Effect of Simvastatin and Ezetimibe on Lipid and Inflammation

This study has been completed.
Sponsor:
Information provided by:
Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT01103648
First received: April 12, 2010
Last updated: April 14, 2010
Last verified: November 2007
  Purpose

Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol and plant sterols. Synergism of ezetimibe-statin therapy on LDL-cholesterol has been demonstrated, but data concerning the pleiotropic effects of this combination are controversial. We tested the hypothesis that the combination of simvastatin and ezetimibe would induce improvement in inflammatory status, as reflected by leukocyte count and CRP, IL-6 and TNF-a levels. This open-label trial evaluated whether this combination results in a synergistic effect the pro-inflammatory status of pre-diabetic subjects. Fifty pre-diabetic subjects were randomly assigned to one of 2 groups, one receiving ezetimibe (10 mg/d), the other, simvastatin (20 mg/d) for 12 weeks, followed by an additional 12-week period of combined therapy.


Condition Intervention
Prediabetes
Hypercholesterolemia
Inflammation
Cardiovascular Risk
Drug: Simvastatin
Drug: Ezetimibe
Drug: Combination Simvastatin plus Ezetimibe

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Synergistic Effect of Simvastatin and Ezetimibe on Lipid and Pro-inflammatory Profiles in Pre-diabetic Subjects

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • C reactive protein [ Time Frame: Serum C reactive protein was detected at baseline, before starting monotherapy with simvastatin or ezetimibe, and after 12 weeks of each monotherapy ] [ Designated as safety issue: No ]
    CRP is one of the most important inflammatory marker and its determination has been considered a non-traditional risk factor for several chronic diseases including diabetes and cardiovascular diseases.

  • C reactive protein [ Time Frame: C reactive protein (CRP) concentration was determined after 12 weeks of monotherapy (simvastatin or ezetimibe) and was compared with the concentration after more 12 weeks of combined therapy ] [ Designated as safety issue: No ]
    CRP is one of the most important inflammatory marker and its determination has been considered a non-traditional risk factor for several chronic diseases including diabetes and cardiovascular diseases.

  • C reactive protein [ Time Frame: Serum C reactive protein (CRP) concentration detected at baseline was compared with that obtained after of combined therapy of simvastatin plus ezetimibe (week 24) ] [ Designated as safety issue: No ]
    CRP is one of the most important inflammatory marker and its determination has been considered a non-traditional risk factor for several chronic diseases including diabetes and cardiovascular diseases.


Secondary Outcome Measures:
  • Interleukin-6 [ Time Frame: Circulating interleukin-6 concentration was determined at baseline (before monotherapy with simvastatin or ezetimibe) and after a 12-week period of each monotherapy ] [ Designated as safety issue: No ]
    Interleukin-6 (IL-6) is a cytokine also produced by the adiposo tissue; its measurement in blood has been used as inflammatory marker for research purposes.

  • Tumor necrosis factor alpha [ Time Frame: Tumor necrosis factor alfa concentration was determined at baseline (before monotherapy with simvastatin or ezetimibe) and after a 12-week period of each monotherapy ] [ Designated as safety issue: No ]
    Tumor necrosis factor alfa (TNF-alpha) is secreted by adipose tissue and released to blood. Circulating levels of TNF-alpha may be indicative of a proinflammatory status, which is a initiating mechanism of metabolic and cardiovascular abnormalities.

  • Interleukin-6 [ Time Frame: Interleukin-6 concentration was determined after 12 weeks of monotherapy with simvastatin or ezetimibe and compared with the concentrations after more 12 weeks of combined therapy ] [ Designated as safety issue: No ]
    Interleukin-6 (IL-6) is a cytokine also produced by the adiposo tissue; its measurement in blood has been used as inflammatory marker for research purposes.

  • Tumor Necrosis Factor Alpha [ Time Frame: Serum tumor necrosis factor alpha concentration was determined after 12 weeks of monotherapy with simvastatin or ezetimibe and compared with the concentrations after more 12 weeks of combined therapy ] [ Designated as safety issue: No ]
    Tumor necrosis factor alfa (TNF-alpha) is secreted by adipose tissue and released to blood. Circulating levels of TNF-alpha may be indicative of a proinflammatory status, which is a initiating mechanism of metabolic and cardiovascular abnormalities.

