Study for the Treatment of Significant Steatosis With Xenical Followed by Treatment of Hepatitis C With Pegasys/Copegus - Full Text View

Sponsor:	The Geneva Foundation
Collaborator:	Hoffmann-La Roche
Information provided by:	Brooke Army Medical Center
ClinicalTrials.gov Identifier:	NCT00207311

Purpose

This is a prospective, multi-center, randomized, placebo-controlled trial in subjects with histological evidence of > 33% hepatic steatosis or nonalcoholic steatohepatitis (NASH) and chronic hepatitis C. Patients who have not been previously treated for hepatitis C (treatment naive) will be enrolled.

Condition	Intervention	Phase
Fatty Liver Hepatitis C	Drug: Xenical (or Placebo), Pegasys, Copegus Behavioral: Xenicare Program	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Multi-Centered, Prospective, Randomized, Placebo-Controlled Clinical Trial for the Treatment of Significant Steatosis or NASH With Xenical Followed by Treatment of Hepatitis C (HCV) With PEG-Interferon Alpha-2a/Copegus

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Ribavirin Orlistat Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Brooke Army Medical Center:

Primary Outcome Measures:

Sustained virological response (SVR) defined as the percentage of participants with undetectable HCV-RNA as measured by the Roche AMPLICORTM HCV Test, v 2.0 (detection limit 50 IU/mL) at 24 weeks post completion of the treatment period [ Time Frame: 110 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Hepatic steatosis, necroinflammatory activity and fibrosis improvement at week 36 as determined by Dr. Elizabeth Brunt at Saint Louis University [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	August 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Xenical placebo PO three times daily with meals plus enrollment into the Xenicare program for 36 weeks followed by 48 weeks of therapy with Pegasys (180mcg/ml) plus weight based ribavirin for HCV genotype 1 or 4 and 24 weeks of therapy with Pegasys (180mcg/ml) plus 800mg ribavirin for HCV genotypes 2 and 3.	Drug: Xenical (or Placebo), Pegasys, Copegus Xenical 120mg three times daily for 36 weeks or xenical placebo (Arm 1). Pegasys 180 mcg weekly for 48 weeks. Ribavirin daily for 48 weeks. Behavioral: Xenicare Program Xenicare program for 36 weeks.
2: Active Comparator Xenical (orlistat) 120mg PO three times daily with meals plus enrollment into the Xenicare program for 36 weeks followed by 48 weeks of therapy with Pegasys (180mcg/ml) plus weight based ribavirin for HCV genotype 1 or 4 and 24 weeks of therapy with Pegasys (180mcg/ml) plus 800mg ribavirin for HCV genotypes 2 and 3.	Drug: Xenical (or Placebo), Pegasys, Copegus Xenical 120mg three times daily for 36 weeks or xenical placebo (Arm 1). Pegasys 180 mcg weekly for 48 weeks. Ribavirin daily for 48 weeks. Behavioral: Xenicare Program Xenicare program for 36 weeks.

Detailed Description:

Recent evidence suggests that patients with concomitant chronic HCV infection and NASH or significant hepatic steatosis (>33%) respond less well to standard antiviral therapy. As previously noted, up to 10% of patients with chronic HCV infection will have concomitant NASH and an even greater percentage will have associated hepatic steatosis. No prospective studies to date have evaluated the sustained viral response rates to standard antiviral therapy in this group of patients who were previously treated with a medication to eliminate or improve the underlying NASH and/or hepatic steatosis.

Primary Outcome: To determine if decreasing the amount of NASH or hepatic steatosis in overweight (BMI >27 kg/m2) HCV patients results in improved overall SVR to PEGASYS and Copegus.

