Chronic Hepatitis CEarly Phase 1NCT00882193
Pilot Study of Betaine + Combination Antiviral Therapy for Chronic Hepatitis C Genotype 1 Non-responder/Relapsers
A Early Phase 1 study testing Betaine, Peginterferon alpha 2a and Ribavirin in people with Chronic Hepatitis C and Genotype 1, run by University of Nebraska at 1 site in United States.
Trial summary
This is a non-randomized, open-label study examining the safety and efficacy of betaine in addition to standard anti-viral therapy in genotype 1 hepatitis C non-responders or relapsers to previous pegylated interferon plus ribavirin. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Chronic Hepatitis C, Genotype 1, Relapse
- What is being tested?
- Betaine, Peginterferon alpha 2a and Ribavirin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2009to 12 Jan 2011
- Phase
- Early Phase 1
- 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 years and older
- 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, genotype 1, non-responders or relapsers as documented by genotype testing and HCV RNA levels at 12 weeks ( < 2 log change) during therapy or at 3 - 12 months post therapy, respectively.
- Adult subjects 18-70 years of age, of either gender
- Liver biopsy within 3 years prior to the screening 1 visit with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis C.
- 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%
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- 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.
- Prior response to therapy and failure to achieve SVR which may have been due to treatment non-compliance, in the assessment of the investigator based upon subject's medical history.
- Participation in any clinical trial of a HCV protease inhibitor of any duration. Subjects may have received other investigational agents for the treatment of HCV, as long as they have also received an adequate course of Peg-IFN/RBV [i.e., the investigational agent could not have replaced either Peg-IFN (such as Albuferon) or RBV (viramidine)].
- History of new hepatitis C exposure within the last 6 months
- 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
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- Participation in any other clinical trial within 30 days of Screening visit 1
- Treatment with any investigational drug within 30 days of Screening visit 1.
- Any other cause for liver disease other than CHC, including but not limited to: hemachromatosis, Alpha-1 antitrypsin deficiency, Wilson's disease, Autoimmune hepatitis, Alcoholic liver disease, Non-alcoholic steatohepatitis (NASH), Drug-related liver disease
- Known coagulopathies including hemophilia
- Known hemoglobinopathies
- Known G6PD deficiency
- Known 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 including, but not limited to moderate to severe depression, or a history of severe psychiatric disorder, such as psychosis, suicidal ideation and/or suicidal attempt; Subjects with a past history or current use of lithium and/or antipsychotic drugs; CNS trauma or seizure disorder; Clinically significant ECG abnormalities and/or significant cardiovascular dysfunction within the past 2 years prior to Screening ; Poorly controlled diabetes mellitis; Chronic pulmonary disease (COPD); Immunologically mediated disease such as inflammatory bowel disease, rheumatoid arthritis, idiopathic thrombocytopenia purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis or symptomatic thyroid disorder; Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids: History of, or active clinical gout.
- Substance abuse, such as alcohol (>80 g/day), IV drugs and inhaled drugs. Subjects with a history of substance abuse must have abstained from the abuse substance for at least one year. Subjects with clinically significant retinal abnormalities
- Any other condition which in the opinion of the investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in and completing the protocol
- Subjects who are part of the staff personnel directly involved with the study
- Subjects who are immediate family members of the investigational study staff
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Pilot Therapy Using Betaine in Combination With Peginterferon Alpha-2a Plus Ribavirin in Subjects With Genotype 1 Hepatitis C Who Have Not Achieved a Sustained Viral Response With a Prior Course of Pegylated Interferon and Ribavirin
This is a non-randomized, open-label study examining the safety and efficacy of betaine in addition to standard anti-viral therapy in genotype 1 hepatitis C non-responders or relapsers to previous pegylated interferon plus ribavirin. Betaine (20 gm/day) in 2 divided doses will be added to Peginterferon alpha 2a (180 mcg) plus weight-based Ribavirin (1000 or 1200 mg/day, for body weight < or > 75 kg, respectively, for 48 weeks. Patients must be diagnosed with chronic hepatitis C, genotype I, and have undergone therapy for hepatitis C with pegylated interferon plus ribavirin. Subjects will be followed for safety, tolerability, hepatitis C viral response and the effect on interferon gene signaling in peripheral blood mononuclear cells during therapy.