  • Interleukin-6 [ Time Frame: Interleukin-6 concentration detected at baseline was compared with that obtained after of combined therapy of simvastatin plus ezetimibe (week 24) ] [ Designated as safety issue: No ]
    nterleukin-6 (IL-6) is a cytokine also produced by the adiposo tissue; its measurement in blood has been used as inflammatory marker for research purposes.

  • Tumor necrosis factor alpha [ Time Frame: Tumor necrosis factor alpha concentration detected at baseline was compared with that obtained after of combined therapy of simvastatin plus ezetimibe (week 24) ] [ Designated as safety issue: No ]
    Tumor necrosis factor alfa (TNF-alpha) is secreted by adipose tissue and released to blood. Circulating levels of TNF-alpha may be indicative of a proinflammatory status, which is a initiating mechanism of metabolic and cardiovascular abnormalities.


Enrollment: 50
Study Start Date: June 2005
Study Completion Date: November 2007
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Simvastatin arm
A subset of individuals started the study period taking monotherapy with simvastatin. After a 12-week period, ezetimibe was combined to the initial monotherapy for more 12 weeks (combination period = experimental).
Drug: Simvastatin
Tablets of simvastatin 20 mg administered once a day for 12 weeks
Other Names:
  • Simvastatin
  • Statin
Active Comparator: Ezetimibe arm
A subset of individuals started the study period taking monotherapy with ezetimibe. After a 12-week period, simvastin was combined to the initial monotherapy for more 12 weeks (combination period = experimental).
Drug: Ezetimibe
Tablets of ezetimibe 10 mg administered once a day for 12 weeks
Other Names:
  • Ezetimibe
  • Lipid-lowering drug
Experimental: Simvastatin-Ezetimibe arm
To each subset of individuals which started the study period taking monotherapy with simvastatin or ezetimibe (active comparators), the other drug (ezetimibe or simvastatin, respectively) was combined for more 12 weeks (combination period = experimental arm).
Drug: Combination Simvastatin plus Ezetimibe

Simvastatin 20 mg, once a day, was administered for an additional 12-week period for the subset of individuals who took the initial monotherapy with ezetimibe 10 mg (12 week duration).

Ezetimibe 10 mg, once a day, was administered for an additional 12-week period for the subset of individuals who took the initial monotherapy with simvastatin 20 mg (12 week duration).

This Combination represents the experimental period of the present study.

Other Names:
  • Simvastatin
  • Statin
  • Ezetimibe
  • Lipid-lowering drugs

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Both sexes, aged from 18 to 75 years, with a body mass index ranging from 25 to 40 kg/m2 and pre-diabetes (impaired glucose tolerance or impaired fasting glucose).

Exclusion Criteria:

  • Blood triglyceride concentration >350 mg/dl and LDL cholesterol >200 mg/dl, unstable blood pressure, clinical evidences of cardiovascular, hepatic or renal diseases, use of anti-inflammatory agents or others interfering with lipid or glucose metabolism.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01103648

Locations
Brazil
Hospital do Rim e Hipertensao da UNIFESP
Sao Paulo, Brazil, 04038-002
Sponsors and Collaborators
Federal University of São Paulo
Investigators
Principal Investigator: Sandra RG Ferreira, PhD Federal University of Sao Paulo
  More Information

Additional Information:
No publications provided

Responsible Party: Sandra Roberta Gouvea Ferreira, Federal University of Sao Paulo
ClinicalTrials.gov Identifier: NCT01103648     History of Changes
Other Study ID Numbers: FUSaoPaulo
Study First Received: April 12, 2010
Last Updated: April 14, 2010
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Federal University of São Paulo:
Prediabetes
Statin
Ezetimibe
Pleiotropic effects
Cardiometabolic risk

Additional relevant MeSH terms:
Inflammation
Hypercholesterolemia
Glucose Intolerance
Prediabetic State
Pathologic Processes
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hyperglycemia
Glucose Metabolism Disorders
Diabetes Mellitus
Endocrine System Diseases
Simvastatin
Ezetimibe
Hypolipidemic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014