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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2006 by University of Turin, Italy.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT00370617
First received: August 30, 2006
Last updated: November 13, 2006
Last verified: November 2006
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Insulin Resistance
Drug: metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • 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:
  • 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

Estimated Enrollment: 200
Study Start Date: September 2006
Estimated Study Completion Date: January 2009
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00370617

Contacts
Contact: Mario Rizzetto, MD +39-011-6336397 mrizzetto@molinette.piemonte.it
Contact: Elisabetta Bugianesi, MD +39-011-6336397 ebugianesi@yahoo.it

Locations
Italy
Division of Gastroenterology, University of Torino, Ospedale San Giovanni Battista Recruiting
Torino, Italy, 10126
Contact: Mario Rizzetto, MD    +39-011-6336397    mrizzetto@molinette.piemonte.it   
Contact: Elisabetta Bugianesi, MD    +39-011-6336397    ebugianesi@yahoo.it   
Sub-Investigator: Elisabetta Bugianesi, MD         
Sponsors and Collaborators
University of Turin, Italy
Investigators
Principal Investigator: Mario Rizzetto, MD University of Torino
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00370617     History of Changes
Other Study ID Numbers: METVIRAL
Study First Received: August 30, 2006
Last Updated: November 13, 2006
Health Authority: Italy: Ministry of Health

Keywords provided by University of Turin, Italy:
chronic hepatitis C
insulin resistance
therapy

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
Insulin
Metformin
Interferons
Ribavirin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014