Anti-inflammatory Effects of Simvastatin

Inflammation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04638400
• Other study ID #: STUDY00001035
• Status: Terminated
• Phase: Phase 4
• Start date: May 1, 2017
• Est. completion date: November 1, 2021

Study information

• Verified date: December 2023
• Source: State University of New York at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: November 1, 2021
• Est. primary completion date: August 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Hypercholesterolemia
• Inflammation

Intervention

Drug:
• Simvastatin 40mg
Simvastatin administered daily for 6 weeks
• Ezetimibe 10mg
Ezetimibe administered daily for 6 weeks

Locations

Country	Name	City	State
United States	Diabetes and Endocrinology Research Center of WNY	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
paresh Dandona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mRNA Expression of CD68 in MNC	Percentage change in mRNA expression of CD68 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
Primary	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 will be calculated from data collected at 0 week and 6 weeks from starting study treatments.	6 weeks
Secondary	Change in mRNA Expression of IL-1ß in MNC	Percentage change in mRNA expression of IL-1ß 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
Secondary	Change in TNF-a mRNA Expression in MNC	Percentage change in mRNA expression of TNFa 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
Secondary	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