University of Texas H.S.C. San Antonio Pioglitazone in Non-Alcoholic Steatohepatitis Trial (UTHSCSA NASH Trial)

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Obesity and Type 2 diabetes are creating a silent epidemic, Non-alcoholic fatty liver disease, which is a chronic liver disease associated with insulin resistance, impaired glucose intolerance, and hepatic fat accumulation. The thiazolidinedione pioglitazone improves glucose/lipid metabolism and histology in NASH by improving insulin resistance in the liver/peripheral/adipose tissues and reducing subclinical inflammation. The aim of this study is to assess the underlying mechanisms at the clinical and molecular level and the long-term efficacy and safety of pioglitazone in NASH in a multiethnic cohort of subjects (predominantly Hispanics, Caucasians and African-Americans - the most common ethnic groups locally) and examine the response including patients with normal glucose tolerance, impaired glucose tolerance or established type 2 diabetes mellitus (T2DM).

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

Details

• Lead Sponsor: University of Florida
• Collaborator: The University of Texas at San Antonio
• Treatments: Pioglitazone

Criteria

Inclusion Criteria:

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

2. Age range between 18 to 70 years (inclusive).

3. Female patients must be non-lactating and must either be at least one year 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 (patches are acceptable as they deliver much lower estrogen systemically).

4. Participants must have the following laboratory values:

• Hemoglobin ≥ 12 gm/dl in males, or ≥ 11 gm/dl in females,

• WBC count ≥ 3,000/mm3

• Neutrophil count ≥ 1,500/mm3

• Platelets ≥ 100,000/mm3

• Albumin ≥3.0 g/dl

• Serum creatinine ≤ 1.8 mg/dl

• Creatinine phosphokinase ≤ 2 times upper limit of normal

• AST and ALT ≤ 3.0 times upper limit of normal

• Alkaline phosphatase ≤ 2.5 times upper limit of normal

5. A diagnosis of NASH by liver biopsy performed within the past 6 months,

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. Current history of alcohol abuse (alcohol consumption greater than 20 grams of ethanol 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. Subjects with type 1 diabetes mellitus.

8. 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.

9. Patients with a history of clinically significant heart disease (New York Heart Classification greater than grade II), peripheral vascular disease (history of claudication), or diagnosed pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation).

10. Patients with severe osteoporosis.