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Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00149084
Recruitment Status : Unknown
Verified September 2005 by Hamamatsu University.
Recruitment status was:  Recruiting
First Posted : September 8, 2005
Last Update Posted : September 11, 2006
Yokoyama Foundation for Clinical Pharmacology
Information provided by:
Hamamatsu University

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.

Condition or disease Intervention/treatment Phase
Helicobacter Infections Gastritis Gastric Ulcer Duodenal Ulcer Drug: Lansoprazole, clarithromycin, amoxicillin Phase 3

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 (i.e., 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 (i.e., 30 mg qid in RMs, 15 mg qid in IMs, and 15 mg bid in PMs) for two weeks.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 296 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacogenomics-Based Tailor-Made Strategy for Eradication of Helicobacter Pylori
Study Start Date : April 2003

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Whether the tailored treatment yields a higher eradication rate in comparison with the standard treatment

Secondary Outcome Measures :
  1. Cost-effectiveness of the tailored strategy

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with H. pylori infection

Exclusion Criteria:

  • Patients without H. pylori infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00149084

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Contact: Takahisa Furuta, MD PhD 81-53-435-2850
Contact: Naohito Shirai, MD, PhD

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Hamamatsu University School of Medicine Recruiting
Hamamatsu, Shizuoka, Japan, 431-3192
Contact: Takahisa Furuta, MD, PhD    81-53-435-2850   
Principal Investigator: Takahisa Furuta, MD, PhD         
Sponsors and Collaborators
Hamamatsu University
Yokoyama Foundation for Clinical Pharmacology
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Study Chair: Takahisa Furuta, MD, PhD Center for Clinical Research, Hamamatsu University School of Medicine

Layout table for additonal information Identifier: NCT00149084    
Other Study ID Numbers: Hp.CYP.001
First Posted: September 8, 2005    Key Record Dates
Last Update Posted: September 11, 2006
Last Verified: September 2005
Keywords provided by Hamamatsu University:
The tailored H. pylori eradication therapy
CYP2C19 genotype
23S rRNA
H. pylori infection
Additional relevant MeSH terms:
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Helicobacter Infections
Stomach Ulcer
Duodenal Ulcer
Pathologic Processes
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Peptic Ulcer
Duodenal Diseases
Intestinal Diseases
Gram-Negative Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors