Pioglitazone Before Peginterferon and Ribavirin for Hepatitis C Infection in HIV/HCV-Coinfected Patients With Insulin Resistance
Condition: HIV-1 and Hepatitis C Co-Infection
MeSH terms: Infections; Hepatitis A; Hepatitis C; Coinfection; Hepatitis; Insulin Resistance
Intervention: pioglitazone; peginterferon; ribavirin
Intervention description: Traditionally used in the treatment of type 2 diabetes to increase insulin sensitivity. Participants will take 30 mg daily in tablet form.; Used in the treatment of HCV. Participants will receive 180 mcg subcutaneously once a week.; Used in the treatment of HCV. Participants will receive 1000 to 1200 mg orally per day depending on weight.
Intervention MeSH terms: Pioglitazone; Ribavirin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HCV

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

        For Step 1:

          -  HIV infected

          -  Exhibited no response to previous treatment with PEG-IFN alfa-2a 180 mcg/week or
             alfa-2b 1.5 mcg/kg/week and at least 1000 mg/day ribavirin given for at least 12
             consecutive weeks. More information on this criterion can be found in the protocol.

          -  HOMA-IR valued greater than 2.5 within 42 days prior to study entry. More information
             on this criterion can be found in the protocol.

          -  CD4 count of at least 200 cells/mm3 within 42 days prior to study entry

          -  HCV RNA of at least 60 IU/ml by quantitative RT-PCR assay with or without reactive
             anti-HCV antibodies within 42 days prior to study entry

          -  Documentation of infection with HCV genotype 1, within 42 days prior to study entry

          -  On stable or no antiretroviral therapy for 12 weeks prior to study entry.
             Interruptions in treatment lasting 14 days or less are allowed if the participant
             reinitiated the same regimen prior to study entry. Dose modifications or changes in
             drug formulations during the 12 weeks prior to study entry are permissible.

          -  Participants on antiretroviral therapy should plan to remain on the same therapy for
             at least 24 weeks after study entry. Participants not on antiretroviral therapy should
             have no plans to initiate therapy during the first 24 weeks following study entry.

          -  Participants with documented or suspected hepatic cirrhosis must have a modified
             Child-Pugh-Turcotte (CPT) within 42 days prior to study entry.

          -  Participants with documented or suspected hepatic cirrhosis must have either serum
             alpha-fetoprotein level of 50 ng/ml or less within 24 weeks prior to study entry; OR
             serum alpha-fetoprotein greater than 50 ng/ml but no greater than 400 ng/ml with an
             imaging procedure that shows no evidence of a hepatic tumor, both obtained within 24
             weeks prior to study entry.

          -  Certain laboratory values obtained within 42 days prior to study entry. More
             information on this criterion can be found in the protocol.

          -  Willing to use effective forms of contraception throughout the study. More information
             on this criterion can be found in the protocol.

          -  Ability and willingness of participant to give written informed consent.

        For Step 2:

          -  No more than 28 days have passed since the Step 1, Week 24 visit

          -  Participants who were treated in Step 1 who meet the following criteria:

               1. Detectable HCV RNA (> 60 IU/mL) at the Step 1, Week 24 evaluation

               2. CD4 cell count of at least 200 cells/mm3 at Week 24. If the CD4 count is less
                  than 200 cells/mm3 at Week 24, then it must not have decreased by more than 20
                  cells/mm3 from the Step 1 entry value.

               3. Taking pioglitazone at the time of Step 2 entry

          -  Certain laboratory values obtained within 28 days prior to Step 2 entry. More
             information on this criterion can be found in the protocol.

          -  Willing to use an effective form of contraception throughout the study

          -  Female participants of reproductive potential are required to have a negative serum or
             urine β-HCG pregnancy test within 14 days prior to Step 2 entry

          -  Participants without a pregnant partner.

        Exclusion Criteria:

          -  Presence of known causes of significant liver disease. More information on this
             criterion can be found in the protocol.

