Diabetes MellitusPhase 2STOPCAPNCT00166036
Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells
A Phase 2 study testing Atorvastatin and Pravastatin in people with Diabetes Mellitus and Metabolic Syndrome X, run by Emory University at 1 site in United States.
Trial summary
Thirty-six subjects with hyperlipidemia and metabolic syndrome and/or diabetes were randomized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily. Oxidative stress (dROMs assay that measures lipid hydroperoxides, plasma thiobarbituric acid reactive substances [TBARS], and aminothiol… Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Diabetes Mellitus, Metabolic Syndrome X, Hypercholesterolemia
- What is being tested?
- Atorvastatin and Pravastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to Apr 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females without child bearing potential aged 21-80 years
- Fasting low-density lipoprotein (LDL) level > 120mg/dL.
- Either known to be diabetic or have at least 3 components of metabolic syndrome that are defined below:
- Hypertension defined as blood pressure (BP) > 140 systolic or > 90 mmHg diastolic, or stable medical therapy for documented hypertension;
- Fasting glucose > 110 mg/dL;
- Waist > 40 inches in males, and > 35 inches in females;
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- Triglycerides > 150mg/dL; or
- High-density lipoprotein (HDL) cholesterol < 40 mg/dL in males and < 50 mg/dL in females.
- Able to provide written informed consent
- Non-smoker
Who cannot join
- On any oral antioxidants or lipid lowering medications in the previous 8 weeks
- Age < 21 or > 80 years
- Premenopausal females with potential for pregnancy
- LDL cholesterol level < 120 mg/dl
- Initiation or change in dose of any concomitant medical therapy within 2 months before the study
- Uncontrolled hypertension with BP > 180 mmHg systolic and > 120 mmHg diastolic
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- Current smoker
- Previous intolerance or allergy to statins
- Acute infection in previous 4 weeks
- History of substance abuse
- Uninterpretable Brachial Artery Reactivity Study
- Current neoplasm
- Chronic renal failure (creatinine > 2.5 mg/dL) or liver failure (liver enzymes > 2X normal)
- Acute coronary syndrome, heart failure, cerebrovascular accident (CVA), or coronary intervention within 3 months
- Known aortic stenosis, hypertrophic cardiomyopathy, or symptomatic heart failure.
- Inability to give informed consent
- Inability to return to Emory for follow-up
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells: Comparison of Atorvastatin With Pravastatin
Thirty-six subjects with hyperlipidemia and metabolic syndrome and/or diabetes were randomized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily. Oxidative stress (dROMs assay that measures lipid hydroperoxides, plasma thiobarbituric acid reactive substances [TBARS], and aminothiol levels) and brachial artery flow-mediated dilation (FMD) were measured at baseline and after 12 weeks of statin therapy.
Read the detailed description
Individuals with a high cholesterol level, diabetes or metabolic syndrome (collection of abnormalities such as high blood pressure, high triglyceride levels [fat], obesity, high blood glucose level) have an increased risk of developing a hardening of the arteries and heart disease.
A group of medications called statins, commonly used worldwide to lower cholesterol levels, are known to reduce the risk of heart disease through their effects on reducing cholesterol levels. These medications also have effects beyond the lowering of cholesterol that may help mediate their beneficial effects on the heart and blood vessels.
These include a reduced production of molecules that harm the arteries such as reactive oxygen species (ROS) and increasing the number of stem cells that help repair vessels, called endothelial progenitor cells (EPCs).
Recent studies have shown that different statins might have different effects on protecting people from developing heart disease. These differences may be due to differences in these non-cholesterol lowering processes, and are the subject of this study.
Standard of Care:
The two statins that will be used in this study, pravastatin (Pravachol ®) and atorvastatin (Lipitor®), are approved for use in people with a high cholesterol level or heart disease. These medications are generally very well tolerated with minimal side effects. They are not approved for use in patients to increase the level of EPCs or to reduce the production of ROS, and therefore are considered experimental for this indication. Currently there are no drugs that are specifically approved for these indications.
How the Problem Will be Studied:
These statins will be given to patients who have high cholesterol and either diabetes or the metabolic syndrome once a day for 12 weeks. We, the investigators at Emory, will measure the level of EPCs and ROS before and during the administration of the statin. We will also investigate how well the blood vessels dilate in response to these medications by performing an imaging study of the forearm artery using ultrasound.
The study is blinded and there is an equal chance of receiving either atorvastatin 10mg or pravastatin 80mg which are likely to lower cholesterol level by a similar amount.
How Research Will Advance Scientific Knowledge:
The goal of this study is to determine if atorvastatin will increase the number of circulating EPCs and reduce the production of ROS more than pravastatin. This may help explain the differences between these drugs that have been observed in some recently published trials.
- Being tested
- Atorvastatin, Pravastatin
- Medical subject headings
- Diabetes Mellitus, Metabolic Syndrome, Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
12 Weeks of Oral Atorvastatin 10 mg therapy.
PravastatinDrug
12 Weeks of Oral Pravastatin 80 mg therapy.
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin 10MG | Experimental | Not described Receives: Drug: Atorvastatin |
| Pravastatin 80mg | Experimental | Not described Receives: Drug: Pravastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Plasma Thiobarbituric Acid Reactive Substance (TBARS) Levels
Oxidative stress was assessed with plasma thiobarbituric acid reactive substance (TBARS) levels (an index of lipid peroxidation).Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage.We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.
Measured: Baseline &12 Weeks
Secondary outcomes (1)
Change in Flow-mediated Dilatation (FMD)
Flow-mediated dilatation (FMD) of the brachial artery was used to asses Endothelial Function. The endothelium, by releasing nitric oxide (NO), promotes vasodilation and inhibits inflammation, thrombosis, and vascular smooth muscle cell proliferation.We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.
