Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance
Insulin resistance is common in people coinfected with HIV and Hepatitis C virus (HCV) and is associated with poor responses to treatment for HCV. Pioglitazone is an FDA-approved medication for the treatment of type 2 diabetes. It works by increasing the body's sensitivity to insulin. The purpose of this study is to determine whether treatment with pioglitazone prior to HCV treatment with peginterferon and ribavirin is safe and effective in improving the treatment outcome in insulin-resistant, HIV/HCV-coinfected people for whom previous treatment with peginterferon and ribavirin was unsuccessful.
HIV-1 and Hepatitis C Co-Infection
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Therapy With Pioglitazone Prior to HCV Treatment in HIV-1 and HCV Genotype 1-Infected Subjects With Insulin Resistance Who Are Prior Nonresponders to Peginterferon and Ribavirin Therapy|
- The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 24 of Step 2. [ Time Frame: Week 24 of Step 2 ] [ Designated as safety issue: No ]
- Safety and Tolerability [ Time Frame: Step 1 (Up to 24 to 28 weeks) ] [ Designated as safety issue: Yes ]Summary of the number of subjects with at least one grade 3 or higher sign/symptom or laboratory abnormality.
- Safety and Tolerability [ Time Frame: Step 2 (Up to 72 weeks) ] [ Designated as safety issue: Yes ]Summary of the number of subjects with at least one grade 3 or higher sign/symptom or laboratory abnormality.
- The Proportion of All Subjects With HCV Viral Load < 60 IU/mL at Week 72of Step 2. [ Time Frame: Week 72 of Step 2 ] [ Designated as safety issue: No ]
- Absolute Change From Entry to Week 24 of Step 1 in AST and ALT. [ Time Frame: From Entry to Week 24 of Step 1 ] [ Designated as safety issue: No ]
- Absolute Change From Entry to Week 24 of Step 1 in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) [ Time Frame: From Entry to Week 24 of Step 1 ] [ Designated as safety issue: No ]
- Absolute Change From Entry to Week 24 of Step 1 in Fasting Total Cholesterol and Triglycerides. [ Time Frame: From Entry to Week 24 of Step 1 ] [ Designated as safety issue: No ]
|Study Start Date:||March 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: PIO (step 1) then PIO+PEG-INF+RBV (step 2)
All participants in this study will receive pioglitazone therapy for 24 to 28 weeks. Participants will continue pioglitazone and add peginterferon and ribavirin to their treatment regimen for up to 48 additional weeks.
Traditionally used in the treatment of type 2 diabetes to increase insulin sensitivity. Participants will take 30 mg daily in tablet form.Drug: peginterferon
Used in the treatment of HCV. Participants will receive 180 mcg subcutaneously once a week.Drug: ribavirin
Used in the treatment of HCV. Participants will receive 1000 to 1200 mg orally per day depending on weight.
New and better strategies for the treatment of HCV in HIV/HCV-coinfected people are urgently needed. Standard therapy for HCV includes treatment with peginterferon plus ribavirin. Peginterferon is a modified form of the drug interferon and is used either alone or in combination with ribavirin for the treatment of HCV. Ribavirin works by stopping HCV from multiplying inside the body. Sustained virologic response rates in past large studies of peginterferon plus ribavirin used for treating HCV types 1 or 4 ranged from 11% to 29%. Studies have shown that insulin resistance in HCV-infected people who are HIV uninfected leads to poorer HCV treatment response. Improving the body's response to insulin may also improve the outcome of treatment for HCV.
Participants in this study will take pioglitazone alone for up to 28 weeks. At Entry and Weeks 2, 4, 8, 12,18, and 24 participants will receive clinical assessments. At Week 24, participants will undergo additional tests to ensure that they can enter Step 2 of the study. Participants who are able to continue will then take peginterferon and ribavirin in addition to the pioglitazone for up to 48 additional weeks. Clinical assessments will take place at the time of entry and Weeks 2, 4, 8, 12, 16, and 24 of Step 2. Participants who do not exhibit a response to the treatment at Weeks 12 or 24 will not continue Step 2, as it is unlikely that further treatment will elicit a response. Participants who continue in the study will return to the study site for clinical assessments at Weeks 32, 40, and 48 of Step 2. Follow-up visits will be held at Weeks 60 and 72. The assessments done at clinic visits may include any or all of the following tests: thyroid function, hematology and chemistry, fasting plasma glucose, liver function, gamma-glutamyl transferase, pregnancy, CD4/CD8, HIV-1 RNA, qualitative HCV RNA, and quantitative HCV RNA.
On November 18, 2011 the study was closed to accrual due to not meeting targeted accrual goals.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00665353
|United States, California|
|Ucsf Aids Crs (801)|
|San Francisco, California, United States, 94110|
|United States, Illinois|
|Northwestern University CRS (2701)|
|Chicago, Illinois, United States, 60611|
|United States, New Jersey|
|New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)|
|Newark, New Jersey, United States, 07103|
|United States, New York|
|Cornell CRS (7804)|
|New York, New York, United States, 10011|
|NY Univ. HIV/AIDS CRS (401)|
|New York, New York, United States, 10016|
|AIDS Care CRS (1108)|
|Rochester, New York, United States, 14642|
|United States, Ohio|
|Metro Health CRS (2503)|
|Cleveland, Ohio, United States, 44109|
|United States, Virginia|
|Virginia Commonwealth Univ. Medical Ctr. CRS (31475)|
|Richmond, Virginia, United States, 23219|
|Study Chair:||Marshall Glesby, MD, PhD||Cornell Clinical Trials Unit, Weill Medical College of Cornell University|
|Principal Investigator:||Kristen Marks, MD, MS||New York Presbyterian Hospital-Cornell|