Ignite Creation Date:
2024-05-05 @ 9:54 PM
Last Modification Date:
2024-10-26 @ 10:10 AM
Study NCT ID:
NCT00980161
Status:
UNKNOWN
Last Update Posted:
2010-03-26
First Post:
2009-09-16
Brief Title:
Micro RNA-122 and the Clinical Course of Patients With Chronic Hepatitis C
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
The Predictive Role of Serum Micro RNA-122 to the Clinical Course of Chronic Hepatitis C Patients
Status:
UNKNOWN
Status Verified Date:
2010-03
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 23 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
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
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 03-12 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 23 infection
Despite the increased SVR rates with the improved medical therapies about 25-50 and 10-20 of HCV genotype 1 and HCV genotype 23 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
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 23 infection
Despite the increased SVR rates with the improved medical therapies about 25-50 and 10-20 of HCV genotype 1 and HCV genotype 23 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None