The Effects of Oral Hypoglycemic Agents on Chronic Hepatitis C Patients Receiving Peg-Intron Plus Ribavirin
Information source: National Taiwan University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis C
Intervention: Pioglitazone (Drug); Acarbose (Drug); Metformin (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: National Taiwan University Hospital Official(s) and/or principal investigator(s): Jia-Horng Kao, M.D., PhD., Principal Investigator, Affiliation: National Taiwan University Hospital
Summary
Pegylated interferon in combination with ribavirin is the current standard treatment of
chronic hepatitis C virus infection, but is expensive and has several adverse effects. To
modify this standard treatment by optimizing its therapeutic effect and decreasing its
adverse events are important. Recent studies have identified a close link between metabolic
profiles, insulin resistance and Hepatitis C Virus (HCV) infection. Several pilot studies in
western world have have found beneficial effects of oral hypoglycemic agents on chronic
Hepatitis C (CHC) genotype 1 infected patients. Whether this concept still holds true in
Taiwanese people remains unknown.
The objective of this clinical trial is to evaluate the effect of oral hypoglycemic agents
(daily for 4 weeks of run-in period and 8 weeks of combination treatment) on CHC genotype 1
infected Taiwanese patients receiving 48 weeks of Peg-IFN plus ribavirin (RBA), and the
enrolled subjects will be randomized into 4 treatment groups (including Acarbose, Metformin,
Pioglitazone and standard care control groups). During the trial and 24 weeks after the end
of treatment, serial serum HCV RNA, alanine aminotransferase (ALT) levels, and other
clinical data will be evaluated to determine the therapeutic response and adverse events of
the CHC patients.
Clinical Details
Official title: An Open-label, Multi-center, Randomized Study Comparing the Effects of Oral Hypoglycemic Agents on Viral Kinetics of Chronic Hepatitis C Patients Receiving Pegylated Interferon Alfa 2b Plus Ribavirin
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Sustained Virologic Response
Secondary outcome: serum ALT normalization, and histologic improvement
Detailed description:
Pegylated interferon in combination with ribavirin is the current standard treatment of
chronic hepatitis C virus infection, but is expensive and has several adverse effects. To
modify this standard treatment by optimizing its therapeutic effect and decreasing its
adverse events are important.
Recent studies have identified a close link between metabolic profiles, insulin resistance
and HCV infection. Chronic hepatitis C (CHC) patients with higher pretreatment HOMA-IR
(insulin resistance) index have poor therapeutic response than the ones with lower HOMA-IR
index. Thus, it is reasonable to increase the therapeutic response of CHC patients by
lowering insulin resistance. Several pilot studies in western world have been conducted to
evaluate this concept by adding oral hypoglycemic agents into pegylated interferon plus
ribavirin treatment, and have found beneficial effects of oral hypoglycemic agents on CHC
genotype 1 infected patients. Whether this concept still holds true in Taiwanese people
remains unknown.
To evaluate the effect of oral hypoglycemic agents on CHC genotype 1 infected Taiwanese
patients, we design this study and evaluate the virologic, biochemical and histological
responses of CHC patients receiving pegylated interferon plus ribavirin treatment, and hope
to identify similar beneficial effects of oral hypoglycemic agents in CHC Taiwanese
patients.
We plan to enroll about 80 chronic hepatitis C genotype 1 infected patients from the clinics
into this study. All patients should have informed consent, not receive any interferon-based
therapy or anti-viral medication, abstinence from alcohol beverage for more than 6 months
and conformed to the regulations of Bureau of National Health Insurance, Taiwan. All
patients will be randomly assigned into 4 different treatment arms. The patients assigned
into the first 3 arms will receive one kind of the following oral hypoglycemic agents, such
as Acarbose, Metformin, or Pioglitazone for 12 weeks (including 4 weeks of run-in period and
8 weeks of combination treatment with pegylated interferon alfa plus ribavirin). From week
13, all the patients of the first 3 arms will receive pegylated interferon alfa plus
ribavirin for 40 weeks. The last arm is the control group; all the patients in the last arm
will receive standard pegylated interferon alfa plus ribavirin treatment for 48 weeks.
During the trial and 24 weeks after the end of treatment, the serum HCV RNA levels, clinical
and biochemical data will be evaluated to determine the therapeutic response and adverse
events of the patients.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Treatment naïve
2. Age old than 18 years old
3. Anti-HCV positive > 6 months
4. Detectable serum quantitative HCV-RNA
5. HCV genotype 1
6. Serum alanine aminotransferase levels above the upper limit of normal with 6 months
of enrollment
7. Pre-treatment HOMA-IR ≧ 2. 0. (HOMA-IR = fasting insulin (mU/L) x fasting glucose
(mg/dL) x 0. 05551/22. 5)
Exclusion Criteria:
1. Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for
women)
2. Neutropenia (neutrophil count <1,500 per cubic milliliter)
3. Thrombocytopenia (platelet <90,000 per cubic milliliter)
4. Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
5. Chronic alcohol abuse (daily consumption > 20 gram per day in male and >10gram per
day in female).
6. Diabetes Mellitus history or under oral hypoglycemic agents therapy Liver cirrhosis
7. Serum creatinine level more than 1. 5 times the upper limit of normal Autoimmune liver
disease
8. Neoplastic disease
9. An organ transplant
10. Immunosuppressive therapy
11. Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases,
psychiatric diseases, neurological diseases, diabetes mellitus
12. Evidence of drug abuse
13. Unwilling to have contraception
Locations and Contacts
National Taiwan University Hospital Department of Internal Medicine,, Taipei 10002, Taiwan
Additional Information
Starting date: November 2009
Last updated: November 23, 2012
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