Pioglitazone in Hepatitis C

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2005 by University of Michigan.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00189163
First received: September 13, 2005
Last updated: February 15, 2006
Last verified: September 2005
  Purpose

Insulin resistance (IR), a key factor in the development of steatosis, is a common finding in patients with hepatitis C virus (HCV) infection. In patients with genotype 1 infection, IR has been noted in up to 80% of patients in some studies. In patients with non-alcoholic fatty liver disease (NAFLD) who have evidence of nonalcoholic steatohepatitis (NASH), the role of IR leading to decreased fatty acid oxidation, increased production of pro-inflammatory cytokines and increased oxidative stress had been proposed as an important mechanism leading to steatosis and subsequent liver cell injury. Recently, an association between steatosis and hepatic fibrosis has been emphasized in HCV infection, similar to that described in patients with NAFLD. While IR and hepatic steatosis are common findings in patients with HCV infection, the latter with prevalence rates of 40% to 70%, and different HCV genotypes confers distinct risks for steatosis; a greater degree of steatosis is seen in patients with genotype 3 infection compared to others. Similar to that seen in patients with NAFLD, patients infected with genotype 1 HCV show a relationship between body mass index (BMI) and risk for steatosis. However, in up to 30% of patients with HCV infection and hepatic steatosis, no other risk factors for steatosis can be identified. The investigators' preliminary data will show that even in HCV infected individuals with low BMI and no steatosis, there is IR and the risk for steatosis is increased when directly compared to NAFLD patients. Recent data also suggest that the presence of hepatic steatosis is an independent predictor of decreased response to antiviral therapy even when controlling for genotype. This is especially important in patients with type 1 infection.

The investigators hypothesize that in patients with HCV genotype 1 infection, treatment with antiviral therapy will have a partial effect on reducing insulin resistance (IR) and steatosis and this is augmented by the addition of an insulin sensitizing thiazolidinedione (TZD) agent such as pioglitazone to the treatment regimen. The investigators also hypothesize that the rate of sustained virological response (SVR) will be higher in the antiviral regimen + pioglitazone treated group compared to patients receiving antiviral therapy alone.

The investigators' specific aims are the following:

  1. To assess the improvement in insulin sensitivity in patients with treatment naïve genotype 1 chronic hepatitis C treated with standard antiviral therapy + pioglitazone or placebo
  2. To assess the improvement in hepatic steatosis in patients with treatment naïve genotype 1 chronic hepatitis C after treatment with standard antiviral therapy + pioglitazone or placebo
  3. To assess the rates of sustained virological response (SVR) among patients with treatment naïve genotype 1 chronic hepatitis C treated with standard antiviral therapy + pioglitazone compared to standard antiviral therapy + placebo

Condition Intervention Phase
Chronic Hepatitis C
Drug: Pioglitazone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Pioglitazone in Hepatitis C: A Randomized, Double Blind, Placebo-Controlled Study

Resource links provided by NLM:


Further study details as provided by University of Michigan:

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All eligible adult patients with compensated liver disease due to chronic infection with HCV and genotype 1 infection who are treatment naïve will be enrolled into the study.
  • All racial and ethnic groups will be recruited into this study.
  • Males and females: age > 18 years
  • Chronic hepatitis C: history of serum positive for HCV antibody (anti-HCV) and HCV RNA. Patients should have evidence of chronic hepatitis with a minimum fibrosis score of 1 on liver biopsy done within 6 months of enrollment.
  • Insulin resistance based on HOMA index value (HOMA-IR) of > 2.0 during screening. HOMA-IR is a well recognized and validated index of insulin resistance in both non-diabetic and diabetic populations and has been shown to have a good correlation with ‘clamp’ techniques that are intensive. HOMA is also used routinely to assess longitudinal changes including assessment of the effects of treatment. In general, a HOMA-IR value of > 1.5 is considered abnormal based on repeat testing measurements performed by both HOMA assessment and by euglycemic clamp technique and is considered representative of decreased insulin sensitivity. Although insulin secretion is pulsatile, the correlation between HOMA computed from repeat sampling (using a mean of three samples taken at 5-minute intervals to compute HOMA) and the value obtained from a single basal sample to determine insulin sensitivity has been shown to be near perfect even in patients with type 2 diabetes (r = 0.99, p < 0.0001). The investigators will use a HOMA-IR value of > 2.0 as part of the inclusion criteria in this study.
  • Able and willing to provide written informed consent

Exclusion Criteria:

  • Hepatitis C patients who underwent previous therapy for their liver disease
  • Genotype other than type 1
  • Histological evidence of cirrhosis or confirmed hepatocellular carcinoma (HCC)
  • Patients with cirrhosis and decompensated liver disease and any patient, in whom a liver biopsy is contraindicated, will be excluded.
  • Evidence of other causes of chronic liver disease
  • Diabetes mellitus
  • New York Heart Association (NYHA) functional classification for cardiac disease: class III and IV patients
  • Human immunodeficiency virus (HIV) antibody positive
  • Patients with solid organ transplants
  • Pregnancy or breast feeding
  • Participation in any other clinical trial within 90 days of entry into this trial.
  • Unwilling to consent to the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00189163

Contacts
Contact: Hari S Conjeevaram, M.D. 734-615-9759 omsairam@umich.edu

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Hari S Conjeevaram, M.D.    734-615-9759    omsairam@umich.edu   
Principal Investigator: Hari S Conjeevaram, M.D.         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Hari S Conjeevaram, M.D. University of Michigan
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00189163     History of Changes
Other Study ID Numbers: pio-hcv-108, IRB Protocol Number: 2004-0883, GCRC Protocol Number: 2085
Study First Received: September 13, 2005
Last Updated: February 15, 2006
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
Hepatitis C
Genotype 1
Insulin Resistance
Pioglitazone

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014