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

August 12, 2013 updated by: Gian Paolo Fadini, University of Padova

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Padova, Italy, 35100
        • University Hospital Diabetes Outpatient Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Continue statin regimen
Patients randomized to this arm will continue their usual statin regimen and dose, without any intervention.
Experimental: Statin withdrawal
Patients randomized to this arm will stop statin treatment for 5 days.
Other: Statin withdrawal
Patients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in M1/M2 polarization
Time Frame: 5 days
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
Change in hsCRP
Time Frame: 5 days
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Padova

Investigators

  • Study Chair: Gian Paolo Fadini, M.D., University of Padova

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

May 15, 2012

First Submitted That Met QC Criteria

May 16, 2012

First Posted (Estimate)

May 17, 2012

Study Record Updates

Last Update Posted (Estimate)

August 13, 2013

Last Update Submitted That Met QC Criteria

August 12, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2616P

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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