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

Condition(s) targeted: Chronic Hepatitis C

Intervention: Pioglitazone (Drug); Increase response to interferon alpha plus ribavirin by increasing insulin sensitivity (Drug)

Phase: Phase 2

Status: Suspended

Sponsored by: University Hospital, Geneva

Official(s) and/or principal investigator(s):
Francesco Negro, Prof, Principal Investigator, Affiliation: University of Geneva, Switzerland

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.

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)

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

Primary outcome: Early virological response

Secondary outcome:

Undetectable serum HCV RNA after 4, 24 weeks and 48 weeks of therapy

Changes (vs. baseline) of body weight, HOMA score, after 4, 12 and 48 weeks of therapy and after 24 weeks of follow-up

Improvement (vs. baseline) of glucose tolerance parameters after 12 and 48 weeks of therapy and after 24 weeks of follow-up

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Service de Gastroentérologie et d'Hépatologie, University Hospital, Geneva, GE 1211, Switzerland

Related publications:

Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez E, Castillo J. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005 Mar;128(3):636-41.

Starting date: January 2007
Ending date: July 2007
Last updated: April 10, 2008