Peripheral Blood Mononuclear Cell (PBMC) Gene Expression in HCV Genotype 1 Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2006 by Kaohsiung Medical University Chung-Ho Memorial Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Kaohsiung Medical University Chung-Ho Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00680173
First received: May 15, 2008
Last updated: February 11, 2010
Last verified: August 2006

May 15, 2008
February 11, 2010
August 2006
April 2009   (final data collection date for primary outcome measure)
Efficacy - Sustained virological response (SVR), HCV RNA seronegative by PCR throughout 24-week off-treatment period. [ Time Frame: 1.5 year ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00680173 on ClinicalTrials.gov Archive Site
  • Rapid virologic response (RVR), HCV RNA seronegative by PCR at week 4. [ Time Frame: 1.5 year ] [ Designated as safety issue: Yes ]
  • Early virological response (EVR), by PCR-negative or at least 2 logs decline from baseline of serum HCV RNA at 12 weeks of treatment. [ Time Frame: 1.5 year ] [ Designated as safety issue: Yes ]
  • Safety - adverse event rate and profile [ Time Frame: 1.5 year ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Peripheral Blood Mononuclear Cell (PBMC) Gene Expression in HCV Genotype 1 Patients
Analysis of Gene Expression of PBMC in the Hepatitis C Virus Genotype 1b-infected Patients During Peg-interferon-α Plus Ribavirin Combination Therapy

Our previous collaborative studies has developed a molecular diagnosis tool, which is characterized with a prediction model consisting single nucleotide polymorphisms (SNPs), for assessing the efficacy of interferon combined therapy for chronic hepatitis C (CHC) patients prior to treatment.

Aims of this project:

  1. To analyze and validate the gene expression profiling dependent of treatment response to peg-interferon-α plus ribavirin combination therapy in CHC genotype-1 patients.
  2. To select the candidate genes and establish a monitoring model assessing the efficacy of interferon treatment.

A combination of pegylated-interferon (PEG-IFN) with ribavirin has been the choice for treating chronic hepatitis C (CHC) patients. In addition to the high cost, the treatment takes 6 to 12 months and often brings significant adverse reactions to some patients. It would therefore be beneficial to include a pre-treatment evaluation and post-treatment monitoring system to maximize the efficacy of CHC therapy. We have established a molecular diagnosis tool for assessing the efficacy of interferon combined therapy for CHC patients prior to treatment. This diagnostic tool is characterized with a prediction model consisting single nucleotide polymorphisms (SNPs) strongly associated with interferon efficacy in treating CHC patients. The prediction model has been validated by hepatitis C samples in Taiwan, and it achieved 80 % accuracy, higher than the current efficacy rates. Supplemented with the viral genotype information would further increase the prediction accuracy to 85%.

In this project, we aim to analyze patients' gene expression profiling during the treatment. The current study will focus on 30 PEG-IFN and ribavirin treated patients with HCV genotype 1 infection. After the responding status of those patients has been confirmed, we will compare gene expression profiling among the different responses before and during treatment. By using this information, we can properly select the candidate genes, and establish a monitoring model with these biomarkers. This monitoring model can thus be applied to assess the efficacy of PEG-IFN plus ribavirin combination treatment.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Chronic Hepatitis C
Drug: pegylated interferon alpha 2a and plus ribavirin
pegylated interferon alpha 2a 180 mcg/week and Ribavirin 1000-1200 mg/day for 24 weeks, follow up for 24 weeks
Other Name: PEGASYS®
  • Active Comparator: A
    15 patients with HCV genotype 1 infection receiving peginterferon plus ribavirin achieve a sustained virological response
    Intervention: Drug: pegylated interferon alpha 2a and plus ribavirin
  • Active Comparator: B
    15 patients with HCV genotype 1 infection receiving peginterferon plus ribavirin did not achieve a sustained virological response
    Intervention: Drug: pegylated interferon alpha 2a and plus ribavirin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
October 2009
April 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male and female patients >18 years of age
  • Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin
  • Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
  • Detectable serum HCV-RNA
  • Liver biopsy findings consistent with the diagnosis of chronic hepatitis C infection with or without compensated cirrhosis (Exception: hemophiliacs in whom biopsy is medically contra-indicated do not require biopsy.)
  • Compensated liver disease (Child-Pugh Grade A clinical classification)
  • Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
  • All fertile males and females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end

Exclusion Criteria:

  • Women with ongoing pregnancy or breast feeding
  • Present therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug
  • Any investigational drug 6 weeks prior to the first dose of study drug
  • Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV)
  • History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
  • Clinical evidence of hepatocellular carcinoma
  • History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
  • Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening
  • Serum creatinine level >1.5 times the upper limit of normal at screening
  • History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
  • History of a severe seizure disorder or current anticonvulsant use
  • History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
  • History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
  • Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
  • Evidence of drug abuse (including excessive alcohol consumption>40 g/day) within one year of study entry
  • Inability or unwillingness to provide informed consent or abide by the requirements of the study
  • Male partners of women who are pregnant
  • Hgb <11 g/dL in women or <12 g/dL in men at screening
  • Any patient with major thalassemia
  • Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
  • Evidence or history of hepatocellular carcinoma
  • Local or Systemic malignancy unstable status
Both
18 Years to 80 Years
No
Contact: Wan-Long Chuang, M.D., Ph.D. 886-7-3121101 ext 7475 waloch@cc.kmu.edu.tw; research.kmuhb@gmail.com
Taiwan
 
NCT00680173
KMUH-IRB- 950419
Yes
Wan-Long Chuang, MD, PhD., Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung Medical University Chung-Ho Memorial Hospital
Not Provided
Principal Investigator: Wan-Long Chuang, MD, PhD Kaohsiung Medical University
Kaohsiung Medical University Chung-Ho Memorial Hospital
August 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP