Hepatitis CPhase 2/3NCT00310336
Chronic Hepatitis C Non-Responder Study With AdoMet and Betaine
A Phase 2/3 study testing S-adenosyl-L-methionine, betaine and pegylated interferon alpha2b in people with Hepatitis C, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
50-60% of patients with chronic hepatitis C are not cured by treatment with pegylated IFNα plus ribavirin. Retreatment of non-responders of previous (pegylated) IFNα plus ribavirin therapies with pegylated IFNα plus ribavirin results in a sustained response in less than 10% of the patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- S-adenosyl-L-methionine, betaine and pegylated interferon alpha2b
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Aug 2006to Sep 2009
- Phase
- Phase 2/3
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female between 18 and 65 years.
- Non-responders in previous treatments with IFNα plus ribavirin or pegylated IFNα plus ribavirin.
- Elevated ALT-levels on at least two occasions during >6 months preceding entry.
- Detection of HCV RNA in serum (PCR).
- Compensated liver disease (Child-Pugh A) and a Child-Pugh score <5.
- The following minimal hematologic and biochemical criteria:
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- Hemoglobin for males and females >11g/dl
- Absolute Neutrophil count >1500 cells/mm3
- Platelets >75'000/mm3
- HBs Ag negative.
- ANA <1:320, and no evidence for autoimmune hepatitis.
- α-Fetoprotein <50μg/l (when between upper limit of normal and 50μg/l, ultrasonographical exclusion of hepatocellular carcinoma (HCC) is needed).
- Fasting blood glucose within normal limits, if history of diabetes or hypertension, a pre-therapy ocular examination is indicated.
- TSH within normal limits or adequately controlled.
- Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 2-3 week period prior to the first dose of study drug. Additionally, all fertile males and females must be using effective contraception during treatment and during the 6 months after treatment end. This may include, but is not limited to, using birth control pills, IUDs, condoms, diaphragms, or implants, being surgically sterilized, or being in a post-menopausal state.
- Willingness to give written informed consent and willingness to participate to and comply with the study
Who cannot join
- Women with ongoing pregnancy or breast feeding.
- Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBe Ag.
- Positive test at screening for HIV.
- History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
- Hypersensitivity to study drugs.
- Participation in any other clinical trial within 30 days of entry into this protocol.
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- Treatment with any investigational drug within 30 days of entry into this protocol.
- History or evidence of decompensated liver disease (Child-Pugh B/C) and a Child-Pugh score >5. Ascites, coagulopathy, hyperbilirubinemia, hepatic encephalopathy, or hypoalbuminemia and a Child-Pugh score >5 are conditions consistent with decompensated liver disease.
- History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease.
- Hepatocellular carcinoma (HCC) or α-Fetoprotein >50μg/l.
- Patients with organ transplants other than cornea and hair transplant.
- Therapy with any antisystemic or immunomodulatory treatment (including supra-physiologic doses of steroids or radiation) <6 months prior the first dose of study drug
- Hemoglobinopathy (e.g. thalassemia) or any other cause of or tendency for hemolysis.
- Any known preexisting medical condition that could interfere with the patient's participation in and completion of the study such as:
- Preexisting psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychosis, suicidal ideation and/or suicidal attempts (based on a mandatory psychiatric advice).
- CNS trauma or active seizure disorders requiring medication.
- Significant cardiovascular dysfunction.
- Poorly controlled diabetes mellitus.
- Renal dysfunction, i.e. serum creatinine levels >1.5 times upper limit of normal.
- Autoimmune diseases.
- Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration).
- Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids.
- Clinical gout.
- Important substance abuse (alcohol >80 g/d, i.v. drugs etc.).
- Active opportunistic infections.
- Non-Hodgkin lymphoma or Hodgkin lymphoma.
- Kaposi sarcoma.
- Inability or unwillingness to provide informed consent or abide by the requirements of the study.
- Male partners of pregnant women.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel
Basel, Canton of Basel-City, 4031
About this study
Official title: Chronic Hepatitis C: Treatment of (Peg)Interferon Alpha - Ribavirin Non-Responders With Pegylated Interferon alpha2b, Ribavirin, AdoMet and Betaine
50-60% of patients with chronic hepatitis C are not cured by treatment with pegylated IFNα plus ribavirin.
Retreatment of non-responders of previous (pegylated) IFNα plus ribavirin therapies with pegylated IFNα plus ribavirin results in a sustained response in less than 10% of the patients.
Read more
Extensive analysis of IFNα signaling in cells expressing HCV proteins, in transgenic mice expressing HCV proteins, and in liver biopsies from patients with chronic hepatitis C point to STAT1 methylation as an important posttranslational modification targeted by HCV to inhibit IFNα signaling.
STAT1 methylation can be increased and IFNα can be improved by adding AdoMet and betaine.
The study is designed to test the hypothesis that a combination treatment with pegylated IFNα2b, ribavirin, AdoMet and betaine is superior to the current standard combination therapy with pegylated IFNα plus ribavirin.
- Conditions
- Hepatitis C
- Being tested
- S-adenosyl-L-methionine, betaine, pegylated interferon alpha2b, ribavirin
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-adenosyl-L-methionineDrug
betaineDrug
pegylated interferon alpha2bDrug
ribavirinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained response rate
Secondary outcomes (1)
Early virologic response after 12 weeks of therapy with PegIntron, Rebetol, AdoMet and betaine.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2006 (estimated)
- Study startAug 2006
- Primary completionAug 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Investigators
- Markus H Heim, MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00310336
- Sponsor's protocol ID
- EKBB 37/06
- Status last verified
- Oct 2010
- First submitted
- 31 Mar 2006
- Last updated
- 28 Oct 2010
- Results posted
- No
Publications
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.