Read the detailed description
The primary objective is to examine the safety and efficacy of the betaine when combined with standard anti-viral therapy in previously treated adult subjects with chronic hepatitis C infected with genotype 1. The efficacy will be determined through comparison of the sustained viral response (SVR) to our protocol three-drug regimen (Betaine, Peginterferon plus Ribavirin) to that historically seen in relapsers and non-responders when retreated with standard therapy (Peginterferon and Ribavirin alone).
Secondary objectives include: (1) the comparison of the occurrence of rapid and early virologic response in the first 4 (Rapid Virologic Response, RVR) and 12 (Early Virologic Response, EVR) weeks of therapy, respectively, between the study regimen and historically treated patients. (2) the comparison of ALT normalization between the two groups. and (3) the effect on interferon gene signaling in peripheral blood mononuclear cells (PBMCs) between the two groups in the first 12 weeks of therapy and 6 months following the end of therapy.
- Conditions
- Chronic Hepatitis C, Genotype 1, Relapse
- Being tested
- Betaine, Peginterferon alpha 2a, Ribavirin
- Keywords
- Chronic hepatitis C, Genotype 1, Nonresponder, Relapser, Betaine, Antiviral therapy
- Medical subject headings
- Hepatitis C, Chronic, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BetaineDrug
Also called trimethylglycine
Betaine 20 gm/day in 2 divided doses for 48 weeks
Peginterferon alpha 2aDrug
Also called Pegasys
Peginterferon alpha 2a 180mcg/0.5ml by subcutaneous injection weekly for 48 weeks
RibavirinDrug
Also called Copegus
Ribavirin 200mg - weight based, 1000 - 1200 mg/day for body weight < or > 75mg in 2 divided doses
| Study group | Role | What they receive |
|---|---|---|
| Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy | Experimental | The primary objective is to examine safety \& efficacy of betaine when combined with standard anti-viral therapy in previously treated adult subjects with chronic hepatitis C infected with genotype 1. Efficacy will be determined through comparison of the sustained viral response (SVR) to our protocol three-drug regimen (Betaine, Peginterferon plus Ribavirin) to that historically seen in relapsers and non-responders when retreated with standard therapy (Peginterferon and Ribavirin alone).
Betaine (trimethylglycine) dose is 10 gm twice a day for 48 weeks. Pegasys (peginterferon alpha 2a) dose is 180mcg/0.5 ml subcutaneous injection for 48 weeks. Coegus (ribavirin) dose is 200mg - weight based, 1000 - 1200 mg/day for body weight or 75mg in 2 divided doses. Receives: Drug: Betaine; Drug: Peginterferon alpha 2a; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and efficacy of betaine combined with standard antiviral therapy
To examine the safety and efficacy of betaine when combined with standard antiviral therapy in previously treated subjects with chronic hepatitis c genotype 1
Measured: 72 weeks
Secondary outcomes (1)
Effect on interferon gene signaling in peripheral blood mononuclear cells
The effect on interferon gene signaling in peripheral blood mononuclear cells in the first 12 weeks of treatment and 6 months following the end of therapy.
Measured: 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2009 (estimated)
- Study start1 May 2009
- Primary completion12 Jan 2011
- Study completion12 Jan 2011
Why it stopped: new medications with improved response released
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 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
- NCT00882193
- Sponsor's protocol ID
- 0133-09-FB
- Status last verified
- Nov 2023
- First submitted
- 15 Apr 2009
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Therapy Using Betaine in Combination With Peginterferon Alpha-2a Plus Ribavirin in Subjects With Genotype 1 Hepatitis C Who Have Not Achieved a Sustained Viral Response With a Prior Course of Pegylated Interferon and Ribavirin
- ClinicalTrials.gov ID
- NCT00882193
- Acronym / sponsor ID
- 0133-09-FB
- Conditions
- Chronic Hepatitis C, Genotype 1, Relapse
- Keywords
- Chronic hepatitis C, Genotype 1, Nonresponder, Relapser, Betaine, Antiviral therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: new medications with improved response released
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 May 2009 (actual)
- Primary completion
- 12 Jan 2011 (actual)
- Study completion
- 12 Jan 2011 (actual)
- First posted
- 16 Apr 2009 (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.
This is a non-randomized, open-label study examining the safety and efficacy of betaine in addition to standard anti-viral therapy in genotype 1 hepatitis C non-responders or relapsers to previous pegylated interferon plus ribavirin. Betaine (20 gm/day) in 2 divided doses will be added to Peginterferon alpha 2a (180 mcg) plus weight-based Ribavirin (1000 or 1200 mg/day, for body weight < or > 75 kg, respectively, for 48 weeks. Patients must be diagnosed with chronic hepatitis C, genotype I, and have undergone therapy for hepatitis C with pegylated interferon plus ribavirin. Subjects will be followed for safety, tolerability, hepatitis C viral response and the effect on interferon gene signaling in peripheral blood mononuclear cells during therapy.
