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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Paresh Dandona, MD, Kaleida Health
ClinicalTrials.gov Identifier:
NCT01420328
First received: May 26, 2011
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

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


Condition Intervention Phase
Inflammation
Drug: Vytorin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: To Study the Effect of Vytorin on Intracellular Lipid and Inflammation in Obese Subjects

Resource links provided by NLM:


Further study details as provided by Kaleida Health:

Primary Outcome Measures:
  • Change in nile red staining score [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Change in nile red staining score of intracellular lipids following cream challenge before and after therapy with Vytorin


Secondary Outcome Measures:
  • Change in markers of monocyte activation [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Pecentage change in markers of monocyte activation; CD68 and PECAM expression following cream challenge before and after therapy with Vytorin .

  • Change in markers of inflammation [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Percentage change in expression of various markers of inflammation and oxidative stress such as NF-kB ,IkB Kinaseβ(IKKβ),IL-1β,IL-12,TNFα.

  • Change in the expression of toll like receptor [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Percentage change in expression of TLR-2, TLR-4, SOCS-3 and TRIF before and after treatment with vytorin


Estimated Enrollment: 20
Study Start Date: May 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Arm
Obese subjects with near normal cholesterol
Drug: Vytorin
Simvastatin 40 mg and Ezetimibe 10 mg daily combination pill (Vytorin
Other Name: Ezetimibi/Simvastatin 10/40
Active Comparator: Vytorin Arm
Obese subjects with near normal cholesterol
Drug: Vytorin
Simvastatin 40 mg and Ezetimibe 10 mg daily combination pill (Vytorin
Other Name: Ezetimibi/Simvastatin 10/40

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420328

Locations
United States, New York
Diabetes Endocrinology Center of WNY
Buffalo, New York, United States, 14209
Sponsors and Collaborators
Kaleida Health
Investigators
Principal Investigator: Paresh Dandona, MD University at Buffalo, NY
  More Information

No publications provided

Responsible Party: Paresh Dandona, MD, MD, Kaleida Health
ClinicalTrials.gov Identifier: NCT01420328     History of Changes
Other Study ID Numbers: MED7120311A
Study First Received: May 26, 2011
Last Updated: December 17, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014