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Sponsored by: |
Department of Veterans Affairs |
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Information provided by: | Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00108511 |
The purpose of this study is to examine the role of glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) in triglyceride metabolism.
Condition | Intervention | Phase |
---|---|---|
Hypertriglyceridemia |
Drug: Gemfibrozil |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Pharmacokinetics/Dynamics Study |
Official Title: | Effect of Gemfibrozil on Serum GPI Phospholipase D and Triglycerides |
Study Start Date: | October 2004 |
Estimated Study Completion Date: | September 2007 |
Increased fasting serum triglyceride levels are associated with an increased risk of coronary artery disease. However, triglyceride levels in the postprandial state are a more sensitive marker of coronary artery disease. Postprandial elevations in triglycerides result from a decrease in the catabolism of triglyceride-rich lipoproteins, i.e. chylomicrons and very low density lipoproteins (VLDL). This leads to an accumulation of atherogenic remnants of triglyceride-rich lipoproteins. Although fasting triglycerides are the best predictors of postprandial triglycerides, differences in fasting triglycerides only partially account for the variation in magnitude of postprandial triglycerides. Recently, we have identified a new protein involved in triglyceride-rich lipoprotein catabolism, glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). We have shown that elevated levels of GPI-PLD are associated with increased fasting triglyceride levels. Serum GPI-PLD is associated with high density lipoproteins (HDL) in the fasting state and exchange onto VLDL in the postprandial state. Hepatic GPI-PLD decreases triglyceride-rich lipoprotein catabolism in the liver. Hepatic and serum GPI-PLD levels are decreased by peroxisome proliferator receptor (PPAR) alpha agonist treatment, which also reduces fasting and postprandial triglycerides. The central hypothesis of this application is that variations in GPI-PLD expression account for a portion of the differences in fasting and postprandial triglycerides among humans.
The objective of this proposal is to determine the role of GPI-PLD in regulating fasting triglycerides and post-prandial hypertriglyceridemia in humans. This will be accomplished by conducting a double blind, placebo controlled study in humans examining the effect of gemfibrozil on fasting and postprandial triglycerides in relationship to the variation and changes in GPI-PLD before and after gemfibrozil.
Our specific objectives are:
This will be the first prospective bench-to-bedside study examining the role of GPI-PLD in triglyceride metabolism. This proposal will be the first in humans examining 1) the role of a novel protein, GPI-PLD, in triglyceride metabolism, and 2) the effect of gemfibrozil, a drug currently used clinically to lower triglyceride levels, on GPI-PLD levels in humans. It is expected that the results from this study will increase our understanding of triglyceride metabolism and develop new information in understanding the regulation of GPI-PLD and its relationship to triglyceride metabolism.
Ages Eligible for Study: | 19 Years to 74 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Study ID Numbers: | CLNB-009-04S |
Study First Received: | April 15, 2005 |
Last Updated: | March 27, 2008 |
ClinicalTrials.gov Identifier: | NCT00108511 |
Health Authority: | United States: Federal Government |
hypertriglyceridemia lipoproteins triglycerides serum GPI-PLD (glycosylphosphatidylinositol-specific phospholipase D) |
Gemfibrozil Metabolic Diseases Hyperlipidemias Hypertriglyceridemia |
Metabolic disorder Dyslipidemias Lipid Metabolism Disorders |
Antimetabolites Molecular Mechanisms of Pharmacological Action Therapeutic Uses Antilipemic Agents Pharmacologic Actions |