Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00149084
Status:
UNKNOWN
Last Update Posted:
2006-09-11
First Post:
2005-09-06
Brief Title:
Tailored Treatment of H Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H Pylori
Sponsor:
Hamamatsu University
Organization:
Hamamatsu University
Study Overview
Official Title:
Pharmacogenomics-Based Tailor-Made Strategy for Eradication of Helicobacter Pylori
Status:
UNKNOWN
Status Verified Date:
2005-09
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:
The eradication rate of the standard H pylori eradication therapy such as the triple therapy with a proton pump inhibitor PPI amoxicillin and clarithromycin depends on bacterial susceptibility to clarithromycin and genotypes of CYP2C19 in patients The investigators intend to investigate whether the tailored therapy based on the two above-mentioned factors increases the cure rate of the initial eradication therapy
Detailed Description:
Current treatment strategies for the eradication of H pylori include a proton pump inhibitor PPI and one or two anti-bacterial agents such as amoxicillin clarithromycin and metronidazole
PPIs such as lansoprazole and omeprazole are mainly metabolized in the liver by a genetically determined enzyme S-mephenytoin 4-hydroxylase CYP2C19 Plasma concentrations of PPIs and their activity for acid inhibition depend to a significant extent on the genetic differences in the activity of this enzyme The acid inhibition attained by the standard dose of a PPI is sometimes therapeutically insufficient in individuals with the rapid extensive metabolizer RM genotype of CYP2C19 whereas that in individuals with poor metabolizer PM genotype of CYP2C19 is in most cases clinically sufficient We have reported that the CYP2C19 genotype status is one of the determinants of H pylori eradication therapy In the triple therapy with a PPI amoxicillin and clarithromycin bacterial susceptibility to clarithromycin as well as the CYP2C19 genotype status was significantly related to eradication rates of H pylori Therefore the tailored treatment based on these two factors is expected to increase the eradication rates of the initial therapy
Interestingly both of CYP2C19 genotypes and bacterial susceptibility to clarithromycin can be measured by the genetic test of the single nucleotide polymorphisms SNPs of the CYP2C19 gene and the 23S rRNA gene of H pylori respectively We have recently developed the inexpensive and reliable high-throughput method for measurement of such SNPs by the invader assay Polymorphisms of CYP2C19 of patients and mutations of 23S rRNA of H pylori associated with susceptibility to clarithromycin can be detected from the gastric tissue samples infected with H pylori such as the gastric tissue sample already used for rapid urease test RUT
Then we treat H pylori-positive patients by the tailored regimen based on genotypes of CYP2C19 of patients and 23S rRNA of H pylori or the standard regimen and test the therapeutic efficacy of this pharmacogenomics-based tailored strategy in a prospective manner
Patients were randomly assigned to the standard or tailored regimen group with the use of a computer-generated randomization list based on a blocked randomization method
Patients assigned to the standard regimen group were treated with 30 mg of lansoprazole bid 400 mg of clarithromycin bid and 750 mg of amoxicillin bid for one week which had been approved under the Japanese formulary regulation regardless of any pharmacogenomic backgrounds of H pylori-infected peptic ulcer patients
In the tailored regimen group patients infected with a clarithromycin-sensitive strain of H pylori are treated with triple therapy consisting of clarithromycin 200 mg tid amoxicillin 500 mg tid and the individualized doses of lansoprazole dose ie 30 mg tid in RMs 15 mg tid in IMs and 15 mg bid in PMs for one week while patients infected with a clarithromycin-resistant strain of H pylori are treated with dual therapy consisting of amoxicillin 500 mg qid and the individualzed dose of lansoprazole ie 30 mg qid in RMs 15 mg qid in IMs and 15 mg bid in PMs for two weeks
PPIs such as lansoprazole and omeprazole are mainly metabolized in the liver by a genetically determined enzyme S-mephenytoin 4-hydroxylase CYP2C19 Plasma concentrations of PPIs and their activity for acid inhibition depend to a significant extent on the genetic differences in the activity of this enzyme The acid inhibition attained by the standard dose of a PPI is sometimes therapeutically insufficient in individuals with the rapid extensive metabolizer RM genotype of CYP2C19 whereas that in individuals with poor metabolizer PM genotype of CYP2C19 is in most cases clinically sufficient We have reported that the CYP2C19 genotype status is one of the determinants of H pylori eradication therapy In the triple therapy with a PPI amoxicillin and clarithromycin bacterial susceptibility to clarithromycin as well as the CYP2C19 genotype status was significantly related to eradication rates of H pylori Therefore the tailored treatment based on these two factors is expected to increase the eradication rates of the initial therapy
Interestingly both of CYP2C19 genotypes and bacterial susceptibility to clarithromycin can be measured by the genetic test of the single nucleotide polymorphisms SNPs of the CYP2C19 gene and the 23S rRNA gene of H pylori respectively We have recently developed the inexpensive and reliable high-throughput method for measurement of such SNPs by the invader assay Polymorphisms of CYP2C19 of patients and mutations of 23S rRNA of H pylori associated with susceptibility to clarithromycin can be detected from the gastric tissue samples infected with H pylori such as the gastric tissue sample already used for rapid urease test RUT
Then we treat H pylori-positive patients by the tailored regimen based on genotypes of CYP2C19 of patients and 23S rRNA of H pylori or the standard regimen and test the therapeutic efficacy of this pharmacogenomics-based tailored strategy in a prospective manner
Patients were randomly assigned to the standard or tailored regimen group with the use of a computer-generated randomization list based on a blocked randomization method
Patients assigned to the standard regimen group were treated with 30 mg of lansoprazole bid 400 mg of clarithromycin bid and 750 mg of amoxicillin bid for one week which had been approved under the Japanese formulary regulation regardless of any pharmacogenomic backgrounds of H pylori-infected peptic ulcer patients
In the tailored regimen group patients infected with a clarithromycin-sensitive strain of H pylori are treated with triple therapy consisting of clarithromycin 200 mg tid amoxicillin 500 mg tid and the individualized doses of lansoprazole dose ie 30 mg tid in RMs 15 mg tid in IMs and 15 mg bid in PMs for one week while patients infected with a clarithromycin-resistant strain of H pylori are treated with dual therapy consisting of amoxicillin 500 mg qid and the individualzed dose of lansoprazole ie 30 mg qid in RMs 15 mg qid in IMs and 15 mg bid in PMs for two weeks
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