Secondary Outcome: 1.To determine the amount of steatosis, necroinflammatory activity, and fibrosis change in a group of participants with chronic hepatitis C and NASH or significant steatosis treated with Xenical vs. placebo for 36 weeks. 2. To assess for a difference in insulin resistance, as measured by the QUICKI score, before and after treatment with Xenical or Xenical placebo and diet and exercise.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Participants must be willing to give written informed consent and be 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-Ab or HCV-RNA by PCR Positive for at least 6 months
Serum positive for HCV-RNA by PCR assay
Treatment naïve participants who have hepatitis C with genotype 1, 2, 3, or 4
Body mass index (BMI) >27
Liver biopsy within 12 months prior to enrollment with a pathology report confirming the histological diagnosis consistent with chronic hepatitis and NASH or hepatic steatosis of >33%
Compensated liver disease with minimum hematological, biochemical, and serologic criteria at the Enrollment Visit (WNL = within normal limits):
- Hemoglobin values of <12 gm/dL for females and <13 gm/dL for males
- WBC <3,000/ mm3
- Neutrophil count < 1,500/mm3
- Platelets <65,000/ mm3
- Direct bilirubin within 20% of ULN
- Indirect bilirubin WNL
- Albumin > 3 gm/dL
- creatinine < 20% of ULN
- TSH WNL
- Alpha fetoprotein value < 100 ng/mL
Reconfirmation and documentation that sexually active female subjects of childbearing potential are practicing adequate contraception method, or monogamous relationship with a male partner who has had a vasectomy or is using a condom + spermicide) during the treatment period and for six months following the last dose of study medication
Reconfirmation that sexually active male subjects are practicing two acceptable methods of contraception

Exclusion Criteria:

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
Hepatitis C of non-genotype 1,2,3 or 4
Previous anti-viral therapy for treatment of Hepatitis C
Suspected hypersensitivity to interferon, PEG-interferon, ribavirin, Xenical
Any other cause for liver disease other than chronic hepatitis C and NASH or steatosis, including but not limited to:
- Hemochromatosis
- Alpha-1 antitrypsin deficiency
- Co-infection with HBV
- Wilson's disease
- Autoimmune hepatitis
- Alcoholic liver disease
- Drug-related liver disease
Any condition that would prevent the subject from having a liver biopsy
Hemoglobinopathies (e.g., Beta Thalassemia)
Evidence of advanced liver disease
Patients 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 are excluded
- CNS trauma or preexisting/active seizure disorders uncontrolled with medication
- Significant cardiovascular dysfunction within the past 12 months
- Poorly controlled diabetes mellitus
- Chronic pulmonary disease with documented pulmonary hypertension
- Immunologically mediated disease (Crohn's disease, ulcerative colitis), rheumatoid arthritis, idiopathic thrombocytopenia purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, clinical cryoglobulinemia with vasculitis
Any medical condition requiring, or likely to require chronic systemic administration of steroids
Evidence of an active or suspected cancer or a history of malignancy where the risk of reoccurrence is ≥ 20% within 2 years
Active clinical gout
Substance abuse, such as alcohol, IV drugs and inhaled drugs
Participants not willing to be counseled/abstain from alcohol
Participants with clinically severe retinal abnormalities
Any other condition that in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the protocol
Known positive HIV
Inability/unwillingness to provide informed consent or abide by the requirements of the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00207311

Locations

United States, Texas
Brooke Army Medical Center
Ft. Sam Houston, Texas, United States, 78234

Sponsors and Collaborators

The Geneva Foundation

Hoffmann-La Roche

Investigators

Principal Investigator:

Stephen A Harrison, MD

Brooke Army Medical Center

More Information

No publications provided

Responsible Party:	Brooke Army Medical Center ( Stephen Harrison, MD )
Study ID Numbers:	C.2004.140
Study First Received:	September 13, 2005
Last Updated:	June 22, 2009
ClinicalTrials.gov Identifier:	NCT00207311 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Brooke Army Medical Center:

Hepatitis C
Fatty Liver
NASH
Steatohepatitis

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Liver Diseases
RNA Virus Infections
Molecular Mechanisms of Pharmacological Action
Flaviviridae Infections
Ribavirin
Hepatitis, Viral, Human
Enzyme Inhibitors
Fatty Liver
Antiviral Agents

Pharmacologic Actions
Hepatitis
Virus Diseases
Anti-Obesity Agents
Orlistat
Digestive System Diseases
Therapeutic Uses
Peginterferon alfa-2a
Hepatitis C
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010