Measured: Baseline & 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startSep 2004
- Primary completionMar 2008
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arshed A. Quyyumi, Emory University
- Investigators
- Arshed A Quyyumi, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00166036
- Sponsor's protocol ID
- 1038-2004
- Acronym
- STOPCAP
- Status last verified
- Aug 2014
- First submitted
- 12 Sep 2005
- Last updated
- 8 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Murrow JR, Sher S, Ali S, Uphoff I, Patel R, Porkert M, Le NA, Jones D, Quyyumi AA. The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. J Clin Lipidol. 2012 Jan-Feb;6(1):42-9. doi: 10.1016/j.jacl.2011.08.006. Epub 2011 Sep 13.
PubMed 22264573
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells: Comparison of Atorvastatin With Pravastatin
- ClinicalTrials.gov ID
- NCT00166036
- Acronym / sponsor ID
- STOPCAP / 1038-2004
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Sep 2004
- Primary completion
- Mar 2008 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 14 Sep 2005 (estimated)
- Results
- Posted 8 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Thirty-six subjects with hyperlipidemia and metabolic syndrome and/or diabetes were randomized in a double-blind manner to either pravastatin 80 mg or atorvastatin 10 mg daily. Oxidative stress (dROMs assay that measures lipid hydroperoxides, plasma thiobarbituric acid reactive substances [TBARS], and aminothiol levels) and brachial artery flow-mediated dilation (FMD) were measured at baseline and after 12 weeks of statin therapy.
Detailed description
Individuals with a high cholesterol level, diabetes or metabolic syndrome (collection of abnormalities such as high blood pressure, high triglyceride levels [fat], obesity, high blood glucose level) have an increased risk of developing a hardening of the arteries and heart disease.
A group of medications called statins, commonly used worldwide to lower cholesterol levels, are known to reduce the risk of heart disease through their effects on reducing cholesterol levels. These medications also have effects beyond the lowering of cholesterol that may help mediate their beneficial effects on the heart and blood vessels.
These include a reduced production of molecules that harm the arteries such as reactive oxygen species (ROS) and increasing the number of stem cells that help repair vessels, called endothelial progenitor cells (EPCs).
Recent studies have shown that different statins might have different effects on protecting people from developing heart disease. These differences may be due to differences in these non-cholesterol lowering processes, and are the subject of this study.
Standard of Care:
The two statins that will be used in this study, pravastatin (Pravachol ®) and atorvastatin (Lipitor®), are approved for use in people with a high cholesterol level or heart disease. These medications are generally very well tolerated with minimal side effects. They are not approved for use in patients to increase the level of EPCs or to reduce the production of ROS, and therefore are considered experimental for this indication. Currently there are no drugs that are specifically approved for these indications.
How the Problem Will be Studied:
These statins will be given to patients who have high cholesterol and either diabetes or the metabolic syndrome once a day for 12 weeks. We, the investigators at Emory, will measure the level of EPCs and ROS before and during the administration of the statin. We will also investigate how well the blood vessels dilate in response to these medications by performing an imaging study of the forearm artery using ultrasound.
The study is blinded and there is an equal chance of receiving either atorvastatin 10mg or pravastatin 80mg which are likely to lower cholesterol level by a similar amount.
How Research Will Advance Scientific Knowledge:
The goal of this study is to determine if atorvastatin will increase the number of circulating EPCs and reduce the production of ROS more than pravastatin. This may help explain the differences between these drugs that have been observed in some recently published trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin 10MG | Experimental | Drug: Atorvastatin |
| Pravastatin 80mg | Experimental | Drug: Pravastatin |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Males or females without child bearing potential aged 21-80 years
- Fasting low-density lipoprotein (LDL) level > 120mg/dL.
- Either known to be diabetic or have at least 3 components of metabolic syndrome that are defined below:
- Able to provide written informed consent
- Non-smoker
Key exclusion criteria (17 listed)
- On any oral antioxidants or lipid lowering medications in the previous 8 weeks
- Age < 21 or > 80 years
- Premenopausal females with potential for pregnancy
- LDL cholesterol level < 120 mg/dl
- Initiation or change in dose of any concomitant medical therapy within 2 months before the study
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 |
|---|---|---|
| Atorvastatin12 Weeks of Oral Atorvastatin 10 mg therapy. | Drug | Atorvastatin 10MG |
| Pravastatin12 Weeks of Oral Pravastatin 80 mg therapy. | Drug | Pravastatin 80mg |
Primary outcome
Change in Plasma Thiobarbituric Acid Reactive Substance (TBARS) Levels
Time frame: Baseline &12 Weeks
Oxidative stress was assessed with plasma thiobarbituric acid reactive substance (TBARS) levels (an index of lipid peroxidation).Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage.We hypothesized that equipotent doses of these two statins will have divergent effects on markers of oxidative stress and endothelial function.
1 secondary outcome
Change in Flow-mediated Dilatation (FMD)
Time frame: Baseline & 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22264573Murrow JR, Sher S, Ali S, Uphoff I, Patel R, Porkert M, Le NA, Jones D, Quyyumi AA. The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. J Clin Lipidol. 2012 Jan-Feb;6(1):42-9. doi: 10.1016/j.jacl.2011.08.006. Epub 2011 Sep 13.
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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.
Arshed A Quyyumi, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atorvastatin and Pravastatin in people with Diabetes Mellitus and Metabolic Syndrome X, run by Emory University at 1 site in United States.
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 10 inclusion and 17 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 8 Sep 2014. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Plasma Thiobarbituric Acid Reactive Substance (TBARS) Levels (time frame: Baseline &12 Weeks). 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 NCT00166036, 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 8 Sep 2014.