Ignite Creation Date:
2024-05-05 @ 4:49 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00317993
Status:
COMPLETED
Last Update Posted:
2014-12-03
First Post:
2006-04-24
Brief Title:
LDL Receptor Under Ezetimibe and Simvastatin
Sponsor:
University of Cologne
Organization:
University of Cologne
Study Overview
Official Title:
Effects of Ezetimibe and Simvastatin on LDL Receptor Protein Expression and on LDL Receptor and HMG-CoA Reductase mRNA Expression in Mononuclear Cells a Randomized Controlled Study in Healthy Men
Status:
COMPLETED
Status Verified Date:
2014-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to investigate the effects of the two lipid -lowering drugs ezetimibe and simvastatin on lipid metabolism in humans In specific the study will investigate in blood cells whether the enzyme that controls cholesterol synthesis HMG-CoA reductase and the receptor that takes up cholesterol from the blood the LDL receptor are changed during treatment with the aforementioned drugs
Detailed Description:
Ezetimibe decreases serum total and LDL cholesterol levels by blocking cholesterol absorption in the intestine causing a compensatory increase in cholesterol synthesis The exact underlying regulatory mechanisms of the ezetimibe-induced increase in cholesterol synthesis and decrease in serum LDL cholesterol are not known In addition it has never been investigated whether changes in LDL receptor expression contribute to the LDL-lowering effect of ezetimibe as is the case with other agents causing a decrease in cholesterol absorption such as the plant stanols
In the present study we plan to examine changes in LDL receptor and HMG-CoA reductase mRNA concentrations during ezetimibe treatment For comparison effects of simvastatin and the combined administration of the two will be investigated Since mRNA expression profiles provide information about effects at the transcriptional but not necessarily at the translational level we will also analyze changes in the LDL receptor protein at the cell surface of mononuclear blood cells As a functional marker for HMG-CoA reductase activity the ratio of serum lathosterol to cholesterol concentration will be used since it correlates with HMG-CoA reductase activity and serves also as a marker of total cholesterol synthesis
In this regard it has been shown that plant sterols which also act by blocking intestinal cholesterol absorption increase cholesterol synthesis decrease LDL synthesis increase LDL receptor mRNA levels as well as LDL receptor protein concentrations but have no significant effect on HMG-CoA reductase expression or activity in peripheral blood mononuclear cells Aim of this prospective ran-domized parallel study is to examine changes in HMG-CoA reductase activityexpression and in LDL receptor expressionprotein concentration in mononuclear blood cells under treatment with ezetimibe
For this purpose 3 parallel groups of 20 healthy men will be formed One group will be treated with ezetimibe 10 mgday one with 40 mgday of simvastatin and another with ezetimibe 10 mgday plus simvastatin 40 mgday Each treatment period will last for 2 weeks Blood drawing will be per-formed at baseline before the initiation of treatment and at the end of the 2 weeks storing of the samples at -80 The measurements involved in this study include the determination of the lipopro-tein concentrations in serum isolation of the mononuclear cells measurement of LDL receptor mRNA from the peripheral blood mononuclear cells measurement of HMG-CoA reductase mRNA levels in peripheral blood mononuclear cells measurement of the LDL-receptor protein concentrations on the surface of peripheral blood mononuclear cells Furthermore the serum latosterol to cholesterol con-centrations will be measured as a surrogate marker of the HMG-CoA reductase activity
In the present study we plan to examine changes in LDL receptor and HMG-CoA reductase mRNA concentrations during ezetimibe treatment For comparison effects of simvastatin and the combined administration of the two will be investigated Since mRNA expression profiles provide information about effects at the transcriptional but not necessarily at the translational level we will also analyze changes in the LDL receptor protein at the cell surface of mononuclear blood cells As a functional marker for HMG-CoA reductase activity the ratio of serum lathosterol to cholesterol concentration will be used since it correlates with HMG-CoA reductase activity and serves also as a marker of total cholesterol synthesis
In this regard it has been shown that plant sterols which also act by blocking intestinal cholesterol absorption increase cholesterol synthesis decrease LDL synthesis increase LDL receptor mRNA levels as well as LDL receptor protein concentrations but have no significant effect on HMG-CoA reductase expression or activity in peripheral blood mononuclear cells Aim of this prospective ran-domized parallel study is to examine changes in HMG-CoA reductase activityexpression and in LDL receptor expressionprotein concentration in mononuclear blood cells under treatment with ezetimibe
For this purpose 3 parallel groups of 20 healthy men will be formed One group will be treated with ezetimibe 10 mgday one with 40 mgday of simvastatin and another with ezetimibe 10 mgday plus simvastatin 40 mgday Each treatment period will last for 2 weeks Blood drawing will be per-formed at baseline before the initiation of treatment and at the end of the 2 weeks storing of the samples at -80 The measurements involved in this study include the determination of the lipopro-tein concentrations in serum isolation of the mononuclear cells measurement of LDL receptor mRNA from the peripheral blood mononuclear cells measurement of HMG-CoA reductase mRNA levels in peripheral blood mononuclear cells measurement of the LDL-receptor protein concentrations on the surface of peripheral blood mononuclear cells Furthermore the serum latosterol to cholesterol con-centrations will be measured as a surrogate marker of the HMG-CoA reductase activity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None