthy male volunteers, aged 18-50 yr
Intervention:
10 Volunteers will be randomised to receive in a cross-over design either a 7 day treatment with dipyridamole (Persantin retard; 200 mg twice daily) or placebo followed by 10 minutes of ischemic isometric muscle contraction of the non-dominant forearm and upon reperfusion infusion of radiolabeled Annexin A5 (Annexin scintigraphy).
Main study parameters/endpoints:
Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
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.
- Conditions
- Ischemia-Reperfusion Injury, Atherosclerosis
- Being tested
- dipyridamole
- Keywords
- ischemia-reperfusion injury, atherosclerosis, dipyridamole, annexin A5 targeting
- Medical subject headings
- Reperfusion Injury, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dipyridamoleDrug
Also called persantin
dipyridamole 200mg twice daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | first 7 day treatment with dipyridamol and at least two weeks later 7 day treatment with placebo Receives: Drug: dipyridamole |
| 2 | Active comparator | first 7 day treatment with placebo and at least two weeks later 7 day treatment with atorvastatin Receives: Drug: dipyridamole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.
Measured: 60 and 240 minutes after reperfusion
Secondary outcomes (3)
Plasma dipyridamole concentration
Measured: in the morning of day seven of treatment
Workload (duration of exercise and developed force)
Measured: during 10 minutes ischemic exercise
Heart rate (preceded by a 7day treatment of dipyridamol or placebo)
Measured: during 30 minutes at day seven of treatment with dipyridamol and placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2007 (estimated)
- Study startJun 2007
- Primary completionOct 2007
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemia-Reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- G Rongen, MD PhD, Principal investigator, RUNMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00457405
- Sponsor's protocol ID
- dipy003
- Status last verified
- Apr 2008
- First submitted
- 4 Apr 2007
- Last updated
- 15 Apr 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 16003293
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?
- ClinicalTrials.gov ID
- NCT00457405
- Acronym / sponsor ID
- dipy003
- Conditions
- Ischemia-Reperfusion Injury, Atherosclerosis
- Keywords
- ischemia-reperfusion injury, atherosclerosis, dipyridamole, annexin A5 targeting
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Oct 2007 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 6 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is performed to determine whether a seven day treatment with dipyridamole (slow release, 200mg twice daily) can induce a protective effect against ischemia-reperfusion injury, after ischemic exercise of the non-dominant forearm in healthy volunteers.
Detailed description
Rationale:
Dipyridamole increases the endogenous adenosine level by inhibition of the nucleoside transporter (ENT-1). Activation of the adenosine receptor protects against ischemia-reperfusion injury (pharmacologic preconditioning).
The purpose of this project is to explore whether a seven day treatment with dipyridamole can reduce ischemia-reperfusion injury in the forearm, in a randomized double blind placebo controlled trial.
Study design:
Randomized double-blind placebo-controlled trial with a cross-over design.
Study population:
Healthy male volunteers, aged 18-50 yr
Intervention:
10 Volunteers will be randomised to receive in a cross-over design either a 7 day treatment with dipyridamole (Persantin retard; 200 mg twice daily) or placebo followed by 10 minutes of ischemic isometric muscle contraction of the non-dominant forearm and upon reperfusion infusion of radiolabeled Annexin A5 (Annexin scintigraphy).
Main study parameters/endpoints:
Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: dipyridamolefirst 7 day treatment with dipyridamol and at least two weeks later 7 day treatment with placebo |
| 2 | Active comparator | Drug: dipyridamolefirst 7 day treatment with placebo and at least two weeks later 7 day treatment with atorvastatin |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Male
- age between 18-50yr.
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dipyridamoleAlso: persantindipyridamole 200mg twice daily | Drug | 1, 2 |
Primary outcome
Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion.
Time frame: 60 and 240 minutes after reperfusion
3 secondary outcomes
Plasma dipyridamole concentration
Time frame: in the morning of day seven of treatment
Workload (duration of exercise and developed force)
Time frame: during 10 minutes ischemic exercise
Heart rate (preceded by a 7day treatment of dipyridamol or placebo)
Time frame: during 30 minutes at day seven of treatment with dipyridamol and placebo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2008.
- Background: PubMed 16003293Riksen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
G Rongen, MD PhD principal investigator
RUNMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dipyridamole in people with Ischemia-Reperfusion Injury and Atherosclerosis, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage difference in radioactivity (counts/pixel) between experimental and control thenar muscle at 60 and 240 minutes after reperfusion. (time frame: 60 and 240 minutes after reperfusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00457405, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2008.