Effects of PPAR Ligands on Ectopic Fat Accumulation and Inflammation

NCT00470262 | Completed Results

• 2 other identifiers: ENDA-020-06S09-0710
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metabolic Syndrome X; Prediabetic State

Keywords

fatty acid oxidation complex; fenofibrate; Inflammation; Peroxisome Proliferator-Activated Receptors; pioglitazone; Prediabetic State; insulin resistance

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity

  Insulin sensitivity was measure through frequently sampled intravenous glucose tolerance test. Subjects presented to research center fasting. Blood samples were collected at -21, -11, and -1 minutes. At time t=0 initiates the start of the IVGTT and the injection of glucose into the non-sampling arm. The glucose dose was calculated as 11.4g/m2 of body surface area, given as a 50% dextrose solution. This glucose injection was administered over 60 seconds or less. At time t=20 minutes, an insulin dose of 0.04u/kg was administered over 30 seconds. Blood samples were collected at times t=2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 70, 90, 100, 120, 140, 160, and 180. If blood sugar did not return to a steady state the test was continued to t= 210 or t= 240.

  3 months

Secondary Outcomes (1)

• IMCL

  3 months

Study Arms (2)

Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD

OTHER

Treatment with pioglitazone and fenofibrate in subjects with pre diabetes

Drug: Fenofibrate 145mg PO QD; Drug: Pioglitazone 45 mg PO QD

Fenofibrate 145 mg PO QD

OTHER

Treatment with fenofibrate in subjects with pre diabetes

Drug: Fenofibrate 145mg PO QD

Interventions

Fenofibrate 145mg PO QD DRUG

Subjects will be randomized to either fenofibrates or combination of both fenofibrate and pioglitazone

Also known as: Tricor

Fenofibrate 145 mg PO QD; Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD

Pioglitazone 45 mg PO QD DRUG

Subjects will be randomized to either fenofibrate 145 mg PO QD or a combination of both fenofibrate 145 mg PO QD and pioglitazone 45 mg PO QD

Also known as: Actos

Fenofibrate 145 mg PO QD and Pioglitazone 45 mg PO QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Impaired glucose tolerance and/or impaired fasting glucose and/or metabolic syndrome
• Age 18-65
• BMI 28-38

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Eastern Colorado Health Care System, Denver

Denver, Colorado, 80220, United States

Location

Related Publications (1)

• Ipsen EO, Madsen KS, Chi Y, Pedersen-Bjergaard U, Richter B, Metzendorf MI, Hemmingsen B. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 19;11(11):CD013516. doi: 10.1002/14651858.CD013516.pub2.

  PMID: 33210751 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome; Prediabetic State; Inflammation; Insulin Resistance

Interventions

Fenofibrate; Pioglitazone

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Neda Rasouli
• Organization: Denver VA Medical Center

neda.rasouli@ucdenver.edu

303-399-8020

Study Officials

• Neda Rasouli, MD

  VA Eastern Colorado Health Care System, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2007
• First Posted: May 7, 2007
• Study Start: January 1, 2007
• Primary Completion: December 1, 2012
• Study Completion: June 1, 2014
• Last Updated: July 21, 2016
• Results First Posted: July 21, 2016

Record last verified: 2016-06

Locations

US (1)