Chronic Hepatitis CPhase 4NCT00370617
Pegylated-Interferon and Ribavirin Plus Metformin in the Treatment of Chronic HCV Infection and Insulin Resistance
A Phase 4 study testing metformin in people with Chronic Hepatitis C and Insulin Resistance, run by University of Turin, Italy at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis C, Insulin Resistance
- What is being tested?
- metformin
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2006to Jan 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Thyroid disease poorly controlled
- Overt cirrhosis, hepatocellular carcinoma
- Significant cardiac, renal, pulmonary disease, seizures.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Division of Gastroenterology, University of Torino, Ospedale San Giovanni Battista
Torino, 10126
Mario Rizzetto, MD, +39-011-6336397, mrizzetto@molinette.piemonte.it
Elisabetta Bugianesi, MD, +39-011-6336397, ebugianesi@yahoo.it
About this study
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
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.
Read the 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.
- Conditions
- Chronic Hepatitis C, Insulin Resistance
- Being tested
- metformin
- Keywords
- chronic hepatitis C, insulin resistance, therapy
- Medical subject headings
- Hepatitis C, Chronic, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metforminDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (4)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2006 (estimated)
- Study startSep 2006
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Investigators
- Mario Rizzetto, MD, Principal investigator, University of Torino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00370617
- Sponsor's protocol ID
- METVIRAL
- Status last verified
- Nov 2006
- First submitted
- 30 Aug 2006
- Last updated
- 14 Nov 2006
- Results posted
- No
Publications
Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez 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. doi: 10.1053/j.gastro.2004.12.049.
PubMed 15765399
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00370617
- Acronym / sponsor ID
- METVIRAL
- Conditions
- Chronic Hepatitis C, Insulin Resistance
- Keywords
- chronic hepatitis C, insulin resistance, therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- Sep 2006
- Study completion
- Jan 2009
- First posted
- 31 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metformin | Drug | – |
Primary outcome
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
4 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2006.
- Background: PubMed 15765399Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, Corpas R, Cruz M, Grande L, Vazquez L, Munoz-De-Rueda P, Lopez-Serrano P, Gila A, Gutierrez ML, Perez C, Ruiz-Extremera A, Suarez 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. doi: 10.1053/j.gastro.2004.12.049.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Rizzetto, MD principal investigator
University of Torino
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing metformin in people with Chronic Hepatitis C and Insulin Resistance, run by University of Turin, Italy at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Nov 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mario Rizzetto, MD (+39-011-6336397, mrizzetto@molinette.piemonte.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined end-point of non-detectable serum HCV-RNA (<100 copies/mL) and. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00370617, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2006.