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

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ClinicalTrials.gov Identifier: NCT01600690
Recruitment Status : Completed
First Posted : May 17, 2012
Last Update Posted : August 13, 2013
Sponsor:
Information provided by (Responsible Party):
Gian Paolo Fadini, University of Padova

Tracking Information
First Submitted Date  ICMJE May 15, 2012
First Posted Date  ICMJE May 17, 2012
Last Update Posted Date August 13, 2013
Study Start Date  ICMJE May 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01600690 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2012)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of 5-day Statin Withdrawal on Endothelial Progenitor Cells and Inflammatory Markers in Type 2 Diabetic Patients
Official Title  ICMJE 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
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Type 2 Diabetes Mellitus
  • Atherosclerosis
  • Dyslipidemia
Intervention  ICMJE Other: Statin withdrawal
Patients are instructed to stop taking statin pills for the duration of the study. The rest of therapy will remain unchanged.
Study Arms  ICMJE
  • 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.
    Intervention: Other: Statin withdrawal
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 12, 2013)
34
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2012)
42
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01600690
Other Study ID Numbers  ICMJE 2616P
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gian Paolo Fadini, University of Padova
Study Sponsor  ICMJE University of Padova
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Gian Paolo Fadini, M.D. University of Padova
PRS Account University of Padova
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP