Hepatitis C
Conditions
Brief summary
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
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.
Interventions
DRUGPioglitazone
Pioglitazone will be taken at a dose of 30 mg for up to 14 days
DRUGPrednisone
Prednisone will be taken at a dose of 40 mg for up to 4 days
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HCV RNA | 2 weeks | Only in the Pioglitazone group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HCV RNA | Day 4 | Only in the Prednisone group |
| 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) | — |
Countries
Egypt, United States
Outcome results
None listed