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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. The completion date has passed and the status has not been verified in more than two years.
Verified November 2012 by National Taiwan University Hospital.
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01025765
First Posted: December 4, 2009
Last Update Posted: November 27, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Schering-Plough
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
National Taiwan University Hospital
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C Drug: Pioglitazone Drug: Acarbose Drug: Metformin Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Sustained Virologic Response [ Time Frame: at the end of 24 weeks post-treatment follow-up ]

Secondary Outcome Measures:
  • serum ALT normalization, and histologic improvement [ Time Frame: at the end of treatment and 24 weeks after the end of treatment ]
Estimated Enrollment: 80
Study Start Date: November 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
 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).
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.
 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).
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.
 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.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01025765


Locations
Taiwan
National Taiwan University Hospital Department of Internal Medicine,
Taipei, Taiwan, 10002
Sponsors and Collaborators
National Taiwan University Hospital
Schering-Plough
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Jia-Horng Kao, M.D., PhD. National Taiwan University Hospital
  More Information

Responsible Party: National Taiwan University Hospital, Jia-Horng Kao, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01025765     History of Changes
Other Study ID Numbers: 200905056M
First Submitted: December 2, 2009
First Posted: December 4, 2009
Last Update Posted: November 27, 2012
Last Verified: November 2012

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pioglitazone
 Metformin
Hypoglycemic Agents
Acarbose
Ribavirin
Interferon-alpha
Peginterferon alfa-2b
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Glycoside Hydrolase Inhibitors
Enzyme Inhibitors