Chronic Hepatitis C Non-Responder Study With AdoMet and Betaine

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00310336
First received: March 31, 2006
Last updated: October 27, 2010
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: S-adenosyl-L-methionine
Drug: betaine
Drug: pegylated interferon alpha2b
Drug: ribavirin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chronic Hepatitis C: Treatment of (Peg)Interferon Alpha - Ribavirin Non-Responders With Pegylated Interferon alpha2b, Ribavirin, AdoMet and Betaine

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Sustained response rate

Secondary Outcome Measures:
  • Early virologic response after 12 weeks of therapy with PegIntron, Rebetol, AdoMet and betaine.

Estimated Enrollment: 30
Study Start Date: August 2006
Study Completion Date: September 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:
  • 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

Exclusion Criteria:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310336

Locations
Switzerland
University Hospital Basel
Basel, BS, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Markus H Heim, MD University Hospital, Basel, Switzerland
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00310336     History of Changes
Other Study ID Numbers: EKBB 37/06
Study First Received: March 31, 2006
Last Updated: October 27, 2010
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Betaine
Ribavirin
Interferon-alpha
Interferons
Peginterferon alfa-2b
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 11, 2014