The effect of peroxisome proliferator activator receptor γ agonist pre-treatment on pegylated interferon-α2a and ribavirin efficacy in hepatitis C patients, previously resistant to treatment with pegylated interferon and ribavirin

INTERVENTION: Trade Name: Actos Pharmaceutical Form: Capsule* Pharmaceutical form of the placebo: Capsule* Route of administration of the placebo: Oral use Trade Name: Pegasys Pharmaceutical Form: Injection* Product Name: Copegus Pharmaceutical Form: Coated tablet CONDITION: Chronic hepatitis C infection ; MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C PRIMARY OUTCOME: Main Objective: To study the effect of a 16‐week treatment with PPAR‐? agonist versus placebo on the effectiveness of subsequent standard treatment with PEG‐IFN and RBV on disease activity, measured as SVR, in previously non‐responding or relapsing CHC genotype 1 patients. Primary end point(s): The primary outcome measure, the responsiveness to antiviral therapy of previously non‐responding and relapsing CHC patients genotype 1, is expressed as the portion of participants with SVR in the PPAR‐? treated and placebo group. SVR is defined as undetectable serum HCV‐RNA 6 months after completing PEG‐IFN‐a2a and RBV therapy. Secondary Objective: Secondary objectives are to study associations of disease activity, liver fat content, liver function, liver histomorphology, insulin sensitivity and response to antiviral therapy INCLUSION CRITERIA: ? CHC genotype 1 infected men and women = 21 and = 65 yrs of age ? Previously non‐responders or relapsers to PEG‐IFN and RBV containing treatment ? Previous resistance to antiviral therapy will be defined as: ‐ Decrease in PCR detected viral load of =2log in response to at least 12 weeks of treatment with PEG‐IFN and RBV containing treatment ‐ Recurrence of HCV‐RNA, previously undetectable after treatment of at least 12 weeks with PEG‐IFN and RBV containing treatment (breakthrough and relapse) ? Patients requiring a liver biopsy before treatment ? Fasting plasma glucose =7.0 mmol/l ? Hepatic steatosis defined as increased hyperechogenicity on abdominal ultrasound and/or histological signs of steatosis (grade 0‐3 according to the NASH clinical research network scoring system) ? Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 ye