Assessing the Efficacy and Safety of Rosiglitazone Added to Standard Therapy for Hepatitis C Genotype 1 With Fatty Liver
Information source: Beth Israel Medical Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Hepatitis C Infection; Fatty Liver
Intervention: Rosiglitazone and Pegasys/Ribavirin (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: Beth Israel Medical Center Official(s) and/or principal investigator(s):
Douglas Meyer, M.D., Principal Investigator, Affiliation: Beth Israel Medical Center
Henry C. Bodenheimer, M.D., Study Director, Affiliation: Beth Israel Medical Center
Summary
To study the effectiveness and safety of adding Rosiglitazone, an insulin sensitizing agent
to people with chronic hepatitis C infection genotype 1 with fatty liver disease, who are
being treated with standard therapy. Standard therapy consists of weekly pegylated
interferon injections and daily ribavirin pills, whose dosage is weight based. This regimen
in genotype 1 patients is effective in only 45% of patients at best. In addition, this
therapy must be given for 48 weeks to be effective and has alot of side-effects. One risk
factor for a poor response is fatty liver. Rosiglitazone has been shown to be effective in
the treatment of patients with fatty liver alone. This study hopes to show that the addition
of Rosiglitazone to the standard therapy in genotype 1 patients with fatty liver disease will
increase effectiveness of the standard therapy of hepatitis C.
Clinical Details
Official title: Randomized Placebo-Control Pilot Study Evaluating the Efficacy and Safety of Rosiglitazone Combined With Pegylated Interferon Plus Ribavirin Versus Pegylated Interferon Plus Ribavirin Alone in Genotype 1 Hepatitis C With Steatosis
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: To compare the efficacy of Rosiglitazone in combination with pegylated interferon alfa-2a and ribavirin (weight-based) to that of pegylated interferon alfa-2a and ribavirin alone in terms of sustained viral response.
Secondary outcome: To compare the safety and tolerability of Rosiglitazone in combination with pegylated interferon-2a and ribavirin to that of pegylated interferon alfa-2a and ribavirin alone in terms of adverse events.
Detailed description:
Eligible thirty subjects will be randomized in a double blinded fashion to either
Rosiglitazone 4mg pills twice a day versus placebo for six weeks. Then after this six week
period, both groups will be treated for 48 weeks of standard therapy for hepatitis C
consisting of Pegasys 180mcq weekly injections with Ribavirin 1,000mg-1,200mg daily depending
if the subject weights less than 75 kg will then receive the lower dosage. In addition, the
subjects will be continued on Rosiglitazone or placebo for the 48 weeks.
The subjects will be monitored for side-effects by history taking and blood testing at
predetermined time periods during the study. If the viral load has not dropped more than two
log at week 12 of standard therapy for hepatitis C then therapy will be stopped and the
subject is considered a treatment failure. Similarly, if there was a greater than two log
drop in the viral load at week 12 but there is still virus present in the blood at week 24
then therapy is stopped and the subject is considered treatment failure. If the virus is
undetectable in the blood at week 12 and 24 then therapy is continued for the full 48 weeks.
If the virus is detectable at week 48 then the subject is considered a treatment failure.
After this 48 week treatment period and the virus is still undetectable, there is a follow-up
period consisting of 24 weeks off therapy. At the end of the 24 weeks, blood will be tested
for the virus and if the virus is not present then the subject has a sustained viral response
and is a treatment success.
During therapy if the subject becomes significantly anemic Procrit 40,000Units weekly
injections will be started. Similarly, if the white blood cell count drops below a certain
level then weekly Neupogen 300mcq injections will be started. In addition, if there is mild
depressive symptoms treatment will be started but if there is major depressive symptoms, then
therapy will be stopped and a referral to a psychiatrist will be made.
Eligibility
Minimum age: 21 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Men and women at least 21 years of age.
- Positive serum hepatitis C RNA for at least 6 months.
- Naive to any therapy for hepatitis C infection.
- Significant steatosis or fat on the liver biopsy.
- Genotype 1 patients.
Exclusion Criteria:
- Subjects with decompensated liver disease.
- Hemoglobin <12g/dl.
- WBC<2,000mm3.
- ANC<1,000mm3.
- Platelet count<50,000/mm3.
- Creatinine>1. 5mg/dl.
- Albumin<2. 5g/dl.
- Bilirubin>4mg/dl.
- HIV or hepatitis B co-infection.
- History of other liver disease besides fatty liver disease.
- History of unstable cardiac or cerebrovascular disease.
- History of significant psychiatric disorders.
- Alcohol or drug abuse within last year.
- Pregnant or lactating women or men whose sexual partner is pregnant or lactating.
- Taking of insulin or oral hypoglycemic agents within six months of the study.
- Uncontrolled thyroid disorder.
- History of malignancy within the past 5 years unless cured by surgery.
- History of autoimmune disorder or organ transplantations requiring immunosuppression.
Locations and Contacts
Beth Israel Medical Center - Philipps Ambulatory Care Center, New York, New York 10003, United States
Additional Information
Starting date: January 2006
Ending date: October 2007
Last updated: October 31, 2007
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