Effect of Crestor on Lipoprotein Metabolism in Humans

June 19, 2017 updated by: Foundation for Atlanta Veterans Education and Research, Inc.

Effect of Crestor on the Kinetics of Plasma Apolipoproteins: Dose-Response Study

The objective of this research is to understand how Crestor can effectively reduce the levels of the bad cholesterol, LDL, in blood. It is hypothesized that with a low dose, Crestor will facilitate the rate of removal of LDL from the blood. At the higher dose, the increased potency of Crestor is explained by a reduction in the production of LDL by the liver.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Crestor has been demonstrated to be effective in reducing plasma LDL by 20 to 60% in a dose dependent fashion. While the primary mechanism of action of this class of agents is the increase in the expression of LDL receptor resulting in accelerated clearance of LDL, the increase potency of Crestor in comparison to other statins may suggest other mechanisms. We propose to study the rate of incorporation of deuterated labeled leucine into VLDL apoB and LDL apoB and to determine the effect of two doses of Crestor (5 mg/day and 40 mg/day) on the production and clearance of apoB. Participants will be admitted to the General Clinical Research Center on three occasions (4 days, 3 nights per admission) for these metabolic studies. This is an open-label study design to reflect usual care with the first admission taking place while the participant is not on any lipid-lowering therapy. The second admission will occur after a minimum of 6 weeks on the low dose (5mg/day). The dose will be increased to 40 mg/day at the time of discharge and the third admission will occur after a minimum of 6 weeks on the higher dose.

A secondary objective of this study is to examine the rate of production and clearance of apoA-I, the major protein in HDL, at the 2 doses of Crestor. In addition to a reduction in LDL, Crestor has also been reported to result in a characteristic dose-dependent increase in HDL. The mechanism of this increase is not understood.

Study Type

Interventional

Enrollment

8

Phase

  • Phase 4

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

  • United States
    • Georgia
      • Decatur, Georgia, United States, 30033
        • Atlanta Research and Education Foundation

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

50 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • TG between 200 and 400 mg/dL
  • LDLc between 160 and 250 mg/dL
  • HDLc between 30 and 50 mg/dL for men and 40-65 mg/dL for women
  • Lp(a) less than 30 mg/dL
  • Age between 50 and 75 years

Exclusion Criteria:

  • current lipid-lowering therapy,
  • primary hypertriglyceridemia (TG>400 mg/dL),
  • High HDL (HDL>70),
  • high Lp(a), greater than 30 mg/dL
  • presence of beta-VLDL on agarose electrophoresis,
  • current use of immunosuppressive agents,
  • hormone replacement therapy for women
  • history of cancer, active liver disease or hepatic dysfunction (AST or ALT 1.5 x ULN (Upper Limit of Normal),
  • excessive consumption of alcohol, and recent history of drug abuse.

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

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Rate of production of VLDL apoB
Rate of clearance of VLDL apoB
Rate of production of LDL apoB
Rate of clearance of LDL apoB

Secondary Outcome Measures

Outcome Measure
Rate of production of HDL apoA-I
Rate of clearance of HDL apoA-I
Activity of cholesteryl ester transfer protein

Collaborators and Investigators

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

Sponsor

Foundation for Atlanta Veterans Education and Research, Inc.

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Anh Le, PhD, Emory University School of Medicine and Atlanta VAMC

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

January 1, 2005

Study Completion

February 1, 2006

Study Registration Dates

First Submitted

September 19, 2005

First Submitted That Met QC Criteria

September 19, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Actual)

June 20, 2017

Last Update Submitted That Met QC Criteria

June 19, 2017

Last Verified

September 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AREF_Le_IRUSROSU 0021
  • IRUSROSU 0021

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.

Clinical Trials on Hypercholesterolemia

Clinical Trials on Rosuvastatin at 5 mg/day and 40 mg/day

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in New Zealand

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe