AtherosclerosisPhase 4NCT00851175
Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?
A Phase 4 study testing rosuvastatin and caffeine in people with Atherosclerosis and Cardiovascular Disease, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Statins form a class of drugs that is widely prescribed for hypercholesterolaemia, specifically to reduce the risk on atherosclerosis by lowering LDL-cholesterol. Next to the effect for which the drug was originally developed, it became obvious that statins have several other beneficial effects. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis, Cardiovascular Disease
- What is being tested?
- rosuvastatin and caffeine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2009to Sep 2009
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-50
- Written informed consent
Who cannot join
- History of any cardiovascular disease
- Hypertension (in supine position: systole >140 mmHg, diastole >90 mmHg)
- Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11.0 mmol/L)
- Hyperlipidemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/L)
- Alanine amino transferase >90 U/L
- Creatin kinase >440 U/L
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- Raised rhabdomyolysis risk (GFR <80 ml/min and/or overt clinical signs of hypothyroidism and/or myopathy in family history
- Alcohol abuse
- Concommitant chronic use of medication
- Participation to any drug-investigation during the previous 60 days as checked with VIP check
Trial locations and contacts
1 site in 1 country.
About this study
Rationale:
Statins form a class of drugs that is widely prescribed for hypercholesterolaemia, specifically to reduce the risk on atherosclerosis by lowering LDL-cholesterol. Next to the effect for which the drug was originally developed, it became obvious that statins have several other beneficial effects. Such pleiotropic effects include the activation of ecto-5'-nucleotidase which can increase endogenous adenosine production (by dephosphorylation adenosine monophosphate into adenosine) and subsequently cause vasodilation. A recent study of Meijer et al (not yet published) showed that rosuvastatin significantly augments vasodilation after a brief period of ischemia (post occlusive reactive hyperaemia). However, it is not yet verified whether this increase in post occlusive reactive hyperaemia is truly caused by a rise of extracellular adenosine and subsequent adenosine receptor stimulation. In this study, the mechanism by which rosuvastatin augments post occlusive reactive hyperaemia will be investigated by blocking adenosine receptors with caffeine, a competitive A1 and A2 adenosine receptor antagonist. Caffeine is a substance that can be safely used in normal concentrations to block the adenosine receptor.
Read more
Hypothesis:
The augmenting effect of rosuvastatin on PORH is caused by an increase of extracellular adenosine formation and this effect can be diminished by blocking the adenosine receptor using caffeine.
Objective:
To study the influence of caffeine on post occlusive reactive hyperaemia before and after 7 days treatment with rosuvastatin.
Study design:
Open label cross-over design Study population: Healthy volunteers, 18-50 years of age
Intervention:
Eight volunteers will receive a 7 day treatment with rosuvastatin 20 mg daily before and after rosuvastatin treatment caffeine will be administrated intra-arterially.
Main study parameters/endpoints:
Forearm blood flow (FBF) will be measured as an indicator for post occlusive reactive hyperaemia (PORH).
- Conditions
- Atherosclerosis, Cardiovascular Disease
- Being tested
- rosuvastatin, caffeine
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosuvastatinDrug
7 day treatment with rosuvastatin 1dd 20mg
caffeineDrug
intra-arterial (brachial artery of non dominant arm) administration of caffeine(90 ug/min/100ml forearm volume)for approximately 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | forearm bloodflow after 2,3, and 5 minutes of forearm ischemia |
| 2 | Active comparator | forearm bloodflow after 2,3, and 5 minutes of forearm ischemia with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm Receives: Drug: caffeine |
| 3 | Experimental | forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg Receives: Drug: rosuvastatin |
| 4 | Active comparator | forearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm Receives: Drug: rosuvastatin; Drug: caffeine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia
Measured: before and after 7 day treament with rosuvastatin, with and without concommitant intra-arterial treatment with caffeine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2009 (estimated)
- Study startMar 2009
- Primary completionAug 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies 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
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
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
- NCT00851175
- Sponsor's protocol ID
- rosucaff2
- Status last verified
- Mar 2009
- First submitted
- 24 Feb 2009
- Last updated
- 1 Oct 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Meijer P, Wouters CW, van den Broek PH, Scheffer GJ, Riksen NP, Smits P, Rongen GA. Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation. Br J Pharmacol. 2008 Mar;153(6):1169-76. doi: 10.1038/bjp.2008.10. Epub 2008 Feb 11.
PubMed 18264130Bijlstra PJ, den Arend JA, Lutterman JA, Russel FG, Thien T, Smits P. Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans. Diabetologia. 1996 Dec;39(12):1562-8. doi: 10.1007/s001250050615.
