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The Effects of Oral Hypoglycemic Agents on Chronic Hepatitis C Patients Receiving Peg-Intron Plus Ribavirin

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2012 by National Taiwan University Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Schering-Plough
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01025765
First received: December 2, 2009
Last updated: November 23, 2012
Last verified: November 2012

December 2, 2009
November 23, 2012
November 2009
December 2012   (final data collection date for primary outcome measure)
Sustained Virologic Response [ Time Frame: at the end of 24 weeks post-treatment follow-up ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01025765 on ClinicalTrials.gov Archive Site
serum ALT normalization, and histologic improvement [ Time Frame: at the end of treatment and 24 weeks after the end of treatment ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
The Effects of Oral Hypoglycemic Agents on Chronic Hepatitis C Patients Receiving Peg-Intron Plus Ribavirin
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

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Hepatitis C
  • Drug: Pioglitazone
    Pioglitazone(30mg qd) for 4 weeks of run-in period and 8 weeks of combination treatment with Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg).
    Other Name: Pioglitazone
  • Drug: Acarbose
    Acarbose (50 mg/per meal) for 4 weeks of run-in period and 8 weeks of combination treatment with Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg).
    Other Name: Acarbose
  • Drug: Metformin
    Metformin (500 mg tid) 4 weeks of run-in period and 8 weeks of combination treatment with Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg). From week 13, all the subjects will receive pegylated interferon alfa plus ribavirin for 40 weeks.
    Other Name: Metformin
  • No Intervention: Standard care of CHC
    From week 5, all the patients will receive Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg) for 48 weeks.
  • Experimental: Pioglitazone
    From week 5, all the patients will receive Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg) for 48 weeks.
    Intervention: Drug: Pioglitazone
  • Experimental: Acarbose
    From week 5, all the patients will receive Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg) for 48 weeks.
    Intervention: Drug: Acarbose
  • Experimental: Metformin
    From week 5, all the patients will receive Peginterferon alfa-2b (1.5/μg per kg) per week plus Ribavirin 1000-1200 mg/day (≥ 75 kg, 1200 mg; < 75 kg, 1000mg) for 48 weeks.
    Intervention: Drug: Metformin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
80
December 2012
December 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
NCT01025765
200905056M
No
National Taiwan University Hospital
National Taiwan University Hospital
  • Schering-Plough
  • Merck Sharp & Dohme Corp.
Principal Investigator: Jia-Horng Kao, M.D., PhD. National Taiwan University Hospital
National Taiwan University Hospital
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP