Clinical trial NCT01434212: Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy
Official title: Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis
Keywords: HCV dynamics
Mathematical model
Interferon
Predict
Hepatitis C Virus
Lead sponsor: The First Hospital of Jilin University
Sponsor class: OTHER
Collaborators: name: Chinese Academy of Sciences
First posted: 2011-09-14
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients are from the northeast of China. Most of the patients have been infected by the hepatitis c virus due to the drug abuse. Many of them share the same syringe for drug intravenous injection. However, HIV infection has been rarely detected.

Brief summary: The purpose of this study is to determine whether the outcome of interferon therapy on HCV infected patients can be early precisely predicted with a novel mathematic method with Chinese population.

Detailed description: Hepatitis C virus (HCV) infection rate in China is about 3%, which means about 30 million patients. Combination therapy of ribavirin and interferons (IFN) is the standard clinical treatment of HCV chronical infections. However, overall rate of sustained virological response (SVR) still do not exceed 60% even with ribavirin and peg-IFN. Due to several virus- and patient-related factors, treatment is even less successful in certain populations, especially in HCV genotype 1 infection. Thus the standard therapy duration is optimized according to the virus genotype in the clinical practice. Nowadays, two direct antiviral agents (DAAs) have been approved by Food and Drug Administration (FDA) of USA this year, which increases the SVR rate. However, high price, side effects and long duration render people to hesitate about the addition of the third drug in the traditional prescription.

Predicting the outcome of traditional therapy is the cornerstone of the personalized therapy for HCV infected patients. In order to obtain an accurate prediction, different methods have been tried. Several indicators have been suggested to predict the final treatment outcomes. Rapid Virus Response (RVR), which indicates the non-detectable virus at the forth week since therapy starts, has been used to predict the final treatment outcome.Other indicators, including virus genotype, host genotype of IL-28B, human race and interferon stimulated genes (ISG) expression have also been shown to relate to and be able to predict the treatment outcomes to some extent. Here the investigators propose that the HCV virus dynamics analysis will give a more precise prediction for the therapy outcome.

The general idea is that blood HCV titration data is obtained continuously in the early treatment period (first 6 weeks) of the patients who have strictly followed the therapy method. These titration data will be used to draw virus dynamics curve and calculate the corresponding parameters individually. The parameter(s) that can distinguish patients who reach the therapy evaluation standard from those who failed to reach the evaluation standard will be selected out, and such parameter(s) may be used to predict the therapy outcome of a new patient in the early stage of his/her treatment.

Eligibility criteria: Inclusion Criteria:

* Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
* Serum HCV-RNA \> 3 log IU/ml
* Has been infected by HCV for more than 6 months
* ALT,AST have been elevated continuously, inflammation and necrosis have been observed according to the histology diagnosis (G\>=2),modest liver fibrosis (S\>=2)
* For those patients whose ALT are normal,treatment accord to the liver biopsy. If obvious fibrosis has been detected (S2,S3),treatment should be done.For those S0,S1 stage patients, treatment could be delayed, but ALT/AST should be assayed every 3-6 months.
* Compensated liver disease
* Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin

Exclusion Criteria:

History:

* Has history of decompensated liver diseases
* Has been treated with other anti-virus drugs,or anti-tumor drugs,immuno-suppression drugs
* Has a history of autoimmune hepatitis
* History of a severe seizure disorder or current anticonvulsant use
* History or other evidence of a medical condition associated with chronic liver disease other than HCV which would make the patient, in the opinion of the investigator, unsuitable for the study (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
* 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 4g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
* 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

Current condition:

* Pregnant women or women during the lactation period
* Co-infected with hepatitis b virus or human immunodeficiency virus
* Liver cancer or alpha-fetoprotein \> 100ng/ml
* Blood neutrophils count \< 1500/mm3, or platelets count \< 90000/mm3
* Female hemoglobin \<11.5g/dL, male hemoglobin \<12.5g/dL
* Blood creatinine \> 1.5 ULN
* Have severe mental diseases,especially depression
* Severe pulmonary dysfunction
* Severe cardiovascular disease
* Uncontrolled diabetes
* Uncontrolled thalassemia
* Evidence of alcohol abuse (alcohol consumption\>40 g/day)
* Unwillingness to provide informed consent or abide by the requirements of the study
* Local or System malignancy unstable status

Primary outcomes:
measure: Blood HCV RNA Copies
timeFrame: 0h,8h,10h,12h,18h,24h,37h,43h,3d,7d,2w,4w,6w,12w,24w,48w
Secondary outcomes:
measure: IL-28B polymorphism
timeFrame: Baseline
measure: Microarray Analysis of PBMC Gene Expression
timeFrame: Baseline,8h,18h,3d
measure: HCV genotype
timeFrame: Baseline
measure: Blood Anti-HCV,HBV Antibody
timeFrame: Baseline
measure: HCV genome sequencing
timeFrame: 0h,8h,10h,12h,18h,24h,37h,43h,3d
measure: Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)
timeFrame: Baseline,4w,6w,12w,24w,48w
measure: Fibrosis stage
timeFrame: Baseline,4w,12w,24w,48w
measure: Regular blood test
timeFrame: Baseline,4w,12w,24w,48w
measure: Electrocardiography
timeFrame: Baseline,4w,12w,24w,48w
measure: Alcohol ,smoking condition
timeFrame: Baseline,4w,12w,24w,48w
measure: Drug abuse history
timeFrame: Baseline
Other outcomes:
Locations:
city: Changchun
country: China
facility: First Hospital Jilin University
state: Jilin
Study officials:
affiliation: First Hospital Jilin University
name: Junqi Niu, PhD/MD
role: STUDY_CHAIR
affiliation: Chinese Academy of Sciences
name: Bing Sun, PhD/MD
role: PRINCIPAL_INVESTIGATOR
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