The primary purpose of the study is to compare the safety and effectiveness of standard
treatment for chronic hepatitis C using peginterferon alpha-2a (Pegasys) and ribavirin
(Copegus) to those same medications plus a dietary supplement called betaine when added for
the first 12 weeks of treatment.
Peginterferon alpha-2a (Pegasys) and ribavirin (Copegus) are approved by the FDA (Food and
Drug Administration) for the treatment of chronic hepatitis C.
Betaine is a dietary supplement and occurs naturally in the body. It is not a medication
regulated by the FDA or an approved drug for chronic hepatitis C.
Although pegylated alpha interferon and ribavirin will likely be part of the core therapy
for chronic HCV for the next several years, there are a number of complimentary antiviral
agents in development including protease or polymerase inhibitors, RNA vaccines and
immunomodulators (5). However, it would be unlikely to have FDA approval for any of these
newer agents before the next 3 - 5 years, i.e. 2010-2012.
Betaine, a naturally occurring anti-oxidant metabolite of choline and an amino acid analog
(tri-methyl-glycine), serves as a methylation agent to re-methylate damaged cell proteins or
enzymes (6). By virtue of its metabolic role in decreasing toxic metabolites, betaine also
protects against alcohol-induced fatty liver and apoptosis. Recently, pilot studies
performed both at the Mayo Clinic and here at UNMC showed its applicability as a treatment
of non-alcoholic fatty liver in human subjects (7, 8).
Betaine has also recently been found to promote interferon function by overcoming HCV -
induced inhibition of interferon signaling (9). Naturally-occurring HCV proteins during
human infection can hypo-methylate proteins integral to the Jak - STAT (signal transducers
and activators of transcription) pathway, thereby inhibiting the antiviral activity of
interferon. In cultured cells betaine administration, in a physiologically attainable
concentration, restored STAT methylation and improved interferon signaling (9).
- Subject must be willing to give informed consent and be able to adhere to dose and
- History of chronic hepatitis C as documented by either anti-HCV or HCV RNA
- Adult subjects 19-70 years of age, of either gender
- Liver biopsy within 3 years prior to the screening 1 visit.
- 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 -
- Fasting glucose should be 70 -140 mg/dl, results between 116-140 require a HbA1c <
- 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.
- 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
- History of new hepatitis C exposure within the last 6 months
- Prior treatment for chronic hepatitis C.
- 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
- Treatment with any investigational drug within 30 days of Screening visit 1.
- Any other cause for liver disease other than CHC.
- Coagulopathies including hemophilia
- G6PD deficiency
- 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
- 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.