Clinical trial NCT01420328: To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects
Official title: To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammation
Lead sponsor: University at Buffalo
Sponsor class: OTHER
Collaborators: name: Kaleida Health
First posted: 2011-08-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in CD68 mRNA Expression in MNC
timeFrame: 0 weeks and 6 weeks
Secondary outcomes:
measure: Change in Cream-induced Expression of CD16
timeFrame: 6 weeks
measure: Change IL-1b mRNA Expression
timeFrame: 6 weeks
measure: Change in Plasma Endotoxin (LPS) Concentrations
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Diabetes Endocrinology Center of WNY
state: New York
Study officials:
affiliation: University at Buffalo, NY
name: Paresh Dandona, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghanim H, Green K, Abuaysheh S, Patel R, Batra M, Chaudhuri A, Makdissi A, Kuhadiya ND, Dandona P. Ezetimibe and simvastatin combination inhibits and reverses the pro-inflammatory and pro-atherogenic effects of cream in obese patients. Atherosclerosis. 2017 Aug;263:278-286. doi: 10.1016/j.atherosclerosis.2017.06.010. Epub 2017 Jun 7.