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

August 11, 2023 updated by: University of Nebraska

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Nebraska Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1 Standard Peginterferon alpha-2a plus Rivavirin Therapy
Peginterferon alpha-2a once a 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 plus Rivavirin Therapy with Betaine for First 12 Weeks
Peginterferon alpha-2a once a 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sustained Viral Response 24 weeks following the end of anti-viral therapy
Time Frame: 72 weeks
no patients enrolled
72 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy
Time Frame: 12 weeks
no patients enrolled
12 weeks
Comparison of the safety of the two treatment regimens
Time Frame: 48 weeks
no patients enrolled
48 weeks
Comparison of ALT normalization between the two regimens
Time Frame: 48 weeks
no patients enrolled
48 weeks
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
no patients enroll
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Investigators

  • Principal Investigator: Mark E Mailliard, MD, University of Nebraska

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2008

Primary Completion (Actual)

March 4, 2010

Study Completion (Actual)

March 4, 2010

Study Registration Dates

First Submitted

December 11, 2007

First Submitted That Met QC Criteria

December 11, 2007

First Posted (Estimated)

December 12, 2007

Study Record Updates

Last Update Posted (Actual)

August 15, 2023

Last Update Submitted That Met QC Criteria

August 11, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0159-07-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

no patients enrolled to the study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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