Overview

This trial is active, not recruiting.

Conditions metabolic syndrome x, prediabetic state
Treatments fenofibrate, pioglitazone and fenofibrate
Sponsor Department of Veterans Affairs
Start date January 2007
End date December 2012
Trial size 300 participants
Trial identifier NCT00470262, 09-0710, ENDA-020-06S

Summary

The relationship between obesity and insulin resistance is known, however the mechanism(s) associating obesity with insulin resistance is not well understood. Inflammation and accumulation of fat in non fat tissue (like muscle) are conditions found on obesity which could be the potential link between obesity and insulin resistance. This study is designed to test the effects of two different drugs on numerous features of the obesity and insulin resistance in subjects with impaired glucose tolerance. Impaired glucose tolerance is a condition where blood sugar is too high after drinking a sugary drink containing 75 grams of sugar. Impaired glucose tolerant subjects are insulin resistant and at risk of developing diabetes. The drugs to be used are fenofibrate and pioglitazone. Fenofibrate is used to reduce the amount of fat (triglycerides) in the blood while pioglitazone is routinely used to make the body more sensitive to insulin in patients with diabetes. The purpose of this study is to compare the effects of either of these two medications (pioglitazone and fenofibrate) alone or the combination of both on fat accumulation in body (muscle) and inflammation. The amount of fat accumulation in muscle is thought to affect insulin sensitivity. In addition, the changes in the level of proteins produced by fat tissues will be studied in response to the two medications in this study. These proteins are thought to be involved in diabetes and insulin resistance.

These studies are designed to examine fundamental clinical mechanisms underlying the metabolic syndrome and diabetes.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose basic science
Arm
(Other)
Treatment with pioglitazone and fenofibrate in subjects with pre diabetes
fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
pioglitazone and fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
(Other)
Treatment with fenofibrate in subjects with pre diabetes
fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
pioglitazone and fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone

Primary Outcomes

Measure
Ectopic fat accumulation after 3 months of therapy
time frame: 3 months

Secondary Outcomes

Measure
Adipose tissue inflammation
time frame: 3 months

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Impaired glucose tolerance and/or impaired fasting glucose and/or metabolic syndrome - Age 18-65 - BMI 28-38 Exclusion Criteria: - Renal insufficiency: creatinine.1.4 - Liver disease: ALT.2x normal, congestive heart failure, history of documented coronary artery disease, concomitant use HMG CoA-reductase inhibitors (statins) - Concurrent use of ASA, steroids and other anti-inflammatory agents

Additional Information

Official title Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation in Subjects With Impaired Glucose Tolerance
Principal investigator Neda Rasouli, MD
Description The correlation between obesity, inflammation and ectopic fat accumulation is well recognized; however, the mechanism(s) responsible for obesity induced insulin resistance is not well understood. We will focus on lipotoxicity and inflammation as the link between obesity and insulin resistance. The factors leading to inflammation and ectopic lipid accumulation in obesity and the best intervention to reverse this pathophysiology are not clear. In this study, we will examine inflammation in adipose tissue and muscle lipid mechanism in response to Peroxisome Proliferator Activated Receptors (PPAR) and ligands have synergistic anti-inflammatory effects in adipose tissue and activation of PPAR and decrease muscle lipid oxidation and redistribution of lipid from muscle to adipocytes respectively. The combination of both medications will be particularly effective in reducing inflammation and muscle lipid accumulation. In this study, IGT subjects will be randomized to treatment with PPAR ligand (fenofibrate), PPAR ligand (pioglitazone) or combination of both for 10 weeks. Baseline studies will include assessment of body composition, insulin sensitivity, muscle and fat biopsies. All studies will be repeated after treatment with fenofibrate, pioglitazone or combination of both. Specific Aims (SA) are as follows: SA 1. Insulin sensitivity and Intramyocellular lipid (IMCL) from muscle biopsy specimens will be measured in response to different treatments (PPAR , and combination of both ligands). SA 2. The rate of fatty acid oxidation and the number of mitochondria in muscle will be measured in response to PPAR ligands. SA 3. The anti-inflammatory effects of PPAR and ligands will be studied by the measurement of the number of adipose tissue macrophages and the rate of macrophages apoptosis in fat biopsy specimens. In addition, the plasma levels and expression of proinflammatory proteins will be studied in response to different treatment. SA 4. The rate of SUMOylation of PPAR (a novel mechanism regulating anti-inflammatory effects of PPAR ligands) will be studied in response to PPAR , ligand or combination of both. These studies are designed to examine fundamental clinical mechanisms underlying the metabolic syndrome and diabetes. Potential Impact on Veterans Health Care: The national obesity/diabetes epidemic is magnified in the VA, and the cost of caring for these patients is enormous. This study will provide data on the mechanism of action of these drugs, which will improve our understanding of these drugs, impaired glucose tolerance, and treatment of metabolic syndrome. From the clinical perspective, this study uses drugs to treat patients with IGT, which is rapidly becoming recognized as a "disease" because of its association with coronary artery disease risk factors, and because of its high rate of progression to T2DM. If these drugs were shown to improve the care of patients, then they would eventually be a cost savings to the VA, either by choosing the less expensive drug, or by using the drug that delays the progression of the disease, and improves the care of the patient by preventing complications.
Trial information was received from ClinicalTrials.gov and was last updated in January 2014.
Information provided to ClinicalTrials.gov by Department of Veterans Affairs.