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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gian Paolo Fadini, University of Padova
ClinicalTrials.gov Identifier:
NCT01600690
First received: May 15, 2012
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Atherosclerosis
Dyslipidemia
Other: Statin withdrawal
Phase 4

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

Resource links provided by NLM:


Further study details as provided by University of Padova:

Primary Outcome Measures:
  • Change in EPC levels [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Enrollment: 34
Study Start Date: May 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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).

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01600690

Locations
Italy
University Hospital Diabetes Outpatient Clinic
Padova, Italy, 35100
Sponsors and Collaborators
University of Padova
Investigators
Study Chair: Gian Paolo Fadini, M.D. University of Padova
  More Information

No publications provided

Responsible Party: Gian Paolo Fadini, Assistant Professor, University of Padova
ClinicalTrials.gov Identifier: NCT01600690     History of Changes
Other Study ID Numbers: 2616P
Study First Received: May 15, 2012
Last Updated: August 12, 2013
Health Authority: Italy: Ministry of Health

Keywords provided by University of Padova:
Stem cells
Regeneration
Inflammation

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Diabetes Mellitus
Diabetes Mellitus, Type 2
Dyslipidemias
Arterial Occlusive Diseases
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014