Effect of Simvastatin and Ezetimibe on Lipid and Inflammation
This study has been completed.
Sponsor:
Federal University of São Paulo
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
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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:
|
|
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:
|
|
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:
|
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
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:
|
Hypercholesterolemia Inflammation Glucose Intolerance Prediabetic State Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Pathologic Processes Hyperglycemia Glucose Metabolism Disorders Diabetes Mellitus |
Endocrine System Diseases Hypolipidemic Agents Simvastatin Ezetimibe Hydroxymethylglutaryl-CoA Reductase Inhibitors Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses Anticholesteremic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 17, 2013