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

Overview[ - collapse ][ - ]

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.
ConditionChronic Hepatitis C
Insulin Resistance
InterventionDrug: metformin
PhasePhase 4
SponsorUniversity of Turin, Italy
Responsible PartyUniversity of Turin, Italy
ClinicalTrials.gov IdentifierNCT00370617
First ReceivedAugust 30, 2006
Last UpdatedNovember 13, 2006
Last verifiedNovember 2006

Tracking Information[ + expand ][ + ]

First Received DateAugust 30, 2006
Last Updated DateNovember 13, 2006
Start DateSeptember 2006
Estimated Primary Completion DateJanuary 2009
Current 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
Current 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

Descriptive Information[ + expand ][ + ]

Brief TitlePegylated-Interferon and Ribavirin Plus Metformin in the Treatment of Chronic HCV Infection and Insulin Resistance
Official TitleAn 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 TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Chronic Hepatitis C
  • Insulin Resistance
InterventionDrug: metformin
Study Arm (s)Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment200
Estimated Completion DateJanuary 2009
Estimated Primary Completion DateNot Provided
Eligibility 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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Mario Rizzetto, MD
+39-011-6336397
mrizzetto@molinette.piemonte.it
Location CountriesItaly

Administrative Information[ + expand ][ + ]

NCT Number NCT00370617
Other Study ID NumbersMETVIRAL
Has Data Monitoring CommitteeNot Provided
Information Provided ByUniversity of Turin, Italy
Study SponsorUniversity of Turin, Italy
CollaboratorsNot Provided
Investigators Principal Investigator: Mario Rizzetto, MD University of Torino
Verification DateNovember 2006

Locations[ + expand ][ + ]

Division of Gastroenterology, University of Torino, Ospedale San Giovanni Battista
Torino, Italy, 10126
Contact: Mario Rizzetto, MD | +39-011-6336397 | mrizzetto@molinette.piemonte.it
Sub-Investigator: Elisabetta Bugianesi, MD
Recruiting