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

This study has suspended participant recruitment.
(The tested combination was ineffective.)
Sponsor:
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT00433069
First received: February 8, 2007
Last updated: April 10, 2008
Last verified: April 2008
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Drug: Pioglitazone
Drug: Increase response to interferon alpha plus ribavirin by increasing insulin sensitivity
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Early virological response [ Time Frame: Week 12 of triple combined therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Undetectable serum HCV RNA after 4, 24 weeks and 48 weeks of therapy [ Time Frame: Week 2, 24 and 48 of therapy ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 35
Study Start Date: January 2007
Estimated Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433069

Locations
Switzerland
Service de Gastroentérologie et d'Hépatologie, University Hospital
Geneva, GE, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Francesco Negro, Prof University of Geneva, Switzerland
  More Information

Publications:
Responsible Party: Prof. Francesco Negro, University Hospital of Geneva
ClinicalTrials.gov Identifier: NCT00433069     History of Changes
Other Study ID Numbers: GE-DMI-05-116, The SASL 22 Study
Study First Received: February 8, 2007
Last Updated: April 10, 2008
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Geneva:
Chronic hepatitis C
Insulin resistance
Pioglitazone
Non-responders
Chronic hepatitis C that has previously failed to respond to a pegylated-interferon-alpha / ribavirin combination

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Insulin Resistance
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Interferon-alpha
Interferons
Ribavirin
Peginterferon alfa-2a
Insulin, Globin Zinc
Pioglitazone
Insulin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014