Ignite Creation Date:
2024-05-05 @ 10:35 PM
Last Modification Date:
2024-10-26 @ 10:21 AM
Study NCT ID:
NCT01141322
Status:
UNKNOWN
Last Update Posted:
2010-06-10
First Post:
2010-01-12
Brief Title:
Cholestatic Drug-induced Liver Injury
Sponsor:
Taipei Veterans General Hospital Taiwan
Organization:
Taipei Veterans General Hospital Taiwan
Study Overview
Official Title:
Cholestatic Drug-induced Liver Injury Correlation With Genotypes of UGT1A1 and 1A7 and Treatment Effect of Ursodeoxycholic Acid
Status:
UNKNOWN
Status Verified Date:
2010-06
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:
DILI
Brief Summary:
Cholestatic drug-induced liver injury DILI is the severe form of DILI with a grave outcome Drug-metabolizing enzymes play an important role in the metabolism of drugs The genetic polymorphism of drug-metabolizing enzymes may influence the activities and expression of these enzymes and thereby affect the susceptibility and severity of DILI UDP-glucuronosyltransferase UGT is an important phase 2 detoxification enzyme which is related to congenital hyperbilirubinemia Recently the genetic polymorphism of UGT1A1 was reported to be associated with jaundice induced by some drugs and UGT1A7 was shown to be related to the susceptibility of hepatocellular carcinoma and other cancers Ursodeoxycholic acid UDCA is a hydrophilic bile acid that is increasingly used for the treatment of various cholestatic disorders The aims of this study are 1 to assess the association of the genetic polymorphism of UGT1A1 and 1A7 and the susceptibility and severity of drug-induced liver injury DILI with emphasis on the cholestatic DILI 2 to evaluate the treatment effect of UDCA in the DILI with special reference to the cholestatic hepatotoxicity
Detailed Description:
Cholestatic drug-induced liver injury DILI is the severe form of DILI with a grave outcome Drug-metabolizing enzymes play an important role in the metabolism of drugs The genetic polymorphism of drug-metabolizing enzymes may influence the activities and expression of these enzymes and thereby affect the susceptibility and severity of DILI UDP-glucuronosyltransferase UGT is an important phase 2 detoxification enzyme which is related to congenital hyperbilirubinemia Recently the genetic polymorphism of UGT1A1 was reported to be associated with jaundice induced by some drugs and UGT1A7 was shown to be related to the susceptibility of hepatocellular carcinoma and other cancers Ursodeoxycholic acid UDCA is a hydrophilic bile acid that is increasingly used for the treatment of various cholestatic disorders The aims of this study are 1 to assess the association of the genetic polymorphism of UGT1A1 and 1A7 and the susceptibility and severity of drug-induced liver injury DILI with emphasis on the cholestatic DILI 2 to evaluate the treatment effect of UDCA in the DILI with special reference to the cholestatic hepatotoxicity
Owing to the limited number of DILI patients 3 years are needed in this study Each year a total of 60 patients with DILI and 60 age- and sex-matched controls will be enrolled in this study Their genetic polymorphisms of UGT1A1 and UGT1A7 will be assessed using the real time PCR or PCR with RFLP The DILI patients will be randomized to UDCA Treatment group and Control group UDCA 13-15 mgkgday with 3 divided doses will be administered to the patients with Treatment group
The frequencies of genotypes of UGT1A1 and 1A7 will be compared between DILI cases and controls survival cases and non-survival cases and cholestatic and non-cholestatic cases Chi-square test with or without Yates correction will be used to compare the categorical parameters A paired t test will be performed to compare the continuous parameters Odds ratios OR and confidence intervals CI will be calculated using a logistic regression analysis The multivariate logistic regression analysis will be applied to check on the OR adjusted with other possible risk factors Survival rates will be estimated from survival curves based on the Kaplan-Meier method and compared with the log-rank test between the UDCA Treatment group and Control group
We believe that this pharmacogenetic study may help us realize the pathogenesis of cholestatic DILI and the clinical trial can elucidate the therapeutic value of UDCA in the DILI especially in the cholestatic hepatotoxicity
Owing to the limited number of DILI patients 3 years are needed in this study Each year a total of 60 patients with DILI and 60 age- and sex-matched controls will be enrolled in this study Their genetic polymorphisms of UGT1A1 and UGT1A7 will be assessed using the real time PCR or PCR with RFLP The DILI patients will be randomized to UDCA Treatment group and Control group UDCA 13-15 mgkgday with 3 divided doses will be administered to the patients with Treatment group
The frequencies of genotypes of UGT1A1 and 1A7 will be compared between DILI cases and controls survival cases and non-survival cases and cholestatic and non-cholestatic cases Chi-square test with or without Yates correction will be used to compare the categorical parameters A paired t test will be performed to compare the continuous parameters Odds ratios OR and confidence intervals CI will be calculated using a logistic regression analysis The multivariate logistic regression analysis will be applied to check on the OR adjusted with other possible risk factors Survival rates will be estimated from survival curves based on the Kaplan-Meier method and compared with the log-rank test between the UDCA Treatment group and Control group
We believe that this pharmacogenetic study may help us realize the pathogenesis of cholestatic DILI and the clinical trial can elucidate the therapeutic value of UDCA in the DILI especially in the cholestatic hepatotoxicity
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