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

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ClinicalTrials.gov Identifier: NCT00370617
Recruitment Status : Unknown
Verified November 2006 by University of Turin, Italy.
Recruitment status was:  Recruiting
First Posted : August 31, 2006
Last Update Posted : November 14, 2006
Sponsor:
Information provided by:
University of Turin, Italy

Tracking Information
First Submitted Date  ICMJE August 30, 2006
First Posted Date  ICMJE August 31, 2006
Last Update Posted Date November 14, 2006
Study Start Date  ICMJE September 2006
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2006)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2006)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pegylated-Interferon and Ribavirin Plus Metformin in the Treatment of Chronic HCV Infection and Insulin Resistance
Official Title  ICMJE 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
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Hepatitis C
  • Insulin Resistance
Intervention  ICMJE Drug: metformin
Study Arms  ICMJE Not Provided
Publications * Romero-Gómez M, Del Mar Viloria M, Andrade RJ, Salmerón J, Diago M, Fernández-Rodríguez CM, Corpas R, Cruz M, Grande L, Vázquez L, Muñoz-De-Rueda P, López-Serrano P, Gila A, Gutiérrez ML, Pérez C, Ruiz-Extremera A, Suárez 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Enrollment  ICMJE
 (submitted: August 30, 2006)
200
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE January 2009
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00370617
Other Study ID Numbers  ICMJE METVIRAL
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE University of Turin, Italy
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mario Rizzetto, MD University of Torino
PRS Account University of Turin, Italy
Verification Date November 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP