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.
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Locations
- 2
- Primary Endpoint
- HCV RNA
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Pioglitazone
Intervention: Pioglitazone (Drug)
Prednisone
Intervention: Prednisone (Drug)
Outcomes
Primary Outcomes
HCV RNA
Time Frame: 2 weeks
Only in the Pioglitazone group
Secondary Outcomes
- HCV RNA(Day 4)
- ALT and AST(Day 14 (Pioglitazone) and Day 4 (Prednisone))
- 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))
Investigators
Mario Chojkier
Professor of Medicine
University of California, San Diego