Study the Relationship Between Obesity and Hepatitis C Replication

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.

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. .

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Pioglitazone; Drug: Prednisone

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Giza, Egypt
    • Agouza Hospital
• United States
  • California
    • San Diego, California, United States, 92037
      • University of California at San Diego Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone	Drug: Prednisone; Prednisone will be taken at a dose of 40 mg for up to 4 days
Experimental: Pioglitazone	Drug: Pioglitazone; Pioglitazone will be taken at a dose of 30 mg for up to 14 days; Other Names: ACTOS

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Mario Chojkier, MD, UCSD; Principal Investigator: Martina Buck, PhD, UCSD; Principal Investigator: Hesham Elkhayat, MD, cairo university, Egypt

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2008
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: July 6, 2010
• First Posted (Estimate): July 8, 2010

Study Record Updates

• Last Update Posted (Actual): December 2, 2019
• Last Update Submitted That Met QC Criteria: November 27, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Pioglitazone
• Other Study ID Numbers: 060913