Micro RNA-122 and the Clinical Course of Patients With Chronic Hepatitis C

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
National Science Council, Taiwan
Department of Health, Executive Yuan, R.O.C. (Taiwan)
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00980161
First received: September 16, 2009
Last updated: March 25, 2010
Last verified: March 2010
  Purpose

Combination therapy with peginterferon plus ribavirin has become the current standard of care for chronic hepatitis C (CHC) patients, with an overall sustained virologic response (SVR) rate of 54-63%. Based on the ample evidence, a 48-week course of peginterferon plus weight-based ribavirin therapy is widely recommended to treat HCV genotype 1 infection in different parts of the world. Despite the increased SVR rates with the improved medical therapies, about 25-50% and 10-20% of HCV genotype 1 and HCV genotype 2/3 patients may experience relapse after the cessation of therapy with undetectable HCV viremia at the end of treatment. Moreover, combination therapy is costly and may cause various adverse events. Therefore, individualized therapy based on outcome analysis should be adopted to save medical cost as well as to lessen inadequate treatment. Few studies are aimed to evaluate the host responses of micro RNA regulation during interferon-based therapy and its relationships to the overall treatment responses.

Micro RNA (miRNA) is a single-stand RNA composed of 21-23 nucleotides, which may regulate the function of messenger RNA (mRNA). The regulating mechanisms involving micro RNA between the hosts and the HCV virus include (1) auto-regulation of HCV mRNA by HCV miRNA; (2) regulation of host mRNA by HCV miRNA; and (3) regulation of HCV mRNA by host miRNA. MiR-122 is the abundant liver-specific miRNA which is crucial for efficient HCV replication in culture Huh7 cells stably expressing HCV replicons. Recently, an in vivo study for hepatic miR-122 of 42 patients with CHC who received IFN-based therapy showed that patients who did not respond to IFN therapy had markedly decreased pretreatment miR-122 levels. Although miR-122 is abundant in the liver, liver biopsy is still considered an invasive procedure, which prevents its widespread use in routine clinical practice. The miRNA can be detected in the sera and is stable after 24 hours of room temperature store or repeated freezing and de-freezing. The serum miR-122 levels can reflect the severity of liver injuries in a rat acetaminophen toxicity model. Because miR-122 is liver specific and the miRNA is stable in the sera, the investigators aimed to evaluate the role of serum and hepatic miR-122 on the viral kinetics and the treatment responses and in HCV patients receiving peginterferon and ribavirin combination therapy.


Condition
Hepatitis C

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: The Predictive Role of Serum Micro RNA-122 to the Clinical Course of Chronic Hepatitis C Patients

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Serum micro RNA-122 and sustained virologic response (SVR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Serum and hepatic micro RNA-122


Estimated Enrollment: 200
Study Start Date: September 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
Peg-IFN + RBV with SVR
HCV patients receiving peginterferon alfa-2a and ribavirin with sustained virologic response
Peg-IFN + RBV without SVR
HCV patients receiving peginterferon alfa-2a and ribavirin without sustained virologic response

  Hide Detailed Description

Detailed Description:

Hepatitis C virus (HCV) infection, a leading cause of cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation, affects approximately 170 million individuals worldwide. In Asian-Pacific regions, the prevalence of HCV infection ranges from 0.3-12%, with a geographical variation. Therefore, prevention of HCV transmission and early intervention of HCV infection are urgently needed to reduce or halt the liver-related morbidity and mortality.

Combination therapy with peginterferon plus ribavirin has become the current standard of care for chronic hepatitis C (CHC) patients, with an overall sustained virologic response (SVR) rate of 54-63%. Treatment with weekly peginterferon and weight-based ribavirin for 48 weeks had a significantly higher SVR rate than that for 24 weeks in Caucasian patients with HCV genotype 1 infection (52% to 42%). Based on ample evidence from Western countries, a 48-week course of peginterferon plus weight-based ribavirin therapy is widely recommended to treat HCV genotype 1 infection in different parts of the world. However, recent studies for Asian CHC genotype 1 patients showed favorable treatment response to Caucasian patients with either 24 or 48 weeks of peginterferon plus weight-based ribavirin therapy (50 to 60% for 24 weeks; 75 to 80% for 48 weeks). In contrast, the overall SVR rates were similar across different ethnicity in patients with HCV genotype 2/3 infection.

Despite the increased SVR rates with the improved medical therapies, about 25-50% and 10-20% of HCV genotype 1 and HCV genotype 2/3 patients may experience relapse after the cessation of therapy with undetectable HCV viremia at the end of treatment. Moreover, combination therapy is costly and may cause various adverse events. Therefore, individualized therapy based on outcome analysis should be adopted to save medical cost as well as to lessen inadequate treatment. Currently, HCV viral kinetics is considered to predict treatment response. Patients with rapid virologic response (RVR) are good predictors of SVR; those who fail to achieve RVR but achieve complete or partial early virologic response (cEVR or pEVR) should be put on prolonged therapy; those who fail to achieve EVR should be considered for treatment discontinuation because of low chance for SVR. Various host and viral factors, including race, gender, body weight, baseline viral load, and viral genotype, were considered to predict RVR. However, few studies are aimed to evaluate the host responses of micro RNA regulation during interferon-based therapy and its relationships to the overall treatment responses.

