Official Title: “A Pilot Study of Treatment With Pegylated Interferon-Alpha2a, Ribavirin and Insulin Sensitizer Pioglitazone of Insulin Resistance (With the Exception of Diabetes) in Hepatitis C Virus Infection (The INSPIRED HCV Study)”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2007

Intervention(s) in this Clinical Trial

• Drug: Pioglitazone
  • Increase response to interferon alpha plus ribavirin by increasing insulin sensitivity
• Drug: Increase response to interferon alpha plus ribavirin by increasing insulin sensitivity
  • Pioglitazone 15 mg PD will be given to chronic hepatitis C patients in addition to peginterferon-alpha2a and ribavirin (Standard of Care, SOC) for 12 weeks to improve virological response. All recruited patients will be previous non-responders to SOC.

Primary Measures

• Early virological response
  • Time Frame: Week 12 of triple combined therapy
    Safety Issue?: Yes

Secondary Measures

• Undetectable serum HCV RNA after 4, 24 weeks and 48 weeks of therapy
  • Time Frame: Week 2, 24 and 48 of therapy
    Safety Issue?: Yes
• Changes (vs. baseline) of body weight, HOMA score, after 4, 12 and 48 weeks of therapy and after 24 weeks of follow-up
  • Time Frame: Weeks 4, 12 and 48 of therapy
    Safety Issue?: Yes
• Improvement (vs. baseline) of glucose tolerance parameters after 12 and 48 weeks of therapy and after 24 weeks of follow-up
  • Time Frame: Weeks 12 and 48 of therapy; week 24 of FU
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Hospital, Geneva

Overall Clinical Trial Officials and Contacts

Francesco Negro, Prof Principal Investigator University of Geneva, Switzerland  

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00433069

Study ID Number: GE-DMI-05-116

ClinicalTrials.gov Identifier: NCT00433069

Health Authority: Switzerland: Swissmedic