Anti-inflammatory Effects of Simvastatin

Comparison of Effects of Simvastatin Versus Ezetimibe on Intracellular Lipid and Inflammation in Obese Subjects

The purpose of this research study is to determine which of the two ingredients of Vytorin (Simvastatin or Ezetimibe) is responsible for the anti-inflammatory effects of Vytorin

Study Overview

• Status: Terminated
• Conditions: Inflammation; Atherosclerosis; Hypercholesterolemia
• Intervention / Treatment: Drug: Simvastatin 40mg; Drug: Ezetimibe 10mg

Detailed Description

Cardiovascular disease is currently the leading cause of death in the developed countries. Atherosclerosis is the most important cause of cardiovascular disease. Statins are known to exert a powerful anti-atherogenic action which is reflected in a marked beneficial effect on the prevention of cardiovascular effects and cardiovascular mortality. They induce a reduction in the progression and an increase in the regression of atherosclerotic lesions. Statins exert powerful effect on lowering LDLc and are also anti-inflammatory due to their ability to lower CRP concentrations. But little is known about their anti-inflammatory effects at a cellular and molecular levels in humans, in vivo.

Vytorin, a preparation containing simvastatin and ezetimibe, has a powerful effect on lowering LDLc concentration through a combination of effects on the absorption of cholesterol from the gut and hepatic cholesterol biosynthesis. In our previous study we have shown that Vytorin exerts a potent anti-inflammatory effect in the obese in the fasting state and following acute inflammatory changes induced by the intake of cream. The IMPROVE-IT trial, which examined the benefits of adding ezetimibe to simvastatin, showed a small additional benefit of ezetimibe (a 6% reduction in cardiovascular events) compared to simvastatin alone. This is marginal when compared to the established cardiovascular benefits of statins.

We, therefore, explore further into the anti-inflammatory actions of the two components of Vytorin by comparing the effects of simvastatin versus ezetimibe on intracellular lipid and inflammation in obese patients to determine which of the two ingredients of Vytorin is responsible for the specific combination of these effects.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14221
      • Diabetes and Endocrinology Research Center of WNY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age: 18 to 75 years of age.
2. Obese (BMI ≥30 kg/m2)
3. LDL cholesterol of ≥100 mg/dl
4. Not taking any vitamins or antioxidants

Exclusion Criteria:

1. Currently using anti-hyperlipidemic therapies
2. Triglycerides >500 mg/dl.
3. Myocardial infarction, angioplasty/stent placement or coronary artery bypass surgery in the past 6 months.
4. Patient on chronic use of non-steroidal anti-inflammatory drugs or steroids
5. Hepatic disease
6. Renal impairment.
7. History of drug or alcohol abuse
8. Participation in any other concurrent clinical trial
9. Use of an investigational agent or therapeutic regimen within 30 days of study.
10. Smoker
11. Pregnancy
12. Premenopausal women who are not on birth control pills and have not had a hysterectomy or tubal ligation
13. Anemia with hemoglobin <12 g/dl

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Simvastatin; Obese subjects with elevated cholesterol	Drug: Simvastatin 40mg; Simvastatin administered daily for 6 weeks; Other Names: Simvastatin
Active Comparator: Ezetimibe; Obese subjects with elevated cholesterol	Drug: Ezetimibe 10mg; Ezetimibe administered daily for 6 weeks; Other Names: Zetia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mRNA Expression of CD68 in MNC	Percentage change in mRNA expression of CD68 in MNC following cream challenge at weeks 0 and 6 of treatment with simvastatin or ezetimibe. Percent change (using the formula: (x-y)/y*100) is calculated using data collected before (0hr) and after the cream challenge (peak effect) at weeks 0 and 6 of treatment with simvastatin or ezetimibe.	6 weeks
Change in mRNA Expression of PECAM on MNC	Percentage change in mRNA expression of PECAM on MNC following cream challenge before and after 6 weeks of treatment with simvastatin or ezetimibe. Percent change (using the formula: (x-y)/y*100) was calculated using data collected before (0hr) and after the cream challenge (peak effect) at weeks 0 and 6 of treatment with simvastatin or ezetimibe.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mRNA Expression of IL-1β in MNC	Percentage change in mRNA expression of IL-1β in MNC following cream challenge calculated from data collected before (at 0 week) and after (at 6 weeks) treatment with simvastatin or ezetimibe	6 weeks
Change in TNF-a mRNA Expression in MNC	Percentage change in mRNA expression of TNFα in MNC following cream challenge calculated using data collected before and after the cream challenge at weeks 0 and 6 of treatment with simvastatin or ezetimibe	6 weeks
Change in mRNA Expression of MMP-9 in MNC	Percentage change in mRNA expression of MMP-9 in MNC calculated from data collected following cream challenge before (0 week) and after (6 weeks) of treatment with simvastatin or ezetimibe	6 weeks

Collaborators and Investigators

• Sponsor: paresh Dandona
• Investigators: Principal Investigator: Paresh Dandona, MD, PhD, Distinguished Professor of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): August 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Inflammation; Hypercholesterolemia; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ezetimibe; Simvastatin
• Other Study ID Numbers: STUDY00001035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes