Pegylated-Interferon and Ribavirin Plus Metformin in the Treatment of Chronic HCV Infection and Insulin Resistance

November 13, 2006 updated by: University of Turin, Italy

An Efficacy and Safety Study Comparing Pegylated-Interferon and Ribavirin Plus Metformin to Pegylated-Interferon and Ribavirin in the Treatment of naïve Patients With Genotype 1 Chronic HCV Infection and Insulin Resistance

Chronic hepatitis C virus (HCV) infection is associated with an increased risk for the development of type 2 diabetes and HCV infection itself may promote insulin resistance, irrespective of the severity of liver disease.

Insulin resistance seems to be genotype specific and may play a role in fibrogenesis in chronic hepatitis C.

In an "in vitro" model, increased levels of insulin may promote increased HCV replication.

RATIONALE Decreased insulin resistance and reduced hyperinsulinemia may facilitate the efficacy of anti-viral drugs on HCV replication.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis C virus (HCV) infection is associated with an increased risk for the development of type 2 diabetes and HCV infection itself may promote insulin resistance, irrespective of the severity of liver disease.

  • In patients with HCV infection, an increase in fasting insulin levels is associated with the presence of serum HCV core, the severity of hepatic fibrosis and a decrease in expression of insulin receptor substrate (IRS) 1 and IRS2, central molecules of the insulin-signaling cascade. Down-regulation of IRS1 and IRS2 has also been observed in HCV core-transgenic mice livers and HCV core-transfected human hepatoma cells.
  • High levels of tumor necrosis factor-alpha, which acts by disturbing tyrosine phosphorylation of insulin receptor substrate-1, may be associated with insulin resistance both in animal models and in HCV patients.

Insulin resistance seems to be genotype specific and may play a role in fibrogenesis in chronic hepatitis C.

  • In patients infected with genotype non-3, insulin resistance is associated with the degree of fibrosis, the rate of fibrosis progression and previous failed antiviral treatment.
  • Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin. A sustained virological response is achieved in 33% of patients with genotype 1 and insulin resistance compared with 60% of genotype 1 patients without insulin resistance.
  • Insulin resistance is associated with a 3-fold risk of failure to antiviral treatment in patients with genotype 1 In an "in vitro" model, increased levels of insulin may promote increased HCV replication.

RATIONALE Decreased insulin resistance and reduced hyperinsulinemia may facilitate the efficacy of anti-viral drugs on HCV replication.

INDICATION Genotype 1 Chronic HCV hepatitis (CHC) associated with insulin resistance (IR).

OBJECTIVES To compare the efficacy and safety of Pegylated-Interferon and Ribavirin plus metformin to Pegylated-Interferon and Ribavirin for treatment of naïve patients with Genotype 1 Chronic HCV infection and insulin resistance.

Study Type

Interventional

Enrollment

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Torino, Italy, 10126
        • Recruiting
        • Division of Gastroenterology, University of Torino, Ospedale San Giovanni Battista
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Elisabetta Bugianesi, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. No previous antiviral treatment
  2. Persistently elevated alanine aminotransferase (ALT) and quantifiable HCV-RNA (>2000 copies/ml)
  3. Liver biopsy (within 12 months) consistent with CHC with or without cirrhosis
  4. Compensated liver disease (Child-Pugh grade A)
  5. Insulin resistance (evaluated by HOMA-R and OGTT)
  6. Negative pregnancy test

Exclusion Criteria:

  1. Type 2 Diabetes (according to ADA criteria)
  2. BMI > 30
  3. Alcohol consumption > 30 g/day
  4. Other forms of liver disease (HBV, autoimmune, genetic), HIV infection.
  5. Anemia
  6. Psychiatric disease
  7. Thyroid disease poorly controlled
  8. Overt cirrhosis, hepatocellular carcinoma
  9. Significant cardiac, renal, pulmonary disease, seizures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Combined end-point of non-detectable serum HCV-RNA (<100 copies/mL) and
normal serum ALT activity at the end of the 24 week treatment-free follow up period

Secondary Outcome Measures

Outcome Measure
End-of-treatment virological and biochemical response
Sustained virological and biochemical response
End-of-treatment improvement of insulin resistance
End-of-treatment improvement of liver histology

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Turin, Italy

Investigators

  • Principal Investigator: Mario Rizzetto, MD, University of Torino

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Study Completion

January 1, 2009

Study Registration Dates

First Submitted

August 30, 2006

First Submitted That Met QC Criteria

August 30, 2006

First Posted (Estimate)

August 31, 2006

Study Record Updates

Last Update Posted (Estimate)

November 14, 2006

Last Update Submitted That Met QC Criteria

November 13, 2006

Last Verified

November 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • METVIRAL

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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