HIV Clinical Trial
Official title:
Pioglitazone for Hepatic Steatosis in HIV/HCV Co-infection
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.
Status | Terminated |
Enrollment | 13 |
Est. completion date | January 2013 |
Est. primary completion date | January 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
- 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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
United States | VA Medical Center | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Jain MK, Skiest DJ, Cloud JW, Jain CL, Burns D, Berggren RE. Changes in mortality related to human immunodeficiency virus infection: comparative analysis of inpatient deaths in 1995 and in 1999-2000. Clin Infect Dis. 2003 Apr 15;36(8):1030-8. Epub 2003 Apr 2. — View Citation
Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis. 2000 Apr;30 Suppl 1:S77-84. Review. — View Citation
Sulkowski MS, Mehta SH, Torbenson M, Afdhal NH, Mirel L, Moore RD, Thomas DL. Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS. 2005 Mar 24;19(6):585-92. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Hepatic Steatosis and Hepatic Inflammation/Fibrosis in HIV/HCV Co-infected Patients With Steatosis. | Change in Hepatic Fat Content measured by MR spectroscopy: 48 weeks- Baseline | 48 weeks | No |
Secondary | Change in Insulin Resistance in HIV- and HCV-infected Patients With Steatosis Compared to Placebo | Change in Glucose Area Under the Curve from standard oral glucose challenge ( baseline to 2 hours): Week 48 - Baseline values | 48 weeks | No |
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