Chronic Hepatitis CNCT00571714
Pilot Comparison of Standard Antiviral Therapy With and Without 12 Weeks of Betaine in Genotype 1 Naive Patients
A study testing Peginterferon alpha-2a and ribavirin and Peginterferon alpha-2a , ribavirin and betaine in people with Chronic Hepatitis C, run by University of Nebraska.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 70 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Peginterferon alpha-2a and ribavirin and Peginterferon alpha-2a , ribavirin and betaine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2008to 4 Mar 2010
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 11Show fewer
- 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.
Who cannot join
- 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
Show all 16Show fewer
- 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.
About this study
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
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.
Read the 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).
- Conditions
- Chronic Hepatitis C
- Being tested
- Peginterferon alpha-2a and ribavirin, Peginterferon alpha-2a , ribavirin and betaine
- Keywords
- Chronic hepatitis C, Pilot Comparison, Peginterferon alph-2a, Ribavirin, Betaine, Genotype 1, Treatment naive
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon alpha-2a and ribavirinDrug
Also called Pegasys, Copegus
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
Peginterferon alpha-2a , ribavirin and betaineDrug
Also called Pegasys, Copegas
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 Standard Peginterferon alpha-2a plus Rivavirin Therapy | Active comparator | Peginterferon alpha-2a once a week plus weight based ribavirin (800-1400mg/day)in 2 divided daily doses Receives: Drug: Peginterferon alpha-2a and ribavirin |
| 2 Peginterferon alpha-2a plus Rivavirin Therapy with Betaine for First 12 Weeks | Active comparator | 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 Receives: Drug: Peginterferon alpha-2a , ribavirin and betaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Viral Response 24 weeks following the end of anti-viral therapy
no patients enrolled
Measured: 72 weeks
Secondary outcomes (4)
Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy
no patients enrolled
Measured: 12 weeks
Comparison of the safety of the two treatment regimens
no patients enrolled
Measured: 48 weeks
Comparison of ALT normalization between the two regimens
no patients enrolled
Measured: 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.
no patients enroll
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2007 (estimated)
- Study start1 Apr 2008
- Primary completion4 Mar 2010
- Study completion4 Mar 2010
Why it stopped: lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark E Mailliard, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571714
- Sponsor's protocol ID
- 0159-07-FB
- Status last verified
- Aug 2023
- First submitted
- 11 Dec 2007
- Last updated
- 15 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: no patients enrolled to the study
Publications
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.
PubMed 11569700Duong 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.
PubMed 165575518. 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.
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00571714
- Acronym / sponsor ID
- 0159-07-FB
- Conditions
- Chronic Hepatitis C
- Keywords
- Chronic hepatitis C, Pilot Comparison, Peginterferon alph-2a, Ribavirin, Betaine, Genotype 1, Treatment naive
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 Apr 2008 (actual)
- Primary completion
- 4 Mar 2010 (actual)
- Study completion
- 4 Mar 2010 (actual)
- First posted
- 12 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Standard Peginterferon alpha-2a plus Rivavirin Therapy | Active comparator | Drug: Peginterferon alpha-2a and ribavirinPeginterferon alpha-2a once a week plus weight based ribavirin (800-1400mg/day)in 2 divided daily doses |
| 2 Peginterferon alpha-2a plus Rivavirin Therapy with Betaine for First 12 Weeks | Active comparator | Drug: Peginterferon alpha-2a , ribavirin and betainePeginterferon 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 |
Who may qualify
- Ages
- 19 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Peginterferon alpha-2a and ribavirinAlso: Pegasys, CopegusPeginterferon 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 | Drug | 1 Standard Peginterferon alpha-2a plus Rivavirin Therapy |
| Peginterferon alpha-2a , ribavirin and betaineAlso: Pegasys, CopegasPeginterferon 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. | Drug | 2 Peginterferon alpha-2a plus Rivavirin Therapy with Betaine for First 12 Weeks |
Primary outcome
Sustained Viral Response 24 weeks following the end of anti-viral therapy
Time frame: 72 weeks
no patients enrolled
4 secondary outcomes
Comparison of rapid and early virologic response in the first 4 and 12 weeks of therapy
Time frame: 12 weeks
Comparison of the safety of the two treatment regimens
Time frame: 48 weeks
Comparison of ALT normalization between the two regimens
Time frame: 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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2023.
- Background: PubMed 11569700Abdelmalek 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.
- Background: PubMed 16557551Duong 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 publication8. 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.
- Individual participant dataSharing planned: No. no patients enrolled to the study
Related trials for Chronic Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark E Mailliard, MD principal investigator
University of Nebraska
Questions about this trial
What is this clinical trial studying?
A study testing Peginterferon alpha-2a and ribavirin and Peginterferon alpha-2a , ribavirin and betaine in people with Chronic Hepatitis C, run by University of Nebraska.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sustained Viral Response 24 weeks following the end of anti-viral therapy (time frame: 72 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00571714, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.