Ischemia Reperfusion InjuryPhase 4NCT00987974
Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
A Phase 4 study testing rosuvastatin, atorvastatin 3 days and rosuvastatin 7 days in people with Ischemia Reperfusion Injury and Endothelial Dysfunction, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Apart from their cholesterol lowering effects, statins have cholesterol-independent pleiotropic actions, such as upregulation of 5'-ectonucleotidase and up-regulation of NO-synthase that may increase tolerance against ischemia-reperfusion injury (IR-injury). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Ischemia Reperfusion Injury, Endothelial Dysfunction
- What is being tested?
- rosuvastatin, atorvastatin 3 days and rosuvastatin 7 days
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2009to Mar 2010
- 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
- Smoking
- 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)
- Hyperlipidaemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/L)
- Alanine amino transferase >90 U/L
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- Creatine kinase >440 U/L
- Raised rhabdomyolysis risk
- GFR <60 ml/min
- Overt clinical signs of hypothyroidism
- Myopathy in family history
- Alcohol abuse
- Concomitant chronic use of medication
- Participation to any drug-investigation during the previous 60 days as checked with VIP check.
- Professional athletes
Trial locations and contacts
1 site in 1 country.
About this study
Rationale:
Apart from their cholesterol lowering effects, statins have cholesterol-independent pleiotropic actions, such as upregulation of 5'-ectonucleotidase and up-regulation of NO-synthase that may increase tolerance against ischemia-reperfusion injury (IR-injury). Several animal studies have shown reduction of IR-injury as a result of statin treatment in both the heart and the kidney. Recently the investigators have shown, using Annexin A5 targeting after voluntary ischemic exercise to assess IR-injury, a protective effect of a 7 day oral rosuvastatin treatment. A three day treatment with atorvastatin however failed to reduce annexin targeting.
Read more
Assessment of the flow mediated dilation of the brachial artery as measure of endothelial (dys)function, is a validated model to research effects of possible protective strategies and perform mechanistic experiments on IR-injury in humans in vivo.
The investigators hypothesize that pretreatment with statins can increase endothelial tolerance against ischemia and reperfusion injury.
Objective:
To study the protective effect of pretreatment (both 3 day and 7 day) with rosuvastatin and atorvastatin on flow mediated dilation after 15 minutes ischemia and 15 minutes reperfusion.
Study design: placebo-controlled randomised double-blind trial
Study population: Healthy volunteers, age 18-50
Intervention: Treatment with either rosuvastatin 20 mg, atorvastatin 80mg or placebo during either 3 or 7 days
Main study parameters: Difference in flow mediated dilation before and after 15 minutes ischemia.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment with rosuvastatin or atorvastatin is not expected to harm the volunteers. Most reported side effects of rosuvastatin and atorvastatin are gastro-intestinal complains and myalgia. The volunteers will not benefit directly from participating in this study.
- Being tested
- rosuvastatin, atorvastatin 3 days, placebo, rosuvastatin 7 days, atorvastatin 7 days
- Keywords
- ischemia reperfusion injury, endothelial dysfunction, statins, rosuvastatin, atorvastatin, placebo, ecto-5'-nucleotidase, flow mediated dilation
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosuvastatinDrug
Also called crestor
rosuvastatin 20 mg/day for 3 days.
atorvastatin 3 daysDrug
Also called lipitor
atorvastatin 80 mg/day for 3 days.
placeboDrug
placebo for 3 days.
rosuvastatin 7 daysDrug
Also called crestor
rosuvastatin 20 mg/day for 7 days
atorvastatin 7 daysDrug
Also called lipitor
atorvastatin 80 mg/day for 7 days.
placebo 7 daysDrug
placebo 7 days
| Study group | Role | What they receive |
|---|---|---|
| rosuvastatin 3days | Experimental | 8 Subjects will use rosuvastatin 20 mg/day for 3 days Receives: Drug: rosuvastatin |
| atorvastatin 3 days | Active comparator | 8 Subjects will use atorvastatin 80 mg/day for 3 days.pj Receives: Drug: atorvastatin 3 days |
| placebo 3days | Placebo comparator | 8 Subjects will use placebo for 3 days. Receives: Drug: placebo |
| rosuvastatin 7 days | Experimental | 8 Subjects will use rosuvastatin 20 mg/day for 7 days. Receives: Drug: rosuvastatin 7 days |
| atorvastatin 7 days | Active comparator | 8 Subjects will use atorvastatin 80 mg/day for 7 days. Receives: Drug: atorvastatin 7 days |
| placebo 7 days | Placebo comparator | 8 Subjects will use placebo for 7 days. Receives: Drug: placebo 7 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in flow mediated dilation before and after 15 minutes ischemia
Measured: 30 minutes
Secondary outcomes (1)
Ecto-5'-nucleotidase activity and lipid profile after statin therapy
Measured: 3-7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionFeb 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987974
- Sponsor's protocol ID
- FMD01
- Status last verified
- Apr 2001
- First submitted
- 30 Sep 2009
- Last updated
- 28 Apr 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Meijer P, Oyen WJ, Dekker D, van den Broek PH, Wouters CW, Boerman OC, Scheffer GJ, Smits P, Rongen GA. Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):963-8. doi: 10.1161/ATVBAHA.108.179622. Epub 2009 Apr 9.
PubMed 19359665Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.
