Type 2 Diabetes MellitusPhase 4SStatin-EPCNCT01600690
Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients
A Phase 4 study testing Statin withdrawal in people with Type 2 Diabetes Mellitus and Atherosclerosis, run by University of Padova at 1 site in Italy.
Trial summary
Statins are commonly prescribed to lower cardiovascular risk in primary and secondary prevention. Despite their well known efficacy, statin withdrawal is a common event. Even a short term statin withdrawal can have dramatic consequences on atherosclerotic plaque stability, owing to a rebound in cholesterol levels and… Read more about this study
- Who is it for?
- Ages 35 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus, Atherosclerosis, Dyslipidemia
- What is being tested?
- Statin withdrawal
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteItaly
- Study dates
- May 2012to Aug 2013
- 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 35 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes mellitus
- Age 35-80
- Males and Females
- eGFR>30 ml/min/1.73 mq
- On statin therapy from at least 6 months
- Minimal statin dosage: Simvastatin 10 mg; Pravastatin 40 mg; Fluvastatin 80 mg; Rosuvastatin 5 mg; Atorvastatin 10 mg.
Who cannot join
- Type 1 diabetes mellitus
- Age <35 or >80
- Chronic renal failure (eGFR<30 ml/min/1.73 mq)
- Recent (within 1 month) acute diseases or trauma or surgery
- Chronic inflammatory diseases (e.g. rheumatoid arthritis)
- Active cancer
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- LDL cholesterol > 160 mg/dL
- Carotid atherosclerosis (>30% stenosis), coronary artery disease, peripheral arterial disease (Leriche stages II-IV)
- On ezetimibe, fibrates, or niacin
- Therapy with EP hormones
- Pregnancy or lactation
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients. A Controlled Randomized Study
Statins are commonly prescribed to lower cardiovascular risk in primary and secondary prevention. Despite their well known efficacy, statin withdrawal is a common event. Even a short term statin withdrawal can have dramatic consequences on atherosclerotic plaque stability, owing to a rebound in cholesterol levels and inflammation.
The effects of a short term statin withdrawal on endothelial progenitor cells (EPC) and monocyte/macrophage polarization is unknown.
Read more
In this study, the investigators will explore the effects of a 5-day statin withdrawal on EPC and monocyte/macrophage polarization, together with other inflammatory biomarkers in type 2 diabetic patients. The investigators hypothesize that statin withdrawal determines a reduction in EPC levels and an inflammatory cell polarization.
Patients will be randomized to continue their habitual statin regimen or to withdraw statin. At baseline and 5 days later, blood samples will be collected for experimental measures.
Read the detailed description
Statins are commonly prescribed to lower cardiovascular risk in primary and secondary prevention. Despite their well known efficacy with relatively low NNTs, statin withdrawal is a common event for several reasons. Patients often stop statin therapies for long or short periods of time. Even a short term statin withdrawal can have dramatic consequences on atherosclerotic plaque stability, owing to a rebound in cholesterol levels and inflammation. Previous studies have demonstrated worsening of inflammation and endothelial function after a short-term statin withdrawal. This may be even more dramatic in patients who are at increased risk of cardiovascular disease, such as diabetic patients.
Endothelial integrity is accomplished through the contribution of circulating endothelial progenitor cells (EPC) which repair the damaged endothelial layer and contribute to cardiovascular health in general. EPC are stimulated by statins, but there is no data on the effect of statin withdrawal on EPCs.
One important aspect of inflammation is the pro- versus anti-inflammatory polarization of circulating monocyte/macrophage (MM) cells. Schematically, MM can exist in 2 different states of activation: the classically activated pro-inflammatory cells (M1) and the alternatively activated anti-inflammatory cells (M2). The balance between these 2 (M1/M2 ratio) reflects the state of MM polarization. The effects of statin withdrawal on MM polarization is unknown.
In this study, we will explore the effects of a 5-day statin withdrawal on EPC and monocyte/macrophage polarization, together with other inflammatory biomarkers (namely high sensitive C-reactive protein) in type 2 diabetic patients. We hypothesise that statin withdrawal determines a reduction in EPC levels and an inflammatory cell polarization.
Patients will be randomized to continue their habitual statin regimen or to withdraw statin. At baseline and 5 days later, blood samples will be collected for experimental measures (EPC, M1, M2 and hsCRP).
- Conditions
- Type 2 Diabetes Mellitus, Atherosclerosis, Dyslipidemia
- Being tested
- Statin withdrawal
- Keywords
- Stem cells, Regeneration, Inflammation
- Medical subject headings
- Diabetes Mellitus, Type 2, Atherosclerosis, Dyslipidemias, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Statin withdrawalOther
Patients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged.
