Effect of Crestor on Lipoprotein Metabolism in Humans

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
Atlanta Research and Education Foundation
ClinicalTrials.gov Identifier:
NCT00214617
First received: September 19, 2005
Last updated: September 22, 2006
Last verified: September 2006
  Purpose

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.


Condition Intervention Phase
Hypercholesterolemia
Drug: Rosuvastatin at 5 mg/day and 40 mg/day
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Crestor on the Kinetics of Plasma Apolipoproteins: Dose-Response Study

Resource links provided by NLM:


Further study details as provided by Atlanta Research and Education Foundation:

Primary Outcome Measures:
  • 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:
  • Rate of production of HDL apoA-I
  • Rate of clearance of HDL apoA-I
  • Activity of cholesteryl ester transfer protein

Estimated Enrollment: 8
Study Start Date: January 2005
Estimated Study Completion Date: February 2006
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.

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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: NCT00214617

Locations
United States, Georgia
Atlanta Research and Education Foundation
Decatur, Georgia, United States, 30033
Sponsors and Collaborators
Atlanta Research and Education Foundation
AstraZeneca
Investigators
Principal Investigator: Anh Le, PhD Emory University School of Medicine and Atlanta VAMC
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00214617     History of Changes
Other Study ID Numbers: AREF_Le_IRUSROSU 0021, IRUSROSU 0021
Study First Received: September 19, 2005
Last Updated: September 22, 2006
Health Authority: United States: Food and Drug Administration

Keywords provided by Atlanta Research and Education Foundation:
hypercholesterolemia
HMG CoA Reductase Inhibtors
tracer kinetics
Apolipoproteins

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014