Pilot Study of Betaine + Combination Antiviral Therapy for Chronic Hepatitis C Genotype 1 Non-responder/Relapsers

• Status: Terminated
• Trial end date: 2011-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a non-randomized, open-label study examining the safety and efficacy of betaine in addition to standard anti-viral therapy in genotype 1 hepatitis C non-responders or relapsers to previous pegylated interferon plus ribavirin. Betaine (20 gm/day) in 2 divided doses will be added to Peginterferon alpha 2a (180 mcg) plus weight-based Ribavirin (1000 or 1200 mg/day, for body weight < or > 75 kg, respectively, for 48 weeks. Patients must be diagnosed with chronic hepatitis C, genotype I, and have undergone therapy for hepatitis C with pegylated interferon plus ribavirin. Subjects will be followed for safety, tolerability, hepatitis C viral response and the effect on interferon gene signaling in peripheral blood mononuclear cells during therapy.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Nebraska
• Treatments: Betaine; Interferon-alpha; Peginterferon alfa-2a; Ribavirin

Criteria

Inclusion Criteria:

• Subject must be willing to give informed consent and be able to adhere to dose and visit schedules.

• History of chronic hepatitis C, genotype 1, non-responders or relapsers as documented by genotype testing and HCV RNA levels at 12 weeks ( < 2 log change) during therapy or at 3 - 12 months post therapy, respectively.

• Adult subjects 18-70 years of age, of either gender

• Liver biopsy within 3 years prior to the screening 1 visit with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis C.

• Compensated liver disease with the following maximum hematologic, biochemical and serologic criteria at the Screening visit (WNL=within normal limits) Hemoglobin > 12 g/dl for females and >13 g/dl for males, WBC > 3000/mm3, Platelets > 80,000/mm3, Direct Bilirubin - WNL. Indirect bilirubin - WNL, Albumin - WNL, Serum Creatinine - WNL.

• Fasting glucose should be 70 -140 mg/dl, results between 116-140 require a HbA1c < 8.5%

• TSH - WNL

• Subjects with a history of mild depression may be considered for entry in to this study provided that a pretreatment assessment of the subject's affective status supports that the subject is clinically stable.

• Subjects with a history of substance abuse must have abstained from using the substance for at least one year prior to the Screening visit.

• Antinuclear antibodies (ANA) < 1:320

• No radiologic evidence of a focal mass suggestive of hepatoma and/or ascites.

Exclusion Criteria:

• Pregnant or nursing subjects. Subjects who intend to become pregnant during the study period. Subjects with partners who intend to become pregnant during the study period.

• Prior response to therapy and failure to achieve SVR which may have been due to treatment non-compliance, in the assessment of the investigator based upon subject's medical history.

• Participation in any clinical trial of a HCV protease inhibitor of any duration. Subjects may have received other investigational agents for the treatment of HCV, as long as they have also received an adequate course of Peg-IFN/RBV [i.e., the investigational agent could not have replaced either Peg-IFN (such as Albuferon) or RBV (viramidine)].

• History of new hepatitis C exposure within the last 6 months

• Current or intended use of G-CSF and/or GM-CSF during the stud period is prohibited. Current use of erythropoietin (EPO) is prohibited.

• Suspected hypersensitivity to any interferon product or ribavirin

• Participation in any other clinical trial within 30 days of Screening visit 1

• Treatment with any investigational drug within 30 days of Screening visit 1.

• Any other cause for liver disease other than CHC, including but not limited to:

hemachromatosis, Alpha-1 antitrypsin deficiency, Wilson's disease, Autoimmune hepatitis, Alcoholic liver disease, Non-alcoholic steatohepatitis (NASH), Drug-related liver disease

• Known coagulopathies including hemophilia

• Known hemoglobinopathies

• Known G6PD deficiency

• Known coinfection with HIV and/or HBV

• Evidence of active or suspected malignancy or a history of malignancy within the last five years (with the exception of adequately treated basal cell carcinoma of the skin).

• Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices or hepatic encephalopathy

• Subjects with organ transplants other than cornea or hair transplant

• Any Known preexisting medical condition, that could interfere with the subject's participation in and completion of the study including, but not limited to moderate to severe depression, or a history of severe psychiatric disorder, such as psychosis, suicidal ideation and/or suicidal attempt; Subjects with a past history or current use of lithium and/or antipsychotic drugs; CNS trauma or seizure disorder; Clinically significant ECG abnormalities and/or significant cardiovascular dysfunction within the past 2 years prior to Screening ; Poorly controlled diabetes mellitis; Chronic pulmonary disease (COPD); Immunologically mediated disease such as inflammatory bowel disease, rheumatoid arthritis, idiopathic thrombocytopenia purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis or symptomatic thyroid disorder; Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids: History of, or active clinical gout.

• Substance abuse, such as alcohol (>80 g/day), IV drugs and inhaled drugs. Subjects with a history of substance abuse must have abstained from the abuse substance for at least one year. Subjects with clinically significant retinal abnormalities

• Any other condition which in the opinion of the investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in and completing the protocol

• Subjects who are part of the staff personnel directly involved with the study

• Subjects who are immediate family members of the investigational study staff