PubMed 16557551Duong FH, Christen V, Berke JM, Penna SH, Moradpour D, Heim MH. Upregulation of protein phosphatase 2Ac by hepatitis C virus modulates NS3 helicase activity through inhibition of protein arginine methyltransferase 1. J Virol. 2005 Dec;79(24):15342-50. doi: 10.1128/JVI.79.24.15342-15350.2005.
PubMed 16306605Duong FH, Filipowicz M, Tripodi M, La Monica N, Heim MH. Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology. 2004 Jan;126(1):263-77. doi: 10.1053/j.gastro.2003.10.076.
PubMed 14699505Blindenbacher A, Duong FH, Hunziker L, Stutvoet ST, Wang X, Terracciano L, Moradpour D, Blum HE, Alonzi T, Tripodi M, La Monica N, Heim MH. Expression of hepatitis c virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. Gastroenterology. 2003 May;124(5):1465-75. doi: 10.1016/s0016-5085(03)00290-7.
PubMed 12730885Heim MH, Moradpour D, Blum HE. Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway. J Virol. 1999 Oct;73(10):8469-75. doi: 10.1128/JVI.73.10.8469-8475.1999.
PubMed 10482599Filipowicz M, Bernsmeier C, Terracciano L, Duong FH, Heim MH. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One. 2010 Nov 8;5(11):e15492. doi: 10.1371/journal.pone.0015492.
PubMed 21079746
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic Hepatitis C: Treatment of (Peg)Interferon Alpha - Ribavirin Non-Responders With Pegylated Interferon alpha2b, Ribavirin, AdoMet and Betaine
- ClinicalTrials.gov ID
- NCT00310336
- Acronym / sponsor ID
- EKBB 37/06
- Conditions
- Hepatitis C
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Aug 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 3 Apr 2006 (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.
50-60% of patients with chronic hepatitis C are not cured by treatment with pegylated IFNα plus ribavirin.
Retreatment of non-responders of previous (pegylated) IFNα plus ribavirin therapies with pegylated IFNα plus ribavirin results in a sustained response in less than 10% of the patients.
Extensive analysis of IFNα signaling in cells expressing HCV proteins, in transgenic mice expressing HCV proteins, and in liver biopsies from patients with chronic hepatitis C point to STAT1 methylation as an important posttranslational modification targeted by HCV to inhibit IFNα signaling.
STAT1 methylation can be increased and IFNα can be improved by adding AdoMet and betaine.
The study is designed to test the hypothesis that a combination treatment with pegylated IFNα2b, ribavirin, AdoMet and betaine is superior to the current standard combination therapy with pegylated IFNα plus ribavirin.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male and female between 18 and 65 years.
- Non-responders in previous treatments with IFNα plus ribavirin or pegylated IFNα plus ribavirin.
- Elevated ALT-levels on at least two occasions during >6 months preceding entry.
- Detection of HCV RNA in serum (PCR).
- Compensated liver disease (Child-Pugh A) and a Child-Pugh score <5.
Key exclusion criteria (29 listed)
- Women with ongoing pregnancy or breast feeding.
- Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBe Ag.
- Positive test at screening for HIV.
- History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures).
- Hypersensitivity to study drugs.
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 |
|---|---|---|
| S-adenosyl-L-methionine | Drug | – |
| betaine | Drug | – |
| pegylated interferon alpha2b | Drug | – |
| ribavirin | Drug | – |
Primary outcome
Sustained response rate
1 secondary outcome
Early virologic response after 12 weeks of therapy with PegIntron, Rebetol, AdoMet and betaine.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2010.
- 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.
- Background: PubMed 16306605Duong FH, Christen V, Berke JM, Penna SH, Moradpour D, Heim MH. Upregulation of protein phosphatase 2Ac by hepatitis C virus modulates NS3 helicase activity through inhibition of protein arginine methyltransferase 1. J Virol. 2005 Dec;79(24):15342-50. doi: 10.1128/JVI.79.24.15342-15350.2005.
- Background: PubMed 14699505Duong FH, Filipowicz M, Tripodi M, La Monica N, Heim MH. Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology. 2004 Jan;126(1):263-77. doi: 10.1053/j.gastro.2003.10.076.
- Background: PubMed 12730885Blindenbacher A, Duong FH, Hunziker L, Stutvoet ST, Wang X, Terracciano L, Moradpour D, Blum HE, Alonzi T, Tripodi M, La Monica N, Heim MH. Expression of hepatitis c virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. Gastroenterology. 2003 May;124(5):1465-75. doi: 10.1016/s0016-5085(03)00290-7.
- Background: PubMed 10482599Heim MH, Moradpour D, Blum HE. Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway. J Virol. 1999 Oct;73(10):8469-75. doi: 10.1128/JVI.73.10.8469-8475.1999.
- Derived from this study: PubMed 21079746Filipowicz M, Bernsmeier C, Terracciano L, Duong FH, Heim MH. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One. 2010 Nov 8;5(11):e15492. doi: 10.1371/journal.pone.0015492.
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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.
Markus H Heim, MD principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing S-adenosyl-L-methionine, betaine and pegylated interferon alpha2b in people with Hepatitis C, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 16 inclusion and 29 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: finished, as of the sponsor's last update on 28 Oct 2010. 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 Switzerland. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 response rate. 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 NCT00310336, which also lists 6 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 28 Oct 2010.