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| Sponsor: | The University of Texas Health Science Center at San Antonio |
|---|---|
| Collaborators: |
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 | Phase |
|---|---|---|
|
Nonalcoholic Steatohepatitis |
Drug: Pioglitazone Drug: Placebo |
Phase IV |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Role of Pioglitazone in the Treatment of Non-alcoholic Steatohepatitis (NASH) |
| Enrollment: | 55 |
| Study Start Date: | October 2002 |
| Study Completion Date: | January 2006 |
| Primary Completion Date: | November 2005 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Pioglitazone
Pioglitazone 30 mg/d will be given for 8 weeks and titrated to 45 mg/d until the end of the 6-month study in a randomized, double-blind, study design.
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Drug: Pioglitazone
30 mg/d for 8 weeks and titrated to 45 mg/d until completing 6 months of treatment.
Other Name: Actos (Takeda Pharmaceuticals).
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Placebo Comparator: Placebo
Placebo once daily is given following a randomized, double-blind, placebo-controlled study design.
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Drug: Placebo
Placebo is given to match pioglitazone.
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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
≥ 12 gm/dl in females WBC count ≥ 3,000/mm3 Neutrophil count ≥ 1,500/mm3 Platelets ≥ 100,000/mm3 Prothrombin time within 3 seconds of control Albumin ≥3.0 g/dl Serum creatinine ≤ 1.6 mg/dl Creatinine phosphokinase ≤ 2 times upper limit of normal AST (SGOT) ≤ 2.5 times upper limit of normal ALT (SGPT) ≤ 2.5 times upper limit of normal Alkaline phosphatase ≤ 2.5 times upper limit of normal
Exclusion Criteria:
Contacts and Locations| United States, Texas | |
| Audie L Murphy VA Hospital | |
| San Antonio, Texas, United States, 78229 | |
| Principal Investigator: | Kenneth Cusi, MD | University of Texas |
More Information
| Responsible Party: | Kenneth Cusi, M.D., The University of Texas Health Science Center at San Antonio and the San Antonio VAMC. |
| ClinicalTrials.gov Identifier: | NCT00227110 History of Changes |
| Other Study ID Numbers: | UTHSCSA IRB# 001-5014-331 |
| Study First Received: | September 23, 2005 |
| Last Updated: | October 12, 2009 |
| Health Authority: | United States: Food and Drug Administration |
|
NASH, IGT, T2DM |
|
Fatty Liver Liver Diseases Digestive System Diseases Pioglitazone |
Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions |