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

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 Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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:

MedlinePlus related topics: Diabetes Medicines Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Metformin Metformin hydrochloride Ribavirin Acarbose Pioglitazone Pioglitazone hydrochloride Peginterferon Alfa-2b

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]


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). Other Name: 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.	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
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. Other Name: Metformin

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


Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Treatment naïve
Age old than 18 years old
Anti-HCV positive > 6 months
Detectable serum quantitative HCV-RNA
HCV genotype 1
Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment
Pre-treatment HOMA-IR ≧ 2.0. (HOMA-IR = fasting insulin (mU/L) x fasting glucose (mg/dL) x 0.05551/22.5)

Exclusion Criteria:

Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
Neutropenia (neutrophil count <1,500 per cubic milliliter)
Thrombocytopenia (platelet <90,000 per cubic milliliter)
Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
Chronic alcohol abuse (daily consumption > 20 gram per day in male and >10gram per day in female).
Diabetes Mellitus history or under oral hypoglycemic agents therapy Liver cirrhosis
Serum creatinine level more than 1.5 times the upper limit of normal Autoimmune liver disease
Neoplastic disease
An organ transplant
Immunosuppressive therapy
Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
Evidence of drug abuse
Unwilling to have contraception

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided


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
Study First Received:	December 2, 2009
Last Updated:	November 23, 2012
Health Authority:	Taiwan: Department of Health

Additional relevant MeSH terms:


Hepatitis C Hepatitis C, Chronic Hepatitis, Chronic Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis, Viral, Human Liver Diseases RNA Virus Infections Virus Diseases Acarbose Hypoglycemic Agents Interferon-alpha	Metformin Peginterferon alfa-2b Pioglitazone Ribavirin Anti-Infective Agents Antimetabolites Antiviral Agents Enzyme Inhibitors Immunologic Factors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015