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| Sponsors and Collaborators: |
The University of Texas Health Science Center at San Antonio National Institutes of Health (NIH) Takeda Pharmaceuticals North America, Inc. |
|---|---|
| Information provided by: | The University of Texas Health Science Center at San Antonio |
| ClinicalTrials.gov Identifier: | NCT00227110 |
Purpose
To determine the role of pioglitazone in the treatment of nonalcoholic steatohepatitis (NASH) in patients with glucose intolerance or type 2 diabetes mellitus (T2DM).
| Condition | Intervention |
|---|---|
|
Non Alcoholic Steatohepatitis (NASH) |
Drug: pioglitazone |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study |
| Official Title: | Role of Pioglitazone in the Treatment of Non-Alcoholic Steatohepatitis (NASH) |
| Estimated Enrollment: | 120 |
| Study Start Date: | May 2001 |
| Estimated Study Completion Date: | September 2006 |
v. 4/1/2003 Role of Pioglitazone in the Treatment of Nonalcoholic Steatohepatitis
1. PURPOSE/SPECIFIC AIMS To determine the role of pioglitazone in the treatment of nonalcoholic steatohepatitis (NASH) in patients with glucose intolerance or type 2 diabetes mellitus (T2DM). NASH is a disease characterized by elevated plasma aminotransferases and histopathological changes in liver characterized by hepatocellular steatosis, chronic inflammation and fibrosis (1-3). Pioglitazone, a new thiazolidinedione (TZD), has proven to be safe and effective for the treatment of type 2 diabetes mellitus (T2DM) (4). NASH affects ~10-20% of obese and type 2 diabetic subjects (1-3, 5, 6). While the pathogenesis of NASH is poorly understood, there is consensus that insulin resistance and its associated abnormalities in lipid metabolism play a key role in the development of liver fat accumulation, and TNF-alpha is a major mediator in the progression of liver damage (7-9). Currently, there is no satisfactory therapy for NASH. Pioglitazone improves insulin sensitivity and glycemic control in patients with T2DM (4, 10-12), but the mechanism of action of TZDs is unclear (13, 14).
Pioglitazone activates genes involved in lipid synthesis, causing a reduction in plasma free fatty acid (FFA) and triglycerides (15). TZDs decrease excessive triglyceride accumulation in liver (16), muscle (17), and visceral fat (11, 16, 18), with a redistribution of fat to subcutaneous adipose stores (14). TZDs also antagonize the metabolic effects of TNF-alpha (19-22). Because pioglitazone ameliorates insulin resistance, reverses the metabolic abnormalities that contribute to hepatic fat infiltration (increased plasma glucose, FFA, and triglyceride concentrations), and antagonizes the effects of TNF-alpha, it follows that pioglitazone may prove useful for the treatment of patients with NASH.
In order to evaluate this hypothesis, we plan to treat for 6 months a group of patients with impaired glucose tolerance (IGT) or T2DM with pioglitazone in a randomized, double-blinded, placebo-controlled trial. Three major endpoints will be measured before and after treatment (see Methods for a detailed description):
Eligibility| Ages Eligible for Study: | 21 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Hemoglobin ≥ 13 gm/dl in males, or
Exclusion Criteria:
Contacts and Locations| Contact: Kenneth Cusi, MD | 2105676691 | cusi@uthscsa.edu |
| United States, Texas | |
| Audie L Murphy VA Hospital | Recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Bogdan Balas, MD 210-567-6741 balas@uthscsa.edu | |
| Principal Investigator: Kenneth Cusi, MD | |
| Principal Investigator: | Kenneth Cusi, MD | UTHSCSA |
More Information
| Study ID Numbers: | UTHSCSA IRB# 001-5014-331 |
| Study First Received: | September 23, 2005 |
| Last Updated: | January 3, 2006 |
| ClinicalTrials.gov Identifier: | NCT00227110 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
|
NASH, IGT, T2DM |
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Liver Diseases Hypoglycemic Agents Non-alcoholic Steatohepatitis (NASH) |
Digestive System Diseases Pioglitazone Fatty Liver |
|
Liver Diseases Hypoglycemic Agents Digestive System Diseases Pioglitazone |
Physiological Effects of Drugs Fatty Liver Pharmacologic Actions |