Effect of Crestor on Lipoprotein Metabolism in Humans

• ClinicalTrials.gov Identifier: NCT00214617
• Recruitment Status: Completed
• First Posted: September 22, 2005
• Last Update Posted: June 20, 2017
• Sponsor: Atlanta Research and Education Foundation
• Collaborator: AstraZeneca
• Information provided by: Atlanta Research and Education Foundation

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: Rosuvastatin at 5 mg/day and 40 mg/day	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Crestor on the Kinetics of Plasma Apolipoproteins: Dose-Response Study
• Study Start Date: January 2005
• Study Completion Date: February 2006

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Rate of production of VLDL apoB
2. Rate of clearance of VLDL apoB
3. Rate of production of LDL apoB
4. Rate of clearance of LDL apoB

Secondary Outcome Measures :

1. Rate of production of HDL apoA-I
2. Rate of clearance of HDL apoA-I
3. Activity of cholesteryl ester transfer protein

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• ClinicalTrials.gov Identifier: NCT00214617
• Other Study ID Numbers: AREF_Le_IRUSROSU 0021; IRUSROSU 0021
• First Posted: September 22, 2005
• Last Update Posted: June 20, 2017
• Last Verified: September 2006

Keywords provided by Atlanta Research and Education Foundation:

hypercholesterolemia; HMG CoA Reductase Inhibtors; tracer kinetics; Apolipoproteins

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Rosuvastatin Calcium; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors