Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy (sIFN-pred1)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by First Hospital of Jilin University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Chinese Academy of Sciences
Information provided by (Responsible Party):
Junqi Niu, First Hospital of Jilin University
ClinicalTrials.gov Identifier:
NCT01434212
First received: September 8, 2011
Last updated: October 27, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention
Hepatitis
Drug: Interferon Alfa-2b, Ribavirin

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort

Resource links provided by NLM:


Further study details as provided by First Hospital of Jilin University:

Primary Outcome Measures:
  • Blood HCV RNA Copies [ Time Frame: 0h,8h,10h,12h,18h,24h,37h,43h,3d,7d,2w,4w,6w,12w,24w,48w ] [ Designated as safety issue: No ]
    Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.


Secondary Outcome Measures:
  • IL-28B polymorphism [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    IL28 gene polymorphism,rs8099917,rs12979860,etc

  • Microarray Analysis of PBMC Gene Expression [ Time Frame: Baseline,8h,18h,3d ] [ Designated as safety issue: No ]
    During the first 3 days, blood samples are collected for PBMC separation and microarray analysis.

  • HCV genotype [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    HCV NS5A is cloned into T vector and sequenced for evolutionary analysis.

  • Blood Anti-HCV,HBV Antibody [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Co-infection status are analyzed.

  • HCV genome sequencing [ Time Frame: 0h,8h,10h,12h,18h,24h,37h,43h,3d ] [ Designated as safety issue: No ]
    Deep sequencing is used for blood serum HCV genome analysis.

  • Alanine Aminotransferase (ALT) and Aspartate transaminase (AST) [ Time Frame: Baseline,4w,6w,12w,24w,48w ] [ Designated as safety issue: No ]
    ALT AST are assayed to detect the hepatic function.

  • Fibrosis stage [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: No ]
    Fibrosis is analyzed with Fibroscan.

  • Regular blood test [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: Yes ]
    The distribution and absolute count of the different types of blood cells are assayed.

  • Electrocardiography [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: Yes ]
    Electrocardiography is taken to avoid severe side effects.

  • Alcohol ,smoking condition [ Time Frame: Baseline,4w,12w,24w,48w ] [ Designated as safety issue: No ]
    Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.

  • Drug abuse history [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Patients will be asked about their drug usage history.


Biospecimen Retention:   Samples With DNA

Blood serum,Peripheral blood mononuclear cells (PBMC)


Estimated Enrollment: 40
Study Start Date: May 2010
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Interferon and ribavirin
All the patients followed the standard treatment protocol.
Drug: Interferon Alfa-2b, Ribavirin

Interferon:dosage,5 million units/person;frequency,every other day (qod);duration,48 weeks;Subcutaneous injection.

Ribavirin: dosage,15mg/kg/day;frequency,three times a day (t.i.d);duration,48 weeks;take orally.

Other Names:
  • Generic: Recombinant Human Interferon alpha-2b,Ribavirin
  • Brand: Kaiyinyisheng,Weilake
  • FDA Approval number:S20030032,H10940157

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

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  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: NCT01434212

Locations
China, Jilin
First Hospital Jilin University
Changchun, Jilin, China, 130061
Sponsors and Collaborators
First Hospital of Jilin University
Chinese Academy of Sciences
Investigators
Study Chair: Junqi Niu, PhD/MD First Hospital Jilin University
Principal Investigator: Bing Sun, PhD/MD Chinese Academy of Sciences
  More Information

Additional Information:
Publications:

Responsible Party: Junqi Niu, Vice-President of First Hospital of Jilin University, First Hospital of Jilin University
ClinicalTrials.gov Identifier: NCT01434212     History of Changes
Other Study ID Numbers: 2008ZX10004-002-jida01, 2008ZX10002-014-jida01, 2009ZX10004-105-jida01
Study First Received: September 8, 2011
Last Updated: October 27, 2011
Health Authority: China: Ministry of Science and Technology

Keywords provided by First Hospital of Jilin University:
HCV dynamics
Mathematical model
Interferon
Predict
Hepatitis C Virus

Additional relevant MeSH terms:
Hepatitis C
Hepatitis
Hepatitis A
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Liver Diseases
Digestive System Diseases
Enterovirus Infections
Picornaviridae Infections
Ribavirin
Interferons
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014