University of Texas H.S.C. San Antonio Pioglitazone in Non-Alcoholic Steatohepatitis Trial (UTHSCSA NASH Trial)
Condition: Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver Disease; Type 2 Diabetes Mellitus
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Pioglitazone study drug; Placebo; Pioglitazone Open Label
Intervention description: 30 mg per day orally for 8 weeks, and if well tolerated, titrated to 45 mg per day until the end of 18 months; An oral tablet identical to pioglitazone will be given once daily but without active drug for 18 months.; Patients in both arms were placed open label pioglitazone for an additional 18 months after successfully completing the double-blind, placebo-controlled portion of the study design.
Intervention MeSH terms: Pioglitazone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 176.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Additional relevant MeSH terms:; Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Pioglitazone

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).
    

Eligibility 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.