Study the Relationship Between Obesity and Hepatitis C Replication

Study Overview
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Brief Summary
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Patients with chronic hepatitis C viral infection (HCV) and with a BMI greater than 25Kg/m2 are refractory to medical treatment. Also, HCV replication seems to be affected when modeling insulin resistance in replicon cell culture systems. PPARg -agonist (Pioglitazone) is effective in controlling liver inflammation in obese subjects with non-alcoholic steatohepatitis (NASH) and also improving insulin sensitivity. Therefore, we hypothesize that improving insulin resistance and /or inflammation may affect HCV replication and viral kinetics. Independently of PPARg pathways, Prednisone may increase HCV viral kinetics. .

Detailed Description
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This is a randomized, two arm clinical trial. The investigators performing the primary and secondary endpoints are blinded to subject identifiers and arm identifiers. Subject's screening for HCV Genotype 4 started in Agouza Hospital in July 2010 and ended in February, 2011. No recruitment has occurred for HCV Genotype 1.

Official Title
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A Randomized, Partially Blinded, Pilot Study of the Effects of Pioglitazone on HCV RNA in Overweight Subjects With Chronic HCV Genotypes 1 or 4 Infection.

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infection with HCV genotype 1 or 4 (subjects infected with multiple genotypes are not eligible) BMI greater than 25 Kg/m2 HCV-infected subjects naïve to treatment: subjects who either have never been treated for HCV infection or who previously received HCV treatment ending more than 3 months prior to enrollment for not longer than 2 weeks Plasma HCV RNA concentration of >10,000 IU/mL at the screening evaluation Exclusion Criteria: Previous intolerance to Pioglitazone, Rosiglitazone, Troglitazone or corticosteroids Women who are pregnant or breastfeeding History of diabetes mellitus requiring treatment other than diet Decompensated liver disease or other known causes of liver disease including, but not limited to autoimmune hepatitis, Wilson's disease, hemochromatosis, primary biliary cirrhosis, schistosomiasis, sclerosing cholangitis, alcohol- or drug-induced liver disease, or alpha-one antitrypsin deficiency Concurrent hepatitis B virus (HBV) infection Known immunodeficiency disease, autoimmune disorders or active gastrointestinal disease Abuse of alcohol or illicit drugs within 6 months before enrollment Use of an investigational drug within 4 weeks before the screening visit or during the screening period. Use of systemic immunosuppressants History of poorly controlled psychiatric disease or poorly controlled pulmonary disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br> | Drug: Pioglitazone<br>* Pioglitazone will be taken at a dose of 30 mg for up to 14 days<br>* Other names: ACTOS;|
| Experimental: Prednisone<br> | Drug: Prednisone<br>* Prednisone will be taken at a dose of 40 mg for up to 4 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA | Only in the Pioglitazone group | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA | Only in the Prednisone group | Day 4 | 
| Serum indicators of insulin resistance (fasting glucose, insulin, lipids and serum retinol binding protein-4); adiponectins and inflammatory cytokines. |  | Day 14 (Pioglitazone) and Day 4 (Prednisone) | 
| ALT and AST |  | Day 14 (Pioglitazone) and Day 4 (Prednisone) |