Effect of Gemfibrozil on Serum Glycosylphosphatidylinositol (GPI) Phospholipase D and Triglycerides

This study has been completed.
Sponsor:
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00108511
First received: April 15, 2005
Last updated: January 20, 2009
Last verified: May 2007
  Purpose

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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effect of Gemfibrozil on Serum GPI Phospholipase D and Triglycerides

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Study Start Date: October 2004
Estimated Study Completion Date: September 2007
Detailed Description:

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:

  • 1a) Determine the extent to which variations in GPI-PLD account for differences in fasting and postprandial triglycerides
  • 1b) Establish the degree to which the lowering of fasting and postprandial triglycerides by gemfibrozil is accounted for by changes in GPI-PLD.
  • 2) Quantify the changes in serum GPI-PLD and distribution of GPI-PLD among lipoproteins in the postprandial state.

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.

  Eligibility

Ages Eligible for Study:   19 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age >18 and <75
  • Fasting triglycerides >150 mg/dl

Exclusion Criteria:

  • Fasting triglycerides >600 mg/dl
  • LDL >130 mg/dl
  • Concurrent lipid lowering therapy
  • Known hypersensitivity to gemfibrozil
  • Alcohol intake >30 gm/day (2 drinks/day)
  • Fasting glucose >125 mg/dl or known type 2 diabetes
  • AST or ALT > 2.0 x upper limit of normal
  • Creatinine: men >1.4 mg/dl, women >1.3 mg/dl
  • Cancer treatment in the past 5 years (unless cured)
  • Infectious diseases including HIV or tuberculosis
  • Significant cardiac disease in the past 6 months (myocardial infarction, coronary artery bypass graph, angioplasty, class 3 or 4 congestive heart failure, left bundle branch block, third degree AV block)
  • Uncontrolled hypertension (systolic blood pressure [SBP] >180 or diastolic blood pressure [DBP] > 105 mm Hg)
  • Anemia (hematocrit <40% men, <35% women)
  • Any other significant systemic disease or medication that could interfere with tolerance of medication or outcome
  • Any indication that a participant will be unable to adhere to the protocol
  • Unable to give informed consent
  • Pregnant or breastfeeding females or a female who plans to become pregnant while participating in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00108511

Locations
United States, Indiana
Roudebush VA Medical Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00108511     History of Changes
Other Study ID Numbers: CLNB-009-04S
Study First Received: April 15, 2005
Last Updated: January 20, 2009
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
hypertriglyceridemia
lipoproteins
triglycerides
serum GPI-PLD (glycosylphosphatidylinositol-specific phospholipase D)

Additional relevant MeSH terms:
Hypertriglyceridemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Gemfibrozil
Antimetabolites
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014