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

Primary Purpose

Chronic Hepatitis C

Status

Withdrawn

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Peginterferon alpha-2a and ribavirin

Peginterferon alpha-2a , ribavirin and betaine

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Chronic hepatitis C, Pilot Comparison, Peginterferon alph-2a, Ribavirin, Betaine, Genotype 1, Treatment naive

Eligibility Criteria

19 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

1 Standard Peginterferon alpha-2a plus Rivavirin Therapy

2 Peginterferon alpha-2a plus Rivavirin Therapy with Betaine for First 12 Weeks

Arm Description

Peginterferon alpha-2a once a week plus weight based ribavirin (800-1400mg/day)in 2 divided daily doses

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

Outcomes

Primary Outcome Measures

Sustained Viral Response 24 weeks following the end of anti-viral therapy

no patients enrolled

Secondary Outcome Measures

Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy

no patients enrolled

Comparison of the safety of the two treatment regimens

no patients enrolled

Comparison of ALT normalization between the two regimens

no patients enrolled

Comparison of the effect on interferon gene signaling in peripheral blood mononuclear cells between the two regimens in the first 12 weeks of therapy.

no patients enroll

Full Information

NCT ID

NCT00571714

First Posted

December 11, 2007

Last Updated

August 11, 2023

Sponsor

University of Nebraska

1. Study Identification

Unique Protocol Identification Number

NCT00571714

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Withdrawn

Why Stopped

lack of enrollment

Study Start Date

April 1, 2008 (Actual)

Primary Completion Date

March 4, 2010 (Actual)

Study Completion Date

March 4, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Nebraska

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C

Keywords

Chronic hepatitis C, Pilot Comparison, Peginterferon alph-2a, Ribavirin, Betaine, Genotype 1, Treatment naive

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1 Standard Peginterferon alpha-2a plus Rivavirin Therapy

Arm Type

Active Comparator

Arm Description

Peginterferon alpha-2a once a week plus weight based ribavirin (800-1400mg/day)in 2 divided daily doses

Arm Title

2 Peginterferon alpha-2a plus Rivavirin Therapy with Betaine for First 12 Weeks

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Peginterferon alpha-2a and ribavirin

Other Intervention Name(s)

Pegasys, Copegus

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Peginterferon alpha-2a , ribavirin and betaine

Other Intervention Name(s)

Pegasys, Copegas

Intervention Description

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.

Primary Outcome Measure Information:

Title

Sustained Viral Response 24 weeks following the end of anti-viral therapy

Description

no patients enrolled

Time Frame

72 weeks

Secondary Outcome Measure Information:

Title

Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy

Description

no patients enrolled

Time Frame

12 weeks

Title

Comparison of the safety of the two treatment regimens

Description

no patients enrolled

Time Frame

48 weeks

Title

Comparison of ALT normalization between the two regimens

Description

no patients enrolled

Time Frame

48 weeks

Title

Comparison of the effect on interferon gene signaling in peripheral blood mononuclear cells between the two regimens in the first 12 weeks of therapy.

Description

no patients enroll

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark E Mailliard, MD

Organizational Affiliation

University of Nebraska

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

no patients enrolled to the study

Citations:

PubMed Identifier

11569700

Citation

Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001 Sep;96(9):2711-7. doi: 10.1111/j.1572-0241.2001.04129.x.

Results Reference

background

PubMed Identifier

16557551

Citation

Duong FH, Christen V, Filipowicz M, Heim MH. S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro. Hepatology. 2006 Apr;43(4):796-806. doi: 10.1002/hep.21116.

Results Reference

background

Citation

8. Mukherjee S, Bernard T, Schafer D, et al. Impact of betaine on hepatic fibrosis and homocysteine in nonalcoholic steatohepatitis: a prospective cohort study [abstract]. Hepatology 2005; 42: 610A.

Results Reference

result

Learn more about this trial

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

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