Ignite Creation Date:
2025-12-25 @ 3:38 AM
Ignite Modification Date:
2025-12-26 @ 2:23 AM
Study NCT ID:
NCT00327002
Status:
COMPLETED
Last Update Posted:
2015-12-11
First Post:
2006-05-15
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism
Sponsor:
University of Pennsylvania
Organization:
Study Overview
Official Title:
A Mechanistic Study of the Effects of LY518674 on HDL C Metabolism
Status:
COMPLETED
Status Verified Date:
2009-12
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:
Agents that increase HDL-C via reverse cholesterol transport could provide a new therapeutic option for the prevention of atherosclerotic cardiovascular disease. The investigators propose to investigate the effects of LY518674 on components that may likely affect atherogenesis in patients with the metabolic syndrome including HDL-C metabolism and reverse cholesterol transport pathways, the inflammatory response, and oxidative stress in human subjects.
As an agonist of the nuclear peroxisome proliferator activated receptor (PPAR) alpha, LY518674 may affect the transcription of genes that encode various proteins involved in atherogenesis. This study will explore the consequences of altered transcription such as changes in messenger ribonucleic acid (mRNA) and protein levels as well as protein activity.
As an agonist of the nuclear peroxisome proliferator activated receptor (PPAR) alpha, LY518674 may affect the transcription of genes that encode various proteins involved in atherogenesis. This study will explore the consequences of altered transcription such as changes in messenger ribonucleic acid (mRNA) and protein levels as well as protein activity.
Detailed Description:
Study Objectives
I. Primary Objective:
* To determine the effects of LY518674 on the Apo A-I production rate (calculated from the fractional synthetic rate and the fractional catabolic rate) in subjects with the metabolic syndrome and low HDL-C.
II. Secondary Objectives:
* To determine the effects of LY518674 on markers of reverse cholesterol transport by analyzing changes in serum cholesterol efflux capacity (an in vitro cell-based assay).
* To determine the effects of LY518674 on the activity of lecithin cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), lipoprotein lipase, hepatic lipase, and endothelial lipase.
* To determine the effects of LY518674 on plasma lipids, lipid subfractions, free fatty acids, and the free fatty acid metabolite, beta-OH butyrate.
* To determine the effects of LY518674 on high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particle size using nuclear magnetic resonance (NMR).
* To determine the effects of LY518674 on Apo A-II and Apo B-100 kinetics.
* To determine the effects of LY518674 on hsCRP.
* To determine the safety and tolerability of LY518674
Study Design:
Study H8D-MC-EMBG is a single site, randomized, placebo-controlled, double-blind, parallel study. A minimum of 40 subjects with low HDL cholesterol and metabolic syndrome will be randomized to receive double-blind administration of LY518674 100 mcg/day or placebo for 8 weeks. There is a safety visit every 2 weeks after treatment has been initiated, resulting in 7 visits over 10 weeks. There are 2 inpatient visits at zero and eight weeks.
I. Primary Objective:
* To determine the effects of LY518674 on the Apo A-I production rate (calculated from the fractional synthetic rate and the fractional catabolic rate) in subjects with the metabolic syndrome and low HDL-C.
II. Secondary Objectives:
* To determine the effects of LY518674 on markers of reverse cholesterol transport by analyzing changes in serum cholesterol efflux capacity (an in vitro cell-based assay).
* To determine the effects of LY518674 on the activity of lecithin cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), lipoprotein lipase, hepatic lipase, and endothelial lipase.
* To determine the effects of LY518674 on plasma lipids, lipid subfractions, free fatty acids, and the free fatty acid metabolite, beta-OH butyrate.
* To determine the effects of LY518674 on high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particle size using nuclear magnetic resonance (NMR).
* To determine the effects of LY518674 on Apo A-II and Apo B-100 kinetics.
* To determine the effects of LY518674 on hsCRP.
* To determine the safety and tolerability of LY518674
Study Design:
Study H8D-MC-EMBG is a single site, randomized, placebo-controlled, double-blind, parallel study. A minimum of 40 subjects with low HDL cholesterol and metabolic syndrome will be randomized to receive double-blind administration of LY518674 100 mcg/day or placebo for 8 weeks. There is a safety visit every 2 weeks after treatment has been initiated, resulting in 7 visits over 10 weeks. There are 2 inpatient visits at zero and eight weeks.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| GCRC # 0995 | None | None | View |