Pioglitazone to Treat Fatty Liver in Patients With HIV and Hepatitis C Infections
|First Received Date ICMJE||August 26, 2008|
|Last Updated Date||April 2, 2014|
|Start Date ICMJE||August 2008|
|Primary Completion Date||January 2013 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To determine the efficacy of pioglitazone to reduce hepatic steatosis and possibly improve hepatic inflammation/fibrosis in HIV/HCV co-infected patients with steatosis. [ Time Frame: 48 weeks and 96 weeks ] [ Designated as safety issue: Yes ]|
|Original Primary Outcome Measures ICMJE
||To determine the efficacy of pioglitazone to reduce hepatic steatosis and possibly improve hepatic inflammation/fibrosis in HIV/HCV co-infected patients with steatosis.|
|Change History||Complete list of historical versions of study NCT00742326 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To assess the effects of pioglitazone on insulin resistance in HIV- and HCV-infected patients with steatosis compared to placebo and to evaluate the potential relationship between improvements in steatosis and changes in insulin resistance in th... [ Time Frame: 48 weeks and 96 weeks ] [ Designated as safety issue: Yes ]|
|Original Secondary Outcome Measures ICMJE
||To assess the effects of pioglitazone on insulin resistance in HIV and HCV-infected patients with steatosis compared to placebo and to evaluate the potential relationship between improvements in steatosis and changes in insulin resistance in this set.|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Pioglitazone to Treat Fatty Liver in Patients With HIV and Hepatitis C Infections|
|Official Title ICMJE||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.
Following the introduction of effective antiretroviral therapy for HIV, the management of co-morbidities such as hepatitis C virus (HCV) has taken on increasing significance in the care and health maintenance of chronically infected patients. HCV co-infection is common in HIV, with an estimated prevalence of 30 percent among HIV-infected adults in the US. Further, the reported prevalence of hepatic steatosis in HIV/HCV co-infection is between 40-67 percent.
In recent years, the significance of hepatic steatosis and accompanying insulin resistance in HCV has gained increasing recognition. For example, steatosis is associated with increased rates of necro-inflammatory change and fibrosis in HIV/HCV co-infected patients. Furthermore, studies showed that, among non-HIV infected HCV patients, the presence of steatosis and/or insulin resistance was associated with poorer response to HCV therapy. These observations have led to research interest in treating hepatic steatosis in HCV, particularly in the context of pegylated interferon and ribavirin therapy.
Administration of the thiazolidinedione, pioglitazone, leads to significant reductions in hepatic steatosis, inflammation and in some cases fibrosis in patients with non-alcoholic steatohepatitis (NASH). Therefore, the potential benefits of pioglitazone therapy in the setting of HIV/HCV co-infection and hepatic steatosis will be determined. The proposed study is a 48-week, double-blind, randomized placebo-controlled trial of pioglitazone (45 mg/day) in 50 HIV/HCV-infected men and women. After the 48-week randomized portion of the trial, all participants will enter a 48-week open treatment extension arm irrespective of original randomization. It is anticipated that 100 subjects will be needed to be screened to identify a sufficient number of eligible participants to enroll in the study.
The primary outcome variable of interest in this trial will be the change in hepatic fat content measured by magnetic resonance (MR) spectroscopy. Important secondary outcomes will be histologic improvement on liver biopsy performed at baseline and 48 weeks, as well as improvements in transaminase levels and insulin resistance. The open treatment extension will allow all participants an opportunity to receive active study medication and it will allow the potential benefits of additional pioglitazone therapy to be assessed. In this way, important information about the efficacy of pioglitazone to treat hepatic steatosis and improve the metabolic profile in HIV/HCV co-infected patients will be obtained.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Pioglitazone
|Study Arm (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Completion Date||December 2014|
|Primary Completion Date||January 2013 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
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.
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
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00742326|
|Other Study ID Numbers ICMJE||080201, 08-I-0201|
|Has Data Monitoring Committee||Yes|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP