Effects of Statin and Ezetimibe Association on Kinetics of Artificial Chilomicrons

This study has been completed.
Sponsor:
Information provided by:
University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT00481351
First received: May 30, 2007
Last updated: January 7, 2011
Last verified: January 2007
  Purpose

Effects of statin and ezetimibe association on kinetics of artificial chylomicrons in men with stable coronary heart disease (CHD).

Background:

The rate (kinetics) of chylomicrons removal from circulation have been correlated with the incidence and severity of atherosclerotic lesions; a number of studies demonstrated lower plasmatic clearance of chylomicrons in patients with CHD compared to patients without this condition. It was also demonstrated a correlation among LDL-C levels and removal of chylomicrons remnants by a technique employing artificial chylomicrons.

The investigators also know that higher doses of more potent statins are more effective in chylomicrons removal than lower doses or less potent statins; nevertheless, the effect of the isolated use of statin has not been completely studied up to now.

Study design:

The investigators propose to study 26 outpatients volunteers with chronic CHD, followed at the Heart Institute - INCOR - of the School of Medicine, University of São Paulo.

Following a period of six weeks of washout from any cholesterol reducer, the kinetics of chylomicrons removal by a technique of emulsion of radiolabeled artificial chylomicrons will be evaluated. Lipid fractions, hepatic enzymes and CK will be measured. Initially patients will be randomly allocated to receive simvastatin 20 mg /day (n= 13) or ezetimibe 10 mg/day (n=13) for six weeks. At the end of this period, kinetics of chylomicrons removal and laboratorial measurements will be repeated (Period 1).

In the next period (Period 2) patients will receive simvastatin 20 mg/ ezetimibe 10 mg (n=13) or simvastatin 80 mg (n=13) for additional six weeks; at the end of this period, the evaluations will be repeated (third and last evaluation).

The aim of this study is to further understand chylomicrons metabolism in patients with chronic coronary disease receiving cholesterol reducers at different dosage regimes.


Condition Intervention Phase
Coronary Heart Disease
Drug: Simvastatin 20mg plus ezetimibe 10mg
Drug: ezetimibe
Drug: simvastatin 20mg
Drug: Simvastatin 80mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Statin and Ezetimibe Association on Kinetics of Artificial Chilomicrons in Men With Stable Coronary Heart Disease.

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:
  • Cholesteryl Ester Fractional Clearance Rate [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Low Density Lipoprotein [ Time Frame: 12week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Triglyceride Fractional Clearance Rate [ Time Frame: 6week ] [ Designated as safety issue: No ]
  • Alanine Aminotransferase [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • CPK [ Time Frame: 12 week ] [ Designated as safety issue: Yes ]
  • Total Cholesterol [ Time Frame: 12 week ] [ Designated as safety issue: No ]
  • High Density Lipoprotein [ Time Frame: 12 week ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: June 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: group1 ezetimibe
6 week wash out, followed by 06 week ezetimibe 10mg once a day e then 6 week ezetimibe 10mg plus sinvastatin 20mg for more 6 week.
Drug: Simvastatin 20mg plus ezetimibe 10mg
simvastatin 20mg plus ezetimibe 10mg once a day for 6 week.
Drug: ezetimibe
ezetimiba 10mg once a day
Active Comparator: group 2 simvastatin
6 week simvastatin 20mg once a day followed by 6 week simvastatin 80mg once a day.
Drug: simvastatin 20mg
simvastatin 20mg once a day
Drug: Simvastatin 80mg
simvastatin 20mg for 6week and then simvastatin 80mg for the next 6week.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stable coronary heart disease.

Exclusion Criteria:

  • Renal and Liver failure
  • Hypothyroidism
  • Diabetes mellitus
  • Neoplasia
  • Heart failure.
  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: NCT00481351

Sponsors and Collaborators
University of Sao Paulo
Investigators
Study Director: Raul D. Santos, Physician University of Sao Paulo
Principal Investigator: Otavio C. Mangili, Physician University of Sao Paulo
Study Chair: Raul C Maranhão, physician University of Sao Paulo
Study Chair: Ana Carolina M Gagliardi, nutritionist University of Sao Paulo
  More Information

No publications provided

Responsible Party: Otavio Celeste Mangili, MD, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT00481351     History of Changes
Other Study ID Numbers: 1068/06
Study First Received: May 30, 2007
Results First Received: January 7, 2011
Last Updated: January 7, 2011
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo:
artificial chilomicrons kinetics
ezetimibe plus statin
lipid lowering therapy

Additional relevant MeSH terms:
Heart Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Simvastatin
Ezetimibe
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 September 18, 2014