Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients

Type 2 Diabetes Mellitus Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01600690
• Other study ID #: 2616P
• Status: Completed
• Phase: Phase 4
• First received: May 15, 2012
• Last updated: August 12, 2013
• Start date: May 2012
• Est. completion date: August 2013

Study information

• Verified date: August 2013
• Source: University of Padova
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical 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 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atherosclerosis
• Diabetes Mellitus, Type 2
• Dyslipidemia
• Dyslipidemias
• Type 2 Diabetes Mellitus

Intervention

Other:
• Statin withdrawal
Patients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged.

Locations

Country	Name	City	State
Italy	University Hospital Diabetes Outpatient Clinic	Padova

Sponsors (1)

Lead Sponsor	Collaborator
University of Padova

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	5 days	No
Secondary	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	5 days	No
Secondary	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	5 days	No