Role of Pioglitazone in the Treatment of Non-alcoholic Steatohepatitis (NASH)

• Status: Completed
• Trial end date: 2006-01-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the role of pioglitazone in the treatment of nonalcoholic steatohepatitis (NASH) in patients with glucose intolerance or type 2 diabetes mellitus (T2DM).

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institutes of Health (NIH); Takeda Pharmaceuticals North America, Inc.
• Treatments: Pioglitazone

Criteria

Inclusion Criteria:

1. Be able to communicate meaningfully with the Investigator and be legally competent to provide written informed consent.

2. Patients must have an age range between 21 to 70 years (inclusive).

3. NASH confirmed by liver biopsy.

4. Subjects must meet the criteria for impaired glucose tolerance (FPG concentration <126 mg/dl and a two hour plasma glucose value during the oral glucose tolerance test [OGTT] ≥140 but <200 mg/dl) or type 2 diabetes mellitus (FPG concentration ≥ 126 mg/dl or a two hour plasma glucose value during the OGTT ≥200 mg/dl) (62). Subjects with a FPG greater than 260 mg/dl will be excluded from the study.

5. Diabetic patients will be allowed to be on sulfonylureas or repaglinide but not on metformin, a thiazolidinedione or insulin. Patients must have been on a stable dose of allowed chronic medications for four weeks prior to entering the double-blind treatment period.

6. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate mechanical contraceptive precautions (i.e. intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy are eligible for participation in the study. Female patients (except for those patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible only if they have a negative pregnancy test throughout the study period. Patients on oral contraceptives or an hormonal implant will be excluded.

7. All participants must have the following laboratory values:

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:

1. Any cause of chronic liver disease other than NASH (such as -but not restricted to- alcohol or drug abuse, medication, chronic hepatitis B or C, autoimmune, hemochromatosis, Wilson's disease, alpha1-antitrypsin deficiency).

2. Any clinical evidence or history of ascitis, bleeding varices, or spontaneous encephalopathy.

3. No past (for at least for 1 year) or current history of alcohol abuse (alcohol consumption greater than one drink per day).

4. Prior surgical procedures to include gastroplasty, jejuno-ileal or jejunocolic bypass.

5. Prior exposure to organic solvents such as carbon tetrachloride.

6. Total parenteral nutrition (TPN) within the past 6 months.

7. Diabetics with a FPG greater than 260 mg/dl on initial visit.

8. Diabetics who are taking metformin, a thiazolidinedione or insulin.

9. Subjects with type 1 diabetes mellitus.

10. Patients on chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on a stable dose of such agents for 4 weeks before entry into the study. Patients on estrogens or other hormonal replacement therapy, tamoxifen, raloxifene, oral glucocorticoids or chloroquine will be excluded.

11. Patients with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation), will not be studied.