Clinical trial NCT04638400: Anti-inflammatory Effects of Simvastatin
Official title: Comparison of Effects of Simvastatin Versus Ezetimibe on Intracellular Lipid and Inflammation in Obese Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Inflammation
Atherosclerosis
Hypercholesterolemia
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
First posted: 2020-11-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in mRNA Expression of CD68 in MNC
timeFrame: 6 weeks
measure: Change in mRNA Expression of PECAM on MNC
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in mRNA Expression of IL-1β in MNC
timeFrame: 6 weeks
measure: Change in TNF-a mRNA Expression in MNC
timeFrame: 6 weeks
measure: Change in mRNA Expression of MMP-9 in MNC
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Diabetes and Endocrinology Research Center of WNY
state: New York
Study officials:
affiliation: Distinguished Professor of Medicine
name: Paresh Dandona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: