Pioglitazone to Treat Fatty Liver in Patients With HIV and Hepatitis C Infections
Condition: HIV; Hepatitis C; Liver Disease; Fatty Liver; Steatosis
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Liver Diseases; Fatty Liver
Intervention: Pioglitazone; Placebo
Intervention description: 45 mg/daily; one capsule daily
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: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: HIV; Hepatitis C; Liver Disease; Fatty Liver; Steatosis

Summary:

      This study will evaluate the effectiveness of pioglitazone in reducing liver fat content in
      patients with HIV and hepatitis C virus (HCV) infections. Fatty liver and accompanying
      insulin resistance in patients with HIV and HCV co-infections is associated with inflammatory
      changes, liver fibrosis and a poorer response to HCV treatment. Pioglitazone is a drug that
      helps to reduce the body's resistance to insulin. It is approved by the Food and Drug
      Administration to treat diabetes.

      Patients with HIV and HCV co-infections who have hepatic steatosis (fatty liver) may be
      eligible for this study. Candidates are screened with a medical history and physical
      examination, blood and urine tests, magnetic resonance imaging (MRI) of the liver to measure
      liver fat and, if needed, a liver biopsy to confirm the diagnosis of liver steatosis.

        -  Participants are randomly assigned to take either pioglitazone therapy or placebo for 48
           weeks. This is followed by a second 48-week treatment period in which all participants
           take pioglitazone.

        -  There are approximately 12 visits during the 96 weeks of the study. Participants will
           receive a physical assessment, blood and urine tests at each visit. In addition,
           periodic assessments of dietary habits, body composition, oral glucose tolerance
           testing, and health related quality of life questionnaires will be completed.

        -  A repeat MRI of the liver is performed at 48 weeks and at the end of the study to
           evaluate any potential changes in liver fat and inflammation. In addition, there is a
           follow-up liver biopsy at 48 weeks and an optional liver biopsy at 96 weeks.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Men and women, 18 years of age or greater

        Confirmed HIV infection by ELISA and Western blot

        No changes in antiretroviral regimen within the prior 3 months--Individuals not currently
        taking antiretroviral therapy will be eligible. Individuals requiring medically indicated
        adjustments of antiretroviral therapy during the course of the study will be eligible.

        Confirmed HCV infection, and no current or recent (within the past 3 months) HCV treatment
        and no plans to start HCV antiviral therapy in the foreseeable future.

        H-MRS liver fat content greater than 5 percent and confirmed steatosis on liver biopsy
        within 1 year

        Fasting glucose less than 126 mg/dL

        Platelets greater than or equal to 75,000/uL; INR less than 1.6

        Willingness to avoid medications and herbal supplements which may increase the risk of
        bleeding for one week prior to and one week following liver biopsy (e.g. aspirin,
        nonsteroidal anti-inflammatory drugs (NSAIDs), Vitamin E, fish oil and gingko biloba).

        Willingness to restrict physical activity 72 hours after liver biopsy

        If premenopausal female, willingness to use 2 forms of effective birth control on this
        study to avoid pregnancy.

        Have a primary care physician

        Willingness to have specimens stored.

        EXCLUSION CRITERIA:

        Current thiazolidinedione use or use in the last 6 months, known allergy or sensitivity to
        a thiazolidinedione

        Use of insulin or other oral hypoglycemics, or known diabetes

        Current pregnancy, breast feeding, or pregnancy within the past 6 months or desire to
        become pregnant within the next 2 years.

        Child-Pugh-Turcotte (CPT) score greater than class A

        ALT greater than 4 times the upper limit of normal

        Current or history of heart failure (New York Heart Association [NYHA] Class III or IV
        cardiac status)

        Hemoglobin level less than 9g/dL

        Active or ongoing infection with Hepatitis A or B

        Known or suspected liver disease such as autoimmune hepatitis, Wilson's disease,
        alpha-1-antitrypsin deficiency, cystic fibrosis, hemochromatosis, glycogen storage disease,
        amyloidosis, primary biliary cirrhosis, sclerosing cholangitis, or any primary or secondary
        hepatic tumor

        Current alcohol/substance abuse

        Use of growth hormone, prednisone or other anabolic agents (except for physiologic
        testosterone replacement) currently or within the past 3 months. One day or less of
        corticosteroid within the prior 90 days of screening is allowed as is stable dose
        inhalation corticosteroids

        Concurrent use of ketoconazole

        Active opportunistic infection (except thrush) or neoplasm (except Kaposi's sarcoma, skin
        cancer, cancer of the cervix or anus)

        Any known contraindications to percutaneous liver biopsy including elevated PT/PTT

        Severe psychiatric illness that would interfere with adherence to protocol requirements

        Current treatment with interleukin-2, interferon-alpha, or other investigational agent(s)
        within the past 6 months (This does not pertain to ARVs obtained through expanded access)

        Any significant medical condition for which the investigator believes a liver biopsy or
        participation in the research protocol may be contraindicated

        Any contraindication to MRI scan, including excess body size