Retreatment of Chronic Hepatitis C Non-responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone

• Status: Completed
• Trial end date: 2008-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to investigate the efficacy and safety of an insulin-sensitizer (Actos) added to a standard Pegasys/Copegus combination therapy of chronic hepatitis C in patients who have previously failed a pegylated-interferon-alpha / ribavirin combination without the insulin sensitizer. The primary endpoint is the initial virological response (level of HCV RNA in serum) as evaluated after 12 weeks of triple therapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Geneva
• Treatments: Insulin; Interferon alpha-2; Interferon-alpha; Interferons; Peginterferon alfa-2a; Pioglitazone; Ribavirin

Criteria

Inclusion Criteria:

• Histologically confirmed chronic hepatitis C as per liver biopsy performed during the 12 months prior to enrollment (except patients with histologically proven cirrhosis or a Actitest/Fibrotest assay, or a Fibroscan performed during the 12 months prior to enrollment)

• HCV RNA in serum >600 IU/ml

• elevated ALT

• HCV genotypes 1, 2, 3 or 4

• failure to respond to a prior treatment with a pegylated interferon alpha + ribavirin

• HOMA score > 2.00

• documentation that sexually active female patients of childbearing potential are practicing adequate contraception (intrauterine device, oral contraceptives, progesterone implanted rods, medroxyprogesterone acetate, surgical sterilization plus a barrier method [diaphragm + spermicide] or monogamous relationship with a male partner who has had a vasectomy or is using a condom + spermicide) during the treatment period and for 6 months after discontinuation of therapy. A serum pregnancy test obtained at entry prior to the initiation of treatment must be negative. Female patients must not be breast feeding

• documentation that sexually active male patients are practicing acceptable methods of contraception (vasectomy, use of a condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy

• willingness and capability to give written informed consent and to comply with the requirements of the trial

Exclusion Criteria:

• history of diabetes (ADA definition)

• history of significant cardiovascular disease (NYHA III) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure

• HBsAg and/or HIV

• auto-immune disease, including auto-immune hepatitis

• alcohol consumption exceeding 40 grams per day

• hepatocellular carcinoma

• renal insufficiency (serum creatinine levels above 200 micromol/l)

• unconjugated bilirubin blood level > 100 micromol/l

• glutamyl transferase > 20 times the ULN

• prothrombin time < 60% of control (except in case of oral anti-coagulant therapy)

• neutrophil count < 1.5 G/L

• platelet count < 70 G/L

• hemoglobin <120 g/L

• organ or bone marrow transplantation

• current neoplasm and/or anti-tumor chemotherapy

• current hepatic arterial thrombosis

• pregnant or breast feeding women; child bearing potential women without adequate contraception throughout the course of therapy

• psychosis or anti-depressant therapy for uncontrolled clinical depression

• epilepsy

• clinically significant retinal abnormalities

• thyroid dysfunction

• drug abuse or substitution therapy during the 12 months prior to inclusion

• interstitial pneumonitis

• previous auto-immune hemolysis and all causes of chronic hemolysis