| Study group | Role | What they receive |
|---|---|---|
| Continue statin regimen | No intervention | Patients randomized to this arm will continue their usual statin regimen and dose, without any intervention. |
| Statin withdrawal | Experimental | Patients randomized to this arm will stop statin treatment for 5 days. Receives: Other: Statin withdrawal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in EPC levels
Change in EPC levels at day 5 versus baseline will be compared between patients who continued taking statins and patients who withdrawed
Measured: 5 days
Secondary outcomes (2)
Change in M1/M2 polarization
Change in monocyte macrophage pro- (M1) versus anti- (M2) inflammatory polarization at day 5 versus baseline will be compared between patients who continued taking statins and patients who withdrawed
Measured: 5 days
Change in hsCRP
Change in high sensitive C-reactive protein levels at day 5 versus baseline will be compared between patients who continued taking statins and patients who withdrawed
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2012 (estimated)
- Study startMay 2012
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- 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
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gian Paolo Fadini, University of Padova
- Investigators
- Gian Paolo Fadini, M.D., Study chair, University of Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01600690
- Sponsor's protocol ID
- 2616P
- Acronym
- SStatin-EPC
- Status last verified
- Aug 2013
- First submitted
- 15 May 2012
- Last updated
- 13 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients. A Controlled Randomized Study
- ClinicalTrials.gov ID
- NCT01600690
- Acronym / sponsor ID
- SStatin-EPC / 2616P
- Conditions
- Type 2 Diabetes Mellitus, Atherosclerosis, Dyslipidemia
- Keywords
- Stem cells, Regeneration, Inflammation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 17 May 2012 (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.
Statins are commonly prescribed to lower cardiovascular risk in primary and secondary prevention. Despite their well known efficacy, statin withdrawal is a common event. Even a short term statin withdrawal can have dramatic consequences on atherosclerotic plaque stability, owing to a rebound in cholesterol levels and inflammation.
The effects of a short term statin withdrawal on endothelial progenitor cells (EPC) and monocyte/macrophage polarization is unknown.
In this study, the investigators will explore the effects of a 5-day statin withdrawal on EPC and monocyte/macrophage polarization, together with other inflammatory biomarkers in type 2 diabetic patients. The investigators hypothesize that statin withdrawal determines a reduction in EPC levels and an inflammatory cell polarization.
Patients will be randomized to continue their habitual statin regimen or to withdraw statin. At baseline and 5 days later, blood samples will be collected for experimental measures.
Detailed description
Statins are commonly prescribed to lower cardiovascular risk in primary and secondary prevention. Despite their well known efficacy with relatively low NNTs, statin withdrawal is a common event for several reasons. Patients often stop statin therapies for long or short periods of time. Even a short term statin withdrawal can have dramatic consequences on atherosclerotic plaque stability, owing to a rebound in cholesterol levels and inflammation. Previous studies have demonstrated worsening of inflammation and endothelial function after a short-term statin withdrawal. This may be even more dramatic in patients who are at increased risk of cardiovascular disease, such as diabetic patients.
Endothelial integrity is accomplished through the contribution of circulating endothelial progenitor cells (EPC) which repair the damaged endothelial layer and contribute to cardiovascular health in general. EPC are stimulated by statins, but there is no data on the effect of statin withdrawal on EPCs.
One important aspect of inflammation is the pro- versus anti-inflammatory polarization of circulating monocyte/macrophage (MM) cells. Schematically, MM can exist in 2 different states of activation: the classically activated pro-inflammatory cells (M1) and the alternatively activated anti-inflammatory cells (M2). The balance between these 2 (M1/M2 ratio) reflects the state of MM polarization. The effects of statin withdrawal on MM polarization is unknown.
In this study, we will explore the effects of a 5-day statin withdrawal on EPC and monocyte/macrophage polarization, together with other inflammatory biomarkers (namely high sensitive C-reactive protein) in type 2 diabetic patients. We hypothesise that statin withdrawal determines a reduction in EPC levels and an inflammatory cell polarization.
Patients will be randomized to continue their habitual statin regimen or to withdraw statin. At baseline and 5 days later, blood samples will be collected for experimental measures (EPC, M1, M2 and hsCRP).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continue statin regimen | No intervention | –Patients randomized to this arm will continue their usual statin regimen and dose, without any intervention. |
| Statin withdrawal | Experimental | Other: Statin withdrawalPatients randomized to this arm will stop statin treatment for 5 days. |
Who may qualify
- Ages
- 35 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Type 2 diabetes mellitus
- Age 35-80
- Males and Females
- eGFR>30 ml/min/1.73 mq
- On statin therapy from at least 6 months
Key exclusion criteria (12 listed)
- Type 1 diabetes mellitus
- Age <35 or >80
- Chronic renal failure (eGFR<30 ml/min/1.73 mq)
- Recent (within 1 month) acute diseases or trauma or surgery
- Chronic inflammatory diseases (e.g. rheumatoid arthritis)
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 |
|---|---|---|
| Statin withdrawalPatients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged. | Other | Statin withdrawal |
Primary outcome
Change in EPC levels
Time frame: 5 days
Change in EPC levels at day 5 versus baseline will be compared between patients who continued taking statins and patients who withdrawed
2 secondary outcomes
Change in M1/M2 polarization
Time frame: 5 days
Change in hsCRP
Time frame: 5 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 13 Aug 2013.
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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.
Gian Paolo Fadini, M.D. study chair
University of Padova
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 Statin withdrawal in people with Type 2 Diabetes Mellitus and Atherosclerosis, run by University of Padova at 1 site in Italy.
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 6 inclusion and 12 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 13 Aug 2013. 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 Italy. 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?
Change in EPC levels (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2013.