Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00188240
Status:
UNKNOWN
Last Update Posted:
2005-11-29
First Post:
2005-09-09
Brief Title:
Insulin Resistance Associated With Chronic Hepatitis C CHC and the Effect of Antiviral Therapy
Sponsor:
University Health Network Toronto
Organization:
University Health Network Toronto
Study Overview
Official Title:
Insulin Resistance Associated With Chronic Hepatitis C CHC and the Effect of Anti-Viral Therapy
Status:
UNKNOWN
Status Verified Date:
2005-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
The first phase will include patients with hepatitis C who are candidates for anti-viral treatment and patients with chronic hepatitis B who have undergone a recent liver biopsy showing hepatitis without cirrhosis with equal numbers in each group 100 group
Phase 2 40 patients- Patients with hepatitis C found in phase 1 by the HOMA test to have increased insulin resistance will be recruited to phase 2 interventional phase Patients with HBV infection will not be studied further
The study will be conducted at a single center using an open-label design All patients will be treatment naïve Up to 40 patients will be treated per current standard of care with combination pegylated interferon alfa and ribavirin Phase 2 Patients with genotype 2 or 3 will be treated with combination weekly Pegasys with a daily Copegus dose of 800 mg given for 24 weeks Group A Patients with genotype non-2 or 3 will be treated with combination weekly Pegasys with a daily Copegus dose of 1000-1200 mg given for 48 weeks Group B Both groups will have an untreated follow-up period of 24 weeks Pegasys will be administered sc once weekly 180 microg in 05 or 1 mL solution and Copegus will be taken po daily in split doses of 400 mg in the morning and 400 mg in the evening ie 2 tablets of 200 mg bid For doses of 1000 mg genotype non- 2 or 3 patients whose body weight 75 kg Copegus will be administered po daily 400 mg ie 2 tablets of 200 mg in the morning and 600 mg ie 3 tablets of 200 mg in the evening For genotype non-2 or 3 patients whose body weight is 75 kg 600 mg ie 3 tablets of 200 mg in the morning and 600 mg ie 3 tablets of 200 mg in the evening is recommended All patients in this study will receive Copegus treatment with food By definition Copegus with food means taking their doses within 1 hour before or 2 hours after a meal The meal should be considered regular as opposed to fat-restricted
All 40 patients who meet inclusion criteria will also have indices of body fat assessed through calculation of their BMI DEXA scanning and waist-to-hip circumference measurements Prior to therapy all patients will undergo the OGTT which is a dynamic test for insulin resistance providing accurate information on the relationship between insulin and glucose
At week 12 of treatment patients will have a quantitative assessment of HCV viral load and a second OGTT The current standard of therapy is to discontinue anti-viral therapy in patients with genotype 1 or 4 without a 2-log fall in HCV RNA Those who have a 2-log fall in HCV RNA are expected to have a SVR Patients to be continued on anti-viral therapy will then be followed to SVR
Twenty-four weeks after completion of anti-viral therapy a OGTT will be repeated SVR OGTT The effect of viral clearance on insulin resistance will be assessed by comparing the OGTT at SVR SVR OGTT to pre-treatment OGTT
Patients who are Non-Responders should also be assessed for safety 4-8 weeks after their last dose of test medication following premature discontinuation from the study Non-Responders are defined as patients without a 2-log drop in PCR between baseline and week 12 or a positive PCR at their last visit Responders should be followed for until Week 48 Group A patients or Week 72 Group B patients Responders are defined as patients who have a 2-log drop in PCR between baseline and week 12 and a negative PCR at their last visit Female patients receiving Copegus should continue to do the home-based pregnancy test every 4 weeks for the 6-month period after the last dose of study drug
Efficacy assessments consist of serum HCV-RNA via PCR Quantitative viral titers AMPLICOR HCV MONITOR Test v20 will be obtained at Weeks 0 and 12 from all patients Qualitative HCV-RNA results AMPLICORÒ HCV Test v20 will be obtained at treatment period Week 24 for all patients and Week 48 for group B in addition during follow-up at week 24 for all patients
