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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.

Verified November 2006 by University of Turin, Italy.
Recruitment status was: Recruiting

Sponsor:

ClinicalTrials.gov Identifier:

NCT00370617

First Posted: August 31, 2006

Last Update Posted: November 14, 2006

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Information provided by:

University of Turin, Italy

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 Intervention Model: Parallel Assignment Masking: None (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:

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Metformin Metformin hydrochloride Insulin

U.S. FDA Resources

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:

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

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:

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.


ClinicalTrials.gov Identifier:	NCT00370617 History of Changes
Other Study ID Numbers:	METVIRAL
First Submitted:	August 30, 2006
First Posted:	August 31, 2006
Last Update Posted:	November 14, 2006
Last Verified:	November 2006

Keywords provided by University of Turin, Italy:


chronic hepatitis C insulin resistance therapy

Additional relevant MeSH terms:


Hepatitis Hepatitis C Hepatitis, Chronic Insulin Resistance Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Hyperinsulinism Glucose Metabolism Disorders	Metabolic Diseases Insulin Metformin Interferons Ribavirin Hypoglycemic Agents Physiological Effects of Drugs Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action

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