Clinical trial NCT01157975: Study the Relationship Between Obesity and Hepatitis C Replication
Official title: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hepatitis C
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2010-07-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: HCV RNA
timeFrame: 2 weeks
Secondary outcomes:
measure: HCV RNA
timeFrame: Day 4
measure: Serum indicators of insulin resistance (fasting glucose, insulin, lipids and serum retinol binding protein-4); adiponectins and inflammatory cytokines.
timeFrame: Day 14 (Pioglitazone) and Day 4 (Prednisone)
measure: ALT and AST
timeFrame: Day 14 (Pioglitazone) and Day 4 (Prednisone)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego Hospitals
state: California
city: Giza
country: Egypt
facility: Agouza Hospital
Study officials:
affiliation: UCSD
name: Mario Chojkier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCSD
name: Martina Buck, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cairo University, Egypt
name: Hesham Elkhayat, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chojkier M, Elkhayat H, Sabry D, Donohue M, Buck M. Pioglitazone decreases hepatitis C viral load in overweight, treatment naive, genotype 4 infected-patients: a pilot study. PLoS One. 2012;7(3):e31516. doi: 10.1371/journal.pone.0031516. Epub 2012 Mar 7.