Anti-inflammatory Effects of Simvastatin

Phase 4

Terminated

• Conditions: Inflammation; Atherosclerosis; Hypercholesterolemia
• Interventions: Drug: Ezetimibe 10mg; Drug: Simvastatin 40mg

• Registration Number: NCT04638400
• Lead Sponsor: paresh Dandona

Brief Summary

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

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 Timeline

• Study Start: 2017-05-01
• Study First Submitted: 2020-10-07
• Study First Submitted QC: 2020-11-16
• Study First Posted: 2020-11-20
• Primary Completion: 2021-08-01
• Study Completion: 2021-11-01
• Results First Submitted: 2022-11-28
• Results First Submitted QC: 2023-12-28
• Results First Posted: 2024-01-23
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-11-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Ezetimibe	Ezetimibe 10mg	Obese subjects with elevated cholesterol
Simvastatin	Simvastatin 40mg	Obese subjects with elevated cholesterol

Primary Outcome Measures

Name	Time	Method
Change in mRNA Expression of CD68 in MNC	6 weeks	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.
Change in mRNA Expression of PECAM on MNC	6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in mRNA Expression of IL-1β in MNC	6 weeks	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
Change in TNF-a mRNA Expression in MNC	6 weeks	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
Change in mRNA Expression of MMP-9 in MNC	6 weeks	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

Trial Locations

Locations (1)

Diabetes and Endocrinology Research Center of WNY; 🇺🇸 Buffalo, New York, United States