Evaluation of Chylomicrons Metabolism in Sub-Clinical Atherosclerosis in Patients Whit Heterozigous Familial Hypercholesterolemia (FH) Treated With Statin Plus Ezetimibe

March 20, 2008 updated by: University of Sao Paulo

Study Title: Evaluation of chylomicrons metabolism in sub-clinical atherosclerosis in patients whit Heterozigous Familial Hypercholesterolemia (FH) treated with statin plus ezetimibe.

Background:

Coronary artery calcification (CAC) is a marker of sub-clinical coronary atherosclerosis which correlates with higher risk of clinical events. It was already demonstrated that CAC is more prevalent in patients with FH compared with normal individuals. A number of studies demonstrated that plasmatic removal of chylomicrons is defective in patients with atherosclerosis. Despite the fact that is still controversial whether this impairment occurs in patients with HF when compared to normal controls, the kinetics of chylomicrons has not been studied in HF patients with and without atherosclerosis and more important, it is not clear if those changes may be observed in the sub-clinical disease, as reported for CAC in asymptomatic individuals.

Previous studies have demonstrated the inverse correlation among LDL-C levels and the removal of remnants chylomicrons using artificial chylomicrons technique. It is also well known that high doses of more potent statins are more effective to remove chylomicrons from the plasma due to better expression of LDL-C receptors through plasma LDL-C reduction. It was not evaluated yet if the association of ezetimibe and statin, enhancing LDL-C receptors expression in the liver would enhance the efficacy of the monotherapy with statins to remove artificial chylomicrons in patients with HF.

Study design:

Open, randomized, single-blinded study in which twenty six outpatients from the Lipids Clinical Unit at the Heart Institute (INCOR), University of São Paulo, previously diagnosed with FH according to US MED PED criteria, without history of CD and a CAC evaluation by MSCT (Multiple Sensors Computed Tomography) in the previous year will be compared to 26 control individuals matched by age and sex collected from the database of the Lipids Metabolism Laboratory.

Patients will be randomized to receive simvastatin 40 mg as monotherapy or in combination with ezetimibe 10 mg and will undergoing three kinetics studies to demonstrate the effects of simvastatin 40 mg on the kinetics of the chylomicrons along with other laboratorial dosages ( lipid fractions, hepatic enzymes and CK).

The primary endpoint of this study is to evaluate if there is any correlation among the reduction of the plasma clearance of chylomicrons by the artificial chylomicrons technique and the presence of sub-clinical atherosclerosis; the secondary endpoint is to evaluate if ezetimibe/simvastatin enhances the effects of simvastatin alone in the removal of chylomicrons in patients with HF.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 05403-900
        • Recruiting
        • Heart Institute
        • Contact:
        • Principal Investigator:
          • Bruno Alcova Nogueira, MD
        • Sub-Investigator:
          • Raul Dias Santos Filho, Phd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Heterozigous Familial Hypercholesterolemia patients
  • Age 18 to 70
  • Male and Female
  • Coronary artery calcification

Exclusion Criteria:

  • Coronary artery disease
  • Cerebrovascular disease
  • Diabetes Mellitus
  • Heart Failure Class III-IV
  • Thyroid disease
  • Peripheral Artery disease
  • Pregnancy, women without anticonceptive method
  • Kidney disease or calcium disturbs
  • Thoracic Cancer
  • Use of Beta Blockers, diuretics, glucocorticoids ,hormone replacement therapy except oral anticonception
  • Use of lipid lowering drugs for the last six weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Evaluate if there is any correlation among the reduction of the plasma clearance of chylomicrons by the artificial chylomicrons technique and the presence of sub-clinical atherosclerosis
Time Frame: Five months
Five months

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluate if ezetimibe/simvastatin enhances the effects of simvastatin alone in the removal of chylomicrons in patients with HF.
Time Frame: Five Months
Five Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Bruno Alcova Nogueira, MD, Heart Institute-Universaty Of Sao Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Study Registration Dates

First Submitted

May 18, 2007

First Submitted That Met QC Criteria

May 18, 2007

First Posted (Estimate)

May 21, 2007

Study Record Updates

Last Update Posted (Estimate)

March 21, 2008

Last Update Submitted That Met QC Criteria

March 20, 2008

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1067/06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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