Effect of Crestor on Lipoprotein Metabolism in Humans
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.
Drug: Rosuvastatin at 5 mg/day and 40 mg/day
|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|
- Rate of production of VLDL apoB
- Rate of clearance of VLDL apoB
- Rate of production of LDL apoB
- Rate of clearance of LDL apoB
- Rate of production of HDL apoA-I
- Rate of clearance of HDL apoA-I
- Activity of cholesteryl ester transfer protein
|Study Start Date:||January 2005|
|Estimated Study Completion Date:||February 2006|
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.
|United States, Georgia|
|Atlanta Research and Education Foundation|
|Decatur, Georgia, United States, 30033|
|Principal Investigator:||Anh Le, PhD||Emory University School of Medicine and Atlanta VAMC|