To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects

Inflammation Clinical Trial

Official title:

To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01420328
• Other study ID #: MED7120311A
• Status: Completed
• Phase: N/A
• Start date: May 1, 2011
• Est. completion date: July 1, 2016

Study information

• Verified date: March 2024
• Source: University at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study focuses on the use of Vytorin to study inflammatory markers in subjects with normal cholesterol.

Description:

Following the first demonstration by our group that macronutrient (glucose, cream and a high fat high carbohydrate meal) intake results in increased ROS generation and oxidative stress at the cellular and molecular level, the investigators have now shown in our preliminary data that cream intake induces comprehensive inflammation as reflected in increased intranuclear NFkB binding, decreased IkBα expression, increased expression of IL-1β, IL-12, TNFα and other pro-inflammatory mediators. While carrying out these experiments, the investigators asked whether cream intake was associated with an uptake of lipid by peripheral blood mononuclear cells (MNC). Indeed, there was a significant increase in intracellular lipid which was visualized as intracellular lipid droplets. The increase in intracellular lipid droplets was associated with an increase in intracellular superoxide generation; the expression of CD68, a marker for macrophages; and PECAM, the adhesion molecule which mediates trans- endothelial transfer of leucocytes. The investigators also found that the lipid fractions to increase were cholesterol ester, triglyceride and fatty acids. In view of the tantalizing observation that the lipid droplet laden MNC appeared to be monocytes, looked like foam cells and the fact that CD68 expression had increased, there is a possibility that foam cells may be formed in peripheral circulation by monocytes after a lipid rich meal. This simple model of foam cell formation also lends itself for the study of the effect of various lipid lowering drugs. Our investigation will be the first to study this novel paradigm. The investigators plan to study the effect of a cholesterol lowering agent, Vytorin (simvastatin and ezetimibe), on intracellular lipid in MNC, expression of CD68 and PECAM, ROS generation and inflammation in obese subjects. This investigation may provide an additional mechanism of action by which these drugs may reduce atherosclerosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 1, 2016
• Est. primary completion date: July 1, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age 18-65years.

2. Obese BMI >30kg/m2

3. LDL cholesterol >100 mg/dl

4. Written and informed consent signed and dated 5. Not on any vitamin/antioxidants

Exclusion Criteria:

1. On any antilipid agents.

2. Triglyceride >500mg/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

• Inflammation

Intervention

Drug:
• Vytorin
Simvastatin 40 mg and Ezetimibe 10 mg daily combination pill (Vytorin) for 6 weeks
• Placebo
Placebo treatment for 6 weeks

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
University at Buffalo	Kaleida Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CD68 mRNA Expression in MNC	Percent change from baseline (0 week) in cream challenge induced change in CD68 mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo.; Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100	0 weeks and 6 weeks
Secondary	Change in Cream-induced Expression of CD16	Percent change from baseline (0 week) in cream -induced change in CD16 mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo.; Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100	6 weeks
Secondary	Change IL-1b mRNA Expression	Percent change from baseline (0 week) in cream -induced change in IL-1b mRNA expression in MNC after 6 weeks of treatment with Vytorin or placebo.; Outcome calculated as: (change at 6 weeks- change at 0 week)/ change at 0 week*100	6 weeks
Secondary	Change in Plasma Endotoxin (LPS) Concentrations	change from baseline (0 week) in cream -induced change in plasma endotoxin concentration after 6 weeks of treatment with Vytorin or placebo.; Outcome calculated as: (change at 6 weeks- change at 0 week)	6 weeks