PubMed 11273988Wouters CW, Wever KE, Bronckers I, Hopman MT, Smits P, Thijssen DH, Rongen GA. Short-term statin treatment does not prevent ischemia and reperfusion-induced endothelial dysfunction in humans. J Cardiovasc Pharmacol. 2012 Jan;59(1):22-8. doi: 10.1097/FJC.0b013e318232b1a4.
PubMed 21885990
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Term Statin Treatment and Endothelial Dysfunction Due to Ischemia and Reperfusion Injury
- ClinicalTrials.gov ID
- NCT00987974
- Acronym / sponsor ID
- FMD01
- Keywords
- ischemia reperfusion injury, endothelial dysfunction, statins, rosuvastatin, atorvastatin, placebo, ecto-5'-nucleotidase, flow mediated dilation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Feb 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 1 Oct 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:
Apart from their cholesterol lowering effects, statins have cholesterol-independent pleiotropic actions, such as upregulation of 5'-ectonucleotidase and up-regulation of NO-synthase that may increase tolerance against ischemia-reperfusion injury (IR-injury). Several animal studies have shown reduction of IR-injury as a result of statin treatment in both the heart and the kidney. Recently the investigators have shown, using Annexin A5 targeting after voluntary ischemic exercise to assess IR-injury, a protective effect of a 7 day oral rosuvastatin treatment. A three day treatment with atorvastatin however failed to reduce annexin targeting.
Assessment of the flow mediated dilation of the brachial artery as measure of endothelial (dys)function, is a validated model to research effects of possible protective strategies and perform mechanistic experiments on IR-injury in humans in vivo.
The investigators hypothesize that pretreatment with statins can increase endothelial tolerance against ischemia and reperfusion injury.
Objective:
To study the protective effect of pretreatment (both 3 day and 7 day) with rosuvastatin and atorvastatin on flow mediated dilation after 15 minutes ischemia and 15 minutes reperfusion.
Study design: placebo-controlled randomised double-blind trial
Study population: Healthy volunteers, age 18-50
Intervention: Treatment with either rosuvastatin 20 mg, atorvastatin 80mg or placebo during either 3 or 7 days
Main study parameters: Difference in flow mediated dilation before and after 15 minutes ischemia.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Treatment with rosuvastatin or atorvastatin is not expected to harm the volunteers. Most reported side effects of rosuvastatin and atorvastatin are gastro-intestinal complains and myalgia. The volunteers will not benefit directly from participating in this study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| rosuvastatin 3days | Experimental | Drug: rosuvastatin8 Subjects will use rosuvastatin 20 mg/day for 3 days |
| atorvastatin 3 days | Active comparator | Drug: atorvastatin 3 days8 Subjects will use atorvastatin 80 mg/day for 3 days.pj |
| placebo 3days | Placebo comparator | Drug: placebo8 Subjects will use placebo for 3 days. |
| rosuvastatin 7 days | Experimental | Drug: rosuvastatin 7 days8 Subjects will use rosuvastatin 20 mg/day for 7 days. |
| atorvastatin 7 days | Active comparator | Drug: atorvastatin 7 days8 Subjects will use atorvastatin 80 mg/day for 7 days. |
| placebo 7 days | Placebo comparator | Drug: placebo 7 days8 Subjects will use placebo for 7 days. |
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 (15 listed)
- Smoking
- 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)
- Hyperlipidaemia (fasting total cholesterol >5.5 mmol/L or random cholesterol >6.5 mmol/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 |
|---|---|---|
| rosuvastatinAlso: crestorrosuvastatin 20 mg/day for 3 days. | Drug | rosuvastatin 3days |
| atorvastatin 3 daysAlso: lipitoratorvastatin 80 mg/day for 3 days. | Drug | atorvastatin 3 days |
| placeboplacebo for 3 days. | Drug | placebo 3days |
| rosuvastatin 7 daysAlso: crestorrosuvastatin 20 mg/day for 7 days | Drug | rosuvastatin 7 days |
| atorvastatin 7 daysAlso: lipitoratorvastatin 80 mg/day for 7 days. | Drug | atorvastatin 7 days |
| placebo 7 daysplacebo 7 days | Drug | placebo 7 days |
Primary outcome
Difference in flow mediated dilation before and after 15 minutes ischemia
Time frame: 30 minutes
1 secondary outcome
Ecto-5'-nucleotidase activity and lipid profile after statin therapy
Time frame: 3-7 days
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 28 Apr 2010.
- Background: PubMed 19359665Meijer P, Oyen WJ, Dekker D, van den Broek PH, Wouters CW, Boerman OC, Scheffer GJ, Smits P, Rongen GA. Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection. Arterioscler Thromb Vasc Biol. 2009 Jun;29(6):963-8. doi: 10.1161/ATVBAHA.108.179622. Epub 2009 Apr 9.
- Background: PubMed 11273988Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.
- Derived from this study: PubMed 21885990Wouters CW, Wever KE, Bronckers I, Hopman MT, Smits P, Thijssen DH, Rongen GA. Short-term statin treatment does not prevent ischemia and reperfusion-induced endothelial dysfunction in humans. J Cardiovasc Pharmacol. 2012 Jan;59(1):22-8. doi: 10.1097/FJC.0b013e318232b1a4.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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, atorvastatin 3 days and rosuvastatin 7 days in people with Ischemia Reperfusion Injury and Endothelial Dysfunction, 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 15 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 28 Apr 2010. 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. Some participants in this study may receive a placebo. 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?
Difference in flow mediated dilation before and after 15 minutes ischemia (time frame: 30 minutes). 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 NCT00987974, which also lists 3 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 28 Apr 2010.