Clinical trial NCT00207402: Infergen, Ribavirin & Avandia in Previous Relapsers or Nonresponders to Pegylated Interferon and Ribavirin
Official title: A Pilot Trial of Combination Therapy With Interferon Alfacon1, Ribavirin, & Rosiglitazone in a Group of Insulin Resistant, Chronic Hepatitis C, GT 1 Patients Who Are Previous Relapsers or Nonresponders to Pegylated Interferon and Ribavirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Keywords: Hepatitis C
Insulin resistance
Lead sponsor: Brooke Army Medical Center
Sponsor class: FED
Collaborators: name: InterMune
First posted: 2005-09-21
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Genotype 1 hepatitis C virus (HCV) patients who did not respond (did not lose virus during treatment) or relapsed (virus went away on treatment but came back after treatment was stopped) after treatment with at least twelve weeks of a pegylated (long-acting) interferon and ribavirin will be considered for this study. There are two purposes to this study: first, to determine how rosiglitazone, a medicine used to treat diabetes, affects the HCV viral load; and second, to determine if treatment of insulin resistance with rosiglitazone prior to therapy for HCV will improve sustained virologic response (loss of virus that continues beyond six months after completion of HCV therapy) to HCV therapy.

Detailed description: This study will demonstrate the efficacy of treating insulin resistance with rosiglitazone in CHC, genotype 1 patients who have failed previous treatment with pegylated interferon and ribavirin. Pre-treatment with rosiglitazone may become the new standard of care prior to HCV therapy for those patients who are insulin resistant, increasing their chance for achieving an SVR on interferon alfacon-1 combination therapy and decreasing the morbidity and mortality associated with chronic hepatitis C.

Eligibility criteria: Inclusion Criteria:

* Participants willing to give written informed consent and able to adhere to dose and visit schedules.
* Adult participants 18 years of age or older of either gender or any race. Participants who are over 65 years of age must be in generally good health.
* HCV-antibody (Ab) or HCV-RNA positive by polymerase chain reaction (PCR) for at least 6 months.
* Serum positive for HCV-RNA by PCR assay.
* Subjects must be previous nonresponders or relapsers on pegylated interferon and ribavirin therapy.
* Liver biopsy within 24 months prior to enrollment into the protocol.
* Compensated liver disease with the following minimum hematological, biochemical, and serologic criteria at the Screening Visit (WNL = within normal limits):

  * Hemoglobin values of \< 12 gm/dL for females and \< 13 gm/dL for males.
  * White blood cells (WBC) \< 3,000/mm3
  * Neutrophil count \< 1,500/mm3
  * Platelets \< 65,000/mm3
  * Direct bilirubin, within 20% of upper limits of normal (ULN)
  * Indirect bilirubin, (WNL) (unless non-hepatitis related factors such as Gilbert's disease explain an indirect bilirubin rise. In such cases indirect bilirubin must be \< 3.0 mg/dL \[\< 51.3 µmol/L\]).
  * Albumin \> 3 gm/dL
  * Serum creatinine \< 20% of ULN
  * Thyroid stimulating hormone (TSH) WNL
  * Alpha fetoprotein value \< 100 ng/mL.
* Reconfirmation and documentation that sexually active female subjects of childbearing potential are practicing adequate contraception during the treatment period and for 6 months following the last dose of study medication. Female subjects must not be breast-feeding.
* Reconfirmation that sexually active male subjects are practicing two acceptable methods of contraception during the treatment period and for 6 months following the last dose of study medication.

Exclusion Criteria:

* Inability or unwillingness to provide informed consent or abide by the requirements of the study
* Participants on insulin are excluded.
* Participants on metformin or another thiazolidinedione must have a three-month wash-out period to be considered for the study.
* Women who are pregnant or breast-feeding
* Males whose female partner is pregnant
* No other thiazolidinedione after liver biopsy and/or during the entire study (other than those subjects randomized to receive rosiglitazone during the study)
* Hepatitis C of non-genotype 1
* Suspected hypersensitivity to interferon, ribavirin, or rosiglitazone
* Any cause for liver disease other than chronic hepatitis C, insulin resistance, or non-alcoholic fatty liver disease (NAFLD), including but not limited to:

  * Hemochromatosis
  * Alpha-1 antitrypsin deficiency
  * Co-infection with hepatitis B virus (HBV) \[serum hepatitis B surface antigen (HBsAg) positive\]
  * Wilson's disease
  * Autoimmune hepatitis
  * Alcoholic liver disease (consumption of greater than 2 drinks a day on average)
  * Drug-related liver disease
* Any condition that would prevent the subject from having a liver biopsy.
* Hemoglobinopathies that could potentially compromise patient safety (e.g., beta thalassemia major, sickle cell disease)
* Evidence of advanced liver disease
* Participants with organ transplants other than cornea and hair transplant
* Any known preexisting medical condition that could interfere with the subject's participation in and completion of the protocol such as:

  * Preexisting psychiatric condition, especially severe depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt.
  * Participants with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject's mental status supports that the participant is clinically stable.

Primary outcomes:
measure: There is change in viral kinetics with improvement of insulin sensitivity
timeFrame: 104 days
Secondary outcomes:
measure: There is significant improvement in the SVR obtained when treating insulin resistant patients with the insulin sensitizing medication, Avandia, prior to and during treatment with Infergen and ribavirin when compared to Infergen
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Ft. Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
Study officials:
affiliation: Brooke Army Medical Center
name: Stephen A Harrison, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brooke Army Medical Center
name: Shane Mills, MD
role: PRINCIPAL_INVESTIGATOR
References: