Pilot Comparison of Standard Antiviral Therapy With and Without 12 Weeks of Betaine in Genotype 1 Naive Patients

This study has been terminated.
(lack of enrollment)
Sponsor:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00571714
First received: December 11, 2007
Last updated: June 23, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention
Chronic Hepatitis C
Drug: Peginterferon alpha-2a and ribavirin
Drug: Peginterferon alpha-2a , ribavirin and betaine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Standard Therapy,Peginterferon Alpha-2a + Ribavirin for 48 Weeks VS Peginterferon Alph-2a + Ribavirin + Betaine for 12 Weeks Followed by 36 Weeks Standard Therapy in Untreated Adults With Chronic Hepatitis C Genotype 1

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Sustained Viral Response 24 weeks following the end of anti-viral therapy [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Comparison of the safety of the two treatment regimens [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Comparison of ALT normalization between the two regimens [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Comparison of the effect on interferon gene signaling in peripheral blood mononuclear cells between the two regimens in the first 12 weeks of therapy. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: April 2008
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Peginterferon alpha-2a q week plus weight based ribavirin (800-1400mg/day)in 2 divided daily doses
Drug: Peginterferon alpha-2a and ribavirin
Peginterferon alpha-2a 180mcg by subcutaneous injection every week and weight based ribavirin, 800 to 1400mg/day by mouth in two divided doses every day for 48 weeks
Other Names:
  • Pegasys
  • Copegus
Active Comparator: 2
Peginterferon alpha-2a q week plus weight based ribavirin (800-1400mg/day) in 2 divided daily doses plus betaine (20gm/day) in 2 divided doses for 12 weeks followed by Peginterferon alpha-2a q week plus weight based ribavirin (800-1400mg/day) in 2 divided daily doses for 36 weeks
Drug: Peginterferon alpha-2a , ribavirin and betaine
Peginterferon alpha-2a 180mcg given by subcutaneous injection every week plus weight based ribavirin 800 to 1400 mg/day by mouth in divided doses twice a day plus betaine 10 gm dissolved in juice twice a day for twelve weeks followed by peginterferon alpha-2a 180 mcg given by subcutaneous injection every week plus weight based ribavirin 800 to 1400mg/day by mouth in divided doses twice a day for 36 weeks.
Other Names:
  • Pegasys
  • Copegas

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   19 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 as documented by either anti-HCV or HCV RNA positivity.
  • 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 - 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.
  • 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
  • Hemoglobinopathies
  • 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571714

Locations
United States, Nebraska
Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Mark E Mailliard, M.D. University of Nebraska
  More Information

Publications:
Responsible Party: Mark Mailliard, M.D., University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00571714     History of Changes
Other Study ID Numbers: 159-07-FB
Study First Received: December 11, 2007
Last Updated: June 23, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
Chronic hepatitis C
Pilot Comparison
Peginterferon alph-2a
Ribavirin
Betaine
Genotype 1
Treatment naive

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Betaine
Interferon-alpha
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Gastrointestinal Agents
Hypolipidemic Agents
Immunologic Factors
Lipid Regulating Agents
Lipotropic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014