Insulin resistance as determined by the OGTT method will be assessed prior to initiation of therapy at 12 weeks of therapy and during follow-up at week 24 for all patients
Study Outcome
Phase 1 - 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 2 - 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
Phase 2 40 patients- Patients with hepatitis C found in phase 1 by the HOMA test to have increased insulin resistance will be recruited to phase 2 interventional phase Patients with HBV infection will not be studied further
The study will be conducted at a single center using an open-label design All patients will be treatment naïve Up to 40 patients will be treated per current standard of care with combination pegylated interferon alfa and ribavirin Phase 2 Patients with genotype 2 or 3 will be treated with combination weekly Pegasys with a daily Copegus dose of 800 mg given for 24 weeks Group A Patients with genotype non-2 or 3 will be treated with combination weekly Pegasys with a daily Copegus dose of 1000-1200 mg given for 48 weeks Group B Both groups will have an untreated follow-up period of 24 weeks Pegasys will be administered sc once weekly 180 microg in 05 or 1 mL solution and Copegus will be taken po daily in split doses of 400 mg in the morning and 400 mg in the evening ie 2 tablets of 200 mg bid For doses of 1000 mg genotype non- 2 or 3 patients whose body weight 75 kg Copegus will be administered po daily 400 mg ie 2 tablets of 200 mg in the morning and 600 mg ie 3 tablets of 200 mg in the evening For genotype non-2 or 3 patients whose body weight is 75 kg 600 mg ie 3 tablets of 200 mg in the morning and 600 mg ie 3 tablets of 200 mg in the evening is recommended All patients in this study will receive Copegus treatment with food By definition Copegus with food means taking their doses within 1 hour before or 2 hours after a meal The meal should be considered regular as opposed to fat-restricted
All 40 patients who meet inclusion criteria will also have indices of body fat assessed through calculation of their BMI DEXA scanning and waist-to-hip circumference measurements Prior to therapy all patients will undergo the OGTT which is a dynamic test for insulin resistance providing accurate information on the relationship between insulin and glucose
At week 12 of treatment patients will have a quantitative assessment of HCV viral load and a second OGTT The current standard of therapy is to discontinue anti-viral therapy in patients with genotype 1 or 4 without a 2-log fall in HCV RNA Those who have a 2-log fall in HCV RNA are expected to have a SVR Patients to be continued on anti-viral therapy will then be followed to SVR
Twenty-four weeks after completion of anti-viral therapy a OGTT will be repeated SVR OGTT The effect of viral clearance on insulin resistance will be assessed by comparing the OGTT at SVR SVR OGTT to pre-treatment OGTT
Patients who are Non-Responders should also be assessed for safety 4-8 weeks after their last dose of test medication following premature discontinuation from the study Non-Responders are defined as patients without a 2-log drop in PCR between baseline and week 12 or a positive PCR at their last visit Responders should be followed for until Week 48 Group A patients or Week 72 Group B patients Responders are defined as patients who have a 2-log drop in PCR between baseline and week 12 and a negative PCR at their last visit Female patients receiving Copegus should continue to do the home-based pregnancy test every 4 weeks for the 6-month period after the last dose of study drug
Efficacy assessments consist of serum HCV-RNA via PCR Quantitative viral titers AMPLICOR HCV MONITOR Test v20 will be obtained at Weeks 0 and 12 from all patients Qualitative HCV-RNA results AMPLICORÒ HCV Test v20 will be obtained at treatment period Week 24 for all patients and Week 48 for group B in addition during follow-up at week 24 for all patients
Insulin resistance as determined by the OGTT method will be assessed prior to initiation of therapy at 12 weeks of therapy and during follow-up at week 24 for all patients
Study Outcome
Phase 1 - 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 2 - 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None