Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsored by: |
Department of Veterans Affairs |
---|---|
Information provided by: | Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00470262 |
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 proglitazone. 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. Th 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.
Condition | Intervention |
---|---|
Metabolic Syndrome X Prediabetic State |
Drug: Fenofibrate Drug: Pioglitazone and Fenofibrate |
Study Type: | Interventional |
Study Design: | Basic Science, Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study |
Official Title: | Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation in Subjects With Impaired Glucose Tolerance |
Estimated Enrollment: | 300 |
Study Start Date: | October 2007 |
Estimated Study Completion Date: | October 2010 |
Estimated Primary Completion Date: | October 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
1
Treatment with pioglitazone and fenofibrate in subjects with pre diabetes
|
Drug: Fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
Drug: Pioglitazone and Fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
|
2
Treatment with fenofibrate in subjects with pre diabetes
|
Drug: Fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
Drug: Pioglitazone and Fenofibrate
Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone
|
The correlation between obesity, inflammation and ectopic fat accumulation is wel 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.
Ages Eligible for Study: | 35 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Regina G Dennis, BA | RCDennis@uams.edu |
United States, Arkansas | |
Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock | Recruiting |
No. Little Rock, Arkansas, United States, 72114-1706 | |
Contact: Regina G Dennis, BA RCDennis@uams.edu | |
Principal Investigator: Neda Rasouli, MD |
Principal Investigator: | Neda Rasouli, MD | Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock |
Responsible Party: | Department of Veterans Affairs ( Rasouli, Neda - Principal Investigator ) |
Study ID Numbers: | ENDA-020-06S |
Study First Received: | May 4, 2007 |
Last Updated: | March 9, 2009 |
ClinicalTrials.gov Identifier: | NCT00470262 History of Changes |
Health Authority: | United States: Federal Government |
fatty acid oxidation complex fenofibrate Inflammation |
Peroxisome Proliferator-Activated Receptors pioglitazone Prediabetic State |
Antimetabolites Metabolic Syndrome X Metabolic Diseases Pioglitazone Antilipemic Agents Glucose Intolerance Prediabetic State Diabetes Mellitus Endocrine System Diseases Procetofen |
Cardiac Complexes, Premature Inflammation Abdominal Obesity Metabolic Syndrome Hyperinsulinism Hypoglycemic Agents Endocrinopathy Insulin Resistance Glucose Metabolism Disorders Metabolic Disorder |
Antimetabolites Metabolic Syndrome X Disease Metabolic Diseases Molecular Mechanisms of Pharmacological Action Pioglitazone Antilipemic Agents Physiological Effects of Drugs Prediabetic State Diabetes Mellitus Endocrine System Diseases |
Procetofen Pharmacologic Actions Inflammation Hyperinsulinism Hypoglycemic Agents Pathologic Processes Therapeutic Uses Syndrome Insulin Resistance Glucose Metabolism Disorders |