Detailed description
The primary objective is to examine the safety and efficacy of the betaine when combined with standard anti-viral therapy in previously treated adult subjects with chronic hepatitis C infected with genotype 1. The efficacy will be determined through comparison of the sustained viral response (SVR) to our protocol three-drug regimen (Betaine, Peginterferon plus Ribavirin) to that historically seen in relapsers and non-responders when retreated with standard therapy (Peginterferon and Ribavirin alone).
Secondary objectives include: (1) the comparison of the occurrence of rapid and early virologic response in the first 4 (Rapid Virologic Response, RVR) and 12 (Early Virologic Response, EVR) weeks of therapy, respectively, between the study regimen and historically treated patients. (2) the comparison of ALT normalization between the two groups. and (3) the effect on interferon gene signaling in peripheral blood mononuclear cells (PBMCs) between the two groups in the first 12 weeks of therapy and 6 months following the end of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy | Experimental | Drug: Betaine, Drug: Peginterferon alpha 2a, Drug: RibavirinThe primary objective is to examine safety \& efficacy of betaine when combined with standard anti-viral therapy in previously treated adult subjects with chronic hepatitis C infected with genotype 1. Efficacy will be determined through comparison of the sustained viral response (SVR) to our protocol three-drug regimen (Betaine, Peginterferon plus Ribavirin) to that historically seen in relapsers and non-responders when retreated with standard therapy (Peginterferon and Ribavirin alone). Betaine (trimethylglycine) dose is 10 gm twice a day for 48 weeks. Pegasys (peginterferon alpha 2a) dose is 180mcg/0.5 ml subcutaneous injection for 48 weeks. Coegus (ribavirin) dose is 200mg - weight based, 1000 - 1200 mg/day for body weight or 75mg in 2 divided doses. |
Who may qualify
- Ages
- 19 years and older
- 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, genotype 1, non-responders or relapsers as documented by genotype testing and HCV RNA levels at 12 weeks ( < 2 log change) during therapy or at 3 - 12 months post therapy, respectively.
- Adult subjects 18-70 years of age, of either gender
- Liver biopsy within 3 years prior to the screening 1 visit with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis C.
- 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 (21 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.
- Prior response to therapy and failure to achieve SVR which may have been due to treatment non-compliance, in the assessment of the investigator based upon subject's medical history.
- Participation in any clinical trial of a HCV protease inhibitor of any duration. Subjects may have received other investigational agents for the treatment of HCV, as long as they have also received an adequate course of Peg-IFN/RBV [i.e., the investigational agent could not have replaced either Peg-IFN (such as Albuferon) or RBV (viramidine)].
- History of new hepatitis C exposure within the last 6 months
- Current or intended use of G-CSF and/or GM-CSF during the stud period is prohibited. Current use of erythropoietin (EPO) is prohibited.
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 |
|---|---|---|
| BetaineAlso: trimethylglycineBetaine 20 gm/day in 2 divided doses for 48 weeks | Drug | Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy |
| Peginterferon alpha 2aAlso: PegasysPeginterferon alpha 2a 180mcg/0.5ml by subcutaneous injection weekly for 48 weeks | Drug | Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy |
| RibavirinAlso: CopegusRibavirin 200mg - weight based, 1000 - 1200 mg/day for body weight < or > 75mg in 2 divided doses | Drug | Safety & Efficacy of Betaine Combined with Standard Anti-viral Therapy |
Primary outcome
Safety and efficacy of betaine combined with standard antiviral therapy
Time frame: 72 weeks
To examine the safety and efficacy of betaine when combined with standard antiviral therapy in previously treated subjects with chronic hepatitis c genotype 1
1 secondary outcome
Effect on interferon gene signaling in peripheral blood mononuclear cells
Time frame: 72 weeks
Results and safety
The study was stopped early (reason given: new medications with improved response released). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Betaine, Peginterferon alpha 2a and Ribavirin in people with Chronic Hepatitis C and Genotype 1, run by University of Nebraska at 1 site in United States.
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 21 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: stopped early, as of the sponsor's last update on 30 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: new medications with improved response released). Results are not available in the source record.
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?
Safety and efficacy of betaine combined with standard antiviral 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?
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 30 Nov 2023.