          -  Evidence of decompensated liver disease manifested by presence or history of ascites,
             variceal bleeding, or hepatic encephalopathy

          -  History of HCV treatment within 28 days prior to study entry

          -  Evidence that nonresponse to prior HCV treatment may have been due to nonadherence or
             certain dose reductions. More information on this criterion can be found in the
             protocol.

          -  Use of interferon gamma, TNF-alpha inhibitors, rifampin, rifabutin, pyrazinamide,
             isoniazid, ganciclovir, or hydroxyurea within 14 days prior to study entry

          -  Current use of didanosine or zidovudine or plans to initiate use of either during the
             study

          -  Active drug or alcohol abuse or dependence that, in the opinion of the study
             investigator, could interfere with adherence to study requirements

          -  History of uncontrolled seizure disorder

          -  Uncontrolled depression or other psychiatric disorder, such as untreated Grade 3
             psychiatric disorder, Grade 3 disorder not amenable to medical intervention, or any
             hospitalization within the past 52 weeks that may affect tolerability of study
             requirements

          -  History of autoimmune disorders, including but not limited to Crohn's disease,
             ulcerative colitis, severe psoriasis, and rheumatoid arthritis, that have been
             exacerbated by previous interferon use

          -  Any systematic antineoplastic or immunomodulatory treatment or radiation within 24
             weeks prior to study entry

          -  Serious illness including malignancy, active symptomatic coronary artery disease
             within 24 weeks prior to study entry, or other chronic medical condition that could
             interfere with safe study completion

          -  Presence of AIDS-defining opportunistic infections within 12 weeks prior to study
             entry

          -  Hemoglobinopathy (e.g., thalassemia major) or any other cause of or tendency to
             hemolysis. Subjects with thalassemia minor may be enrolled at the discretion of the
             investigator.

          -  History of major organ transplantation with an existing functional graft

          -  Use of antidiabetic medications for any reason within 12 weeks prior to study entry

          -  Fasting plasma glucose level of at least 126 mg/dl within 42 days prior to study entry
             or current or previous treatment at any time for diabetes with measures other than
             diet. Women with a history of gestational diabetes, patients with diabetes or
             hyperglycemia occurring in the context of short term use of corticosteroids, growth
             hormone, or other diabetogenic medication, and patients with diabetes or hyperglycemia
             following an episode of pancreatitis who no longer require treatment for diabetes are
             not excluded.

          -  Known osteoporosis or receipt of treatment of osteopenia or osteoporosis within 12
             weeks prior to study entry with the following medications: risedronate (Actonel®),
             ibandronate (Boniva®), etidronate (Didronel®), raloxifene (Evista®), teriparatide
             (Forteo®), aledronate (Fosamax®), calcitonin (Miacalcin®).

          -  Known initiation or change in dose of any statins, fibrates, omega-3 fatty acids, bile
             acid sequestrants, ezetimibe, and niacin derivatives within 12 weeks prior to study
             entry

          -  Known allergy, sensitivity, or hypersensitivity to components of the study drugs or
             their formulation

          -  Regular and excessive use of alcohol within the 12 weeks prior to study entry. More
             information on this criterion can be found in the protocol.

          -  Unwilling to restrict alcohol use during the study to 120 g of alcohol per week or
             less for men and 60 g of alcohol per week or less for women

          -  Known glucocorticoid use in supraphysiologic doses (e.g., more than 10 mg per day of
             prednisone or equivalent doses of other glucocorticoids) within 12 weeks prior to
             study entry

          -  Known glucocorticoid use in physiologic replacement doses (e.g., 10 mg or less per day
             of prednisone or equivalent doses of other glucocorticoids) initiated within 28 days
             prior to study entry

          -  History of congestive heart failure corresponding to New York Heart Association Class
             II or greater

          -  Current use of prohibited concomitant medications. More information on this criterion
             is available in the protocol.

          -  Current participation in experimental studies that include treatments not approved by
             the FDA or any blinded treatments, with the exception of investigational
             antiretrovirals available through expanded access programs

          -  Body mass index (BMI) greater than 35 kg/m2

          -  Participant or participant's partner is pregnant or breastfeeding