Insulin Resistance Associated With Chronic Hepatitis C (CHC) and the Effect of Antiviral Therapy

NCT00188240 | Unknown

• 1 other identifier: 03-0510-AE 04-0292-A
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The literature suggests that there may be an association between hepatitis C and type 2 diabetes mellitus independent of the presence of cirrhosis, the likely mechanism for which is insulin resistance. The prevalence of insulin resistance in patients with hepatitis C is unknown. Furthermore, there are no studies that indicate an increased prevalence of insulin resistance in patients with hepatitis C compared to other etiologies of liver disease. The role that hepatitis C may have in the development of insulin resistance is unclear. The effect of antiviral therapy for hepatitis C virus on insulin resistance has not been addressed. The long-term consequence of insulin resistance is type 2 diabetes mellitus. There is significant morbidity and mortality from type 2 diabetes mellitus in the general population, and similar complications would be expected in patients with hepatitis C and insulin resistance particularly if they develop type 2 diabetes mellitus. Our hypothesis: The prevalence of insulin resistance is increased in patients with chronic hepatitis C compared to chronic hepatitis B. Secondarily, insulin resistance when present in patients with chronic hepatitis C improves with successful antiviral therapy. This study has two phases. The first phase of our study will be to estimate the prevalence of insulin resistance in individuals with chronic hepatitis C without cirrhosis compared to patients with chronic hepatitis B without cirrhosis. The second phase of the study will be restricted to those patients with hepatitis C found to be insulin resistant from phase 1, in the absence of known risk factors for insulin resistance (cirrhosis, diabetes). The effect on insulin resistance of anti-viral therapy to eradicate hepatitis C will be assessed.

Conditions

Hepatitis C; Hepatitis B

Keywords

hepatitis C; insulin resistance; antiviral therapy

Outcome Measures

Primary Outcomes (3)

• Phase I - To evaluate the prevalence of insulin resistance in patients with hepatitis C without cirrhosis and compare it to that observed in patients with hepatitis B also without cirrhosis.

• Phase II - Interventional phase - To evaluate the effect of anti-viral therapy on insulin resistance, determined by the OGTT method, in patients with hepatitis C found to have insulin resistance pre-treatment.

• - To evaluate the safety, efficacy and tolerability of Pegasys (peginterferon alfa-2a) given in combination with Copegus (ribavirin) given for 24 weeks or 48 weeks in treatment naïve patients with chronic hepatitis C (CHC).

Interventions

Pegasys; Copegus. DRUG

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients attending Liver Clinic at Toronto Western Hospital, Toronto, ON, Canada
• Male and female patients
• Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
• Detectable serum HCV-RNA
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
• All fertile males and females receiving Copegus must be using two forms of effective contraception during treatment and during the 6 months after treatment end
• All patients should have insulin resistance (\>2.1) determined by the homeostasis model assessment (HOMA) method.

You may not qualify if:

• Women with ongoing pregnancy or breast feeding
• Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) \< 6 months prior to the first dose of study drug
• Any investigational drug \< 6 weeks prior to the first dose of study drug
• Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV)
• History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
• Signs or symptoms of hepatocellular carcinoma
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• Neutrophil count \<1500 cells/mm3 or platelet count \<90,000 cells/mm3 at screening
• Serum creatinine level \>1.5 times the upper limit of normal at screening
• History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
• History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
• Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
• Evidence of drug abuse (including excessive alcohol consumption) within one year of study entry

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Liver Clinic, Toronto Western Hospital, UHN.

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

MeSH Terms

Conditions

Hepatitis C; Hepatitis B; Insulin Resistance

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Hepadnaviridae Infections; DNA Virus Infections; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• E.J.L (Jenny) Heathcote, MD

  UHN - Toronto Western Hospital, University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tharini Ganeshram

CONTACT

416-603-5839

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2003
• Last Updated: November 29, 2005

Record last verified: 2005-09

Locations

CA (1)