Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients (SStatin-EPC)
Primary Purpose
Type 2 Diabetes Mellitus, Atherosclerosis, Dyslipidemia
Status
Completed
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Statin withdrawal
Sponsored by
About this trial
This is an interventional prevention trial for Type 2 Diabetes Mellitus focused on measuring Stem cells, Regeneration, Inflammation
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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
Sites / Locations
- University Hospital Diabetes Outpatient Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Continue statin regimen
Statin withdrawal
Arm Description
Patients randomized to this arm will continue their usual statin regimen and dose, without any intervention.
Patients randomized to this arm will stop statin treatment for 5 days.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01600690
Brief Title
Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients
Acronym
SStatin-EPC
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Padova
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus, Atherosclerosis, Dyslipidemia
Keywords
Stem cells, Regeneration, Inflammation
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Continue statin regimen
Arm Type
No Intervention
Arm Description
Patients randomized to this arm will continue their usual statin regimen and dose, without any intervention.
Arm Title
Statin withdrawal
Arm Type
Experimental
Arm Description
Patients randomized to this arm will stop statin treatment for 5 days.
Intervention Type
Other
Intervention Name(s)
Statin withdrawal
Intervention Description
Patients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged.
Primary Outcome Measure Information:
Title
Change in EPC levels
Description
Change in EPC levels at day 5 versus baseline will be compared between patients who continued taking statins and patients who withdrawed
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Change in M1/M2 polarization
Description
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
Time Frame
5 days
Title
Change in hsCRP
Description
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
Time Frame
5 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gian Paolo Fadini, M.D.
Organizational Affiliation
University of Padova
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital Diabetes Outpatient Clinic
City
Padova
ZIP/Postal Code
35100
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients
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