PubMed 8960843
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is Augmentation of PORH by Rosuvastatin Adenosine-receptor Mediated?
- ClinicalTrials.gov ID
- NCT00851175
- Acronym / sponsor ID
- rosucaff2
- Conditions
- Atherosclerosis, Cardiovascular Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Aug 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 25 Feb 2009 (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.
Rationale:
Statins form a class of drugs that is widely prescribed for hypercholesterolaemia, specifically to reduce the risk on atherosclerosis by lowering LDL-cholesterol. Next to the effect for which the drug was originally developed, it became obvious that statins have several other beneficial effects. Such pleiotropic effects include the activation of ecto-5'-nucleotidase which can increase endogenous adenosine production (by dephosphorylation adenosine monophosphate into adenosine) and subsequently cause vasodilation. A recent study of Meijer et al (not yet published) showed that rosuvastatin significantly augments vasodilation after a brief period of ischemia (post occlusive reactive hyperaemia). However, it is not yet verified whether this increase in post occlusive reactive hyperaemia is truly caused by a rise of extracellular adenosine and subsequent adenosine receptor stimulation. In this study, the mechanism by which rosuvastatin augments post occlusive reactive hyperaemia will be investigated by blocking adenosine receptors with caffeine, a competitive A1 and A2 adenosine receptor antagonist. Caffeine is a substance that can be safely used in normal concentrations to block the adenosine receptor.
Hypothesis:
The augmenting effect of rosuvastatin on PORH is caused by an increase of extracellular adenosine formation and this effect can be diminished by blocking the adenosine receptor using caffeine.
Objective:
To study the influence of caffeine on post occlusive reactive hyperaemia before and after 7 days treatment with rosuvastatin.
Study design:
Open label cross-over design Study population: Healthy volunteers, 18-50 years of age
Intervention:
Eight volunteers will receive a 7 day treatment with rosuvastatin 20 mg daily before and after rosuvastatin treatment caffeine will be administrated intra-arterially.
Main study parameters/endpoints:
Forearm blood flow (FBF) will be measured as an indicator for post occlusive reactive hyperaemia (PORH).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –forearm bloodflow after 2,3, and 5 minutes of forearm ischemia |
| 2 | Active comparator | Drug: caffeineforearm bloodflow after 2,3, and 5 minutes of forearm ischemia with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm |
| 3 | Experimental | Drug: rosuvastatinforearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg |
| 4 | Active comparator | Drug: rosuvastatin, Drug: caffeineforearm bloodflow after 2,3, and 5 minutes of forearm ischemia after 7 days oral treatment with rosuvastatin 1dd 20mg with concommitant administration of caffeine (90 ug/min/100ml forearm volume) into the brachial artery of the experimental (=non dominant) arm |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age 18-50
- Written informed consent
Key exclusion criteria (10 listed)
- History of any cardiovascular disease
- Hypertension (in supine position: systole >140 mmHg, diastole >90 mmHg)
- Diabetes Mellitus (fasting glucose >7.0 mmol/L or random glucose >11.0 mmol/L)
- Hyperlipidemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/L)
- Alanine amino transferase >90 U/L
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 |
|---|---|---|
| rosuvastatin7 day treatment with rosuvastatin 1dd 20mg | Drug | 3, 4 |
| caffeineintra-arterial (brachial artery of non dominant arm) administration of caffeine(90 ug/min/100ml forearm volume)for approximately 60 minutes | Drug | 2, 4 |
Primary outcome
Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia
Time frame: before and after 7 day treament with rosuvastatin, with and without concommitant intra-arterial treatment with caffeine
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 1 Oct 2009.
- Background: PubMed 18264130Meijer P, Wouters CW, van den Broek PH, Scheffer GJ, Riksen NP, Smits P, Rongen GA. Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation. Br J Pharmacol. 2008 Mar;153(6):1169-76. doi: 10.1038/bjp.2008.10. Epub 2008 Feb 11.
- Background: PubMed 8960843Bijlstra PJ, den Arend JA, Lutterman JA, Russel FG, Thien T, Smits P. Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans. Diabetologia. 1996 Dec;39(12):1562-8. doi: 10.1007/s001250050615.
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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 rosuvastatin and caffeine in people with Atherosclerosis and Cardiovascular Disease, 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 10 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 1 Oct 2009. 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?
Forearm blood flow (FBF)after 2, 5, and 13 minutes of forearm ischemia (time frame: before and after 7 day treament with rosuvastatin, with and without concommitant intra-arterial treatment with caffeine). 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 NCT00851175, which also lists 2 linked publications.
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 1 Oct 2009.