Micro RNA (miRNA) is a single-stand RNA composed of 21-23 nucleotides, which may regulate the function of massager RNA (mRNA). The regulating mechanisms involving micro RNA between the hosts and the HCV virus include (1) auto-regulation of HCV mRNA by HCV miRNA; (2) regulation of host mRNA by HCV miRNA; and (3) regulation of HCV mRNA by host miRNA. MiR-122 is the abundant liver-specific miRNA which is crucial for efficient HCV replication in culture Huh7 cells stably expressing HCV replicons. This observation raised much interest in the role of mir-122 in HCV infection and its potential as a therapeutic target. It was recently reported that the levels of miR-122 and several other miRNAs are regulated by IFN in Huh7 cells and primary mouse hepatocytes and that miRNAs might mediate at least some effects of IFN on HCV RNA replication in vitro. Recently, an in vivo study for hepatic miR-122 of 42 patients with CHC who received IFN-based therapy showed that patients who did not respond to IFN therapy had markedly decreased pretreatment miR-122 levels. Although miR-122 is abundant in the liver, liver biopsy is still considered an invasive procedure, which prevents its widespread use in routine clinical practice. Considering the abundant blood flow through the liver, we speculated that miR-122 can be detected in the sera, and can be used for screening and monitoring the responses by serial blood tests. The miRNA can be detected in the sera and is stable after 24 hours of room temperature store or repeated freezing and de-freezing. In addition, miRNA is resistant to RNase and can be sustained for more than 10 years after adequate freezing. Recent studies have shown the serum miRNA was potentially useful for the detection of cancer and its treatment responses. Furthermore, the serum miR-122 levels can reflect the severity of liver injuries in a rat acetaminophen toxicity model. Because miR-122 is liver specific and the miRNA is stable in the sera, the investigators aimed to evaluate the role of serum and hepatic miR-122 on the viral kinetics and the treatment responses and in HCV patients receiving peginterferon and ribavirin combination therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with chronic hepatitis C receving combination therapy with peginterferon alfa-2a and ribavirin

Criteria

Inclusion Criteria:

  • Treatment naïve
  • Age 18 and older than 18 years old
  • Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months
  • Detectable serum quantitative HCV-RNA (Cobas Taqman v2.0, Roche Diagnostics)
  • Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment
  • A liver biopsy consistent with the diagnosis of chronic hepatitis C
  • Receive 24 or 48 weeks of PEG-IFN alfa plus ribavirin (1,000 mg/day for BW < 75 kg; 1,200 mg/day for BW ≥ 75 kg for HCV genotype 1; 800 mg/day for HCV genotype 2)

Exclusion Criteria:

  • Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
  • Neutropenia (neutrophil count <1,500 per cubic milliliter)
  • Thrombocytopenia (platelet <90,000 per cubic milliliter)
  • Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
  • Mixed HCV genotype 1 with other genotype infection
  • Chronic alcohol abuse (daily consumption > 20 gram per day)
  • Decompensated liver disease (Child-Pugh class B or C)
  • Serum creatinine level more than 1.5 times the upper limit of normal
  • Autoimmune liver disease
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to have contraception
  • Without definite viral information during the study period (sustained viral responders or viral relapsers)
  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: NCT00980161

Contacts
Contact: Chen-Hua Liu, MD 886-2-23123456 ext 63572 jacque_liu@mail2000.com.tw
Contact: Jia-Horng Kao, MD, PhD 886-2-23123456 ext 67307 kaojh@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital, Yun-Lin Branch Recruiting
Douliou, Taiwan
Contact: Shih-Jer Hsu, MD         
Principal Investigator: Shih-Jer Hsu, MD         
Sub-Investigator: Chieh-Chang Chen, MD         
Sub-Investigator: Ming-Lun Han, MD         
Sub-Investigator: Yu-Jen Fang, MD         
Sub-Investigator: Ji-Yuh Lee, MD         
Kinmen Hospital Recruiting
Kimmen, Taiwan
Contact: Tung-Hung Su, MD         
Principal Investigator: Tung-Hung Su, MD         
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 10002
Contact: Chen-Hua Liu, MD         
Principal Investigator: Chen-Hua Liu, MD         
Principal Investigator: Jia-Horng Kao, MD, PhD         
Principal Investigator: Chun-Jen Liu, MD, PhD         
Sub-Investigator: Ming-Yang Lai, MD, PhD         
Sub-Investigator: Pei-Jer Chen, MD, PhD         
Sub-Investigator: Ding-Shinn Chen, MD         
Far Eastern Memorial Hospital Recruiting
Taipei, Taiwan
Contact: Cheng-Chao Liang, MD, BS         
Principal Investigator: Cheng-Chao Liang, MD, BS         
Taipei Municipal Hospital, Ren-Ai Branch Recruiting
Taipei, Taiwan
Contact: Chih-Lin Lin, MD, BS         
Principal Investigator: Chih-Lin Lin, MD, BS         
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Department of Health, Executive Yuan, R.O.C. (Taiwan)
Investigators
Study Chair: Chen-Hua Liu, MD National Taiwan University Hospital
Study Director: Jia-Horng Kao, MD, PhD National Taiwan University Hospital
Principal Investigator: Tung-Hung Su, MD Kimmen Hospital
Principal Investigator: Cheng-Chao Liang, MD, BS Far Estern Menorial Hospital
Principal Investigator: Chih-Lin Lin, MD, BS Taipei Municipal Hospital, Ren-Ai Branch
Principal Investigator: Shih-Jer Hsu, MD National Taiwan University Hospital, Yun-Lin Branch
  More Information

No publications provided

Responsible Party: Chen-Hua Liu, National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00980161     History of Changes
Other Study ID Numbers: 200908039R
Study First Received: September 16, 2009
Last Updated: March 25, 2010
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Hepatitis C
Peginterferon
Ribavirin
MicroRNA

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

ClinicalTrials.gov processed this record on August 28, 2014