Effects of H.Pylori Eradication on Microbiome

August 20, 2018 updated by: University of Latvia

Long Term Effects of H.Pylori Eradication on Microbiome and Adverse Events

The aim of this Project is, within the scope of industrial research, to evaluate the long term effects of H.pylori eradication on microbiome (gut microbiome, upper respiratory tract microbiome) and lasting adverse events. In addition, the project aims to evaluate its effects on abundance and prevalence of extended-spectrum beta-lactamases coding genes and develop cost effective ESBL screening test prototype.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

The current international guidelines and expert working groups are encouraging "search-and-treat" strategy for H.pylori to prevent gastric cancer1, 2. The highest yield of this approach is expected in countries with high incidence of gastric cancer and high prevalence of H.pylori infection. This approach will be further supported by the Maastricht V European guidelines (manuscript in preparation). The rationale for this approach is that 1-2% of the infected individuals are developing gastric cancer; the International Agency for Research on Cancer has classified H.pylori infection as Class I carcinogen3, 4. A study in Matsu island with high gastric cancer risk has suggested that gastric cancer incidence can be decreased by 25% by such strategy5; the limitations, however, include lack of the control group.

Three recent meta-analysis have confirmed the cost-effectiveness of such approach6-8; of course, those are based on the limited currently available data on potential risks caused by population-based strategy application.

In the countries which are expected to benefit from the strategy most this would mean offering eradication treatment to the majority of population, e.g. in Latvia this would require antibiotic treatment to 79% of population9, and would change the current status of low antibiotic consumption country to an average consumption country. This could potentially result in adverse consequences unrelated to H.pylori.

In a country with low H.pylori resistance to clarithromycin (such as Latvia), the recommended H.pylori 1st-line standard eradication regimen would consist of clarithromycin in combination to either amoxicillin or metronidazole, and a proton-pump inhibitor; the duration would be at least 10 days10. Areas with higher H.pylori resistance to clarithromycin would require more aggressive treatment modalities, e.g. by including levofloxacin to the regimen. The potential adverse events caused by such therapies to microbiome are insufficiently studied; the expert opinion that are developing guidelines is generally limited to the consideration that 1-2 week single-time antibiotic treatment would be a minor and fully reversible intervention upon microbiome since according to the available statistic in many countries the average antibiotic intake rates one or several treatments per year in a subject.

However, from the limited data available, there is a clear message that even one-week treatment with macrolides (clarithromycin, azithromycin) is increasing the resistance of macrolide-resistant S.pneumoniae in pharynx in healthy volunteers; this difference was statistically significant within a period of 180 days11.

Thus the aim of this project proposal is to evaluate the long term effects of H.pylori eradication on Gastro intestinal tract (GIT) microbiome, evaluate its effects on abundance and prevalence of extended-spectrum beta-lactamases (ESBL) coding genes and develop cost effective ESBL screening test prototype. To reach this goal during within the scope of this project fecal samples will be collected of patients that are undergoing the eradication therapy at two time points: before the start eradication and one year after the final treatment. In order to decrease the number of feces samples that patients shall have to acquire and standardize the sampling procedure, participants should explore the possibility to employ fecal occult blood test containers. Since there are no conclusively positive reports on employment of these devices in such analyses within the scope of this research participants shall also develop an appropriate DNA extraction methodology. Further, employing Next generation sequencing based analyses participants shall determine the microbial community composition within each sample and through comparison of data from each time point participants should be able to estimate the long term effects of eradication therapy. Following this analysis participants should perform the identification of ESBL repertoire within each sample and also evaluation their abundances abundance. Similarly as in the case of community analysis the comparison of both time points shall allow to estimate the effects of eradication therapy. Following the acquisition of the data participants shall outsource the creation of ESBL screening test prototype, which shall be based on employment micro-bead technology.

Study Type

Interventional

Enrollment (Anticipated)

900

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Latvia
      • Riga, Latvia, LV 1586
        • University of Latvia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Individuals with established H.pylori infection
  • Individuals in whom H.pylori eradication therapy is indicated according to the international or national recommendations
  • Individuals who agree to undergo H.pylori eradication therapy

Exclusion Criteria:

  • Severely sick patients
  • Individuals in whom H.pylori eradication therapy is contra-indicated due to any reasons
  • Individuals unable or unwilling to provide a sample for microbiome testing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: H.pylori Eradication index
Microbiome diversity detection in Participants Positive for H.pylori and undergoing Eradication therapy with Clarythromycin-containing eradication therapy
Other: Microbiome Diversity detection
detection of microbiome composition and detection of specific mutations in genes conferring resistance to antibiotics
No Intervention: Control
Microbiome diversity detection in Participants Without H.pylori Eradication therapy
Active Comparator: H.pylori Eradication comparative
Microbiome diversity detection in Participants Positive for H.pylori and undergoing Eradication therapy with high dose Amoxicillin and bismuth containing eradication therapy
Other: Microbiome Diversity detection
detection of microbiome composition and detection of specific mutations in genes conferring resistance to antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of various H.pylori eradication regimens upon the gut microbiome
Time Frame: 6-36 months between the initial and the follow-up sample
Gut microbiome
6-36 months between the initial and the follow-up sample

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of various H.pylori eradication regimens upon adverse events in short term
Time Frame: 21-28 days following the expected starting data of the treatmennt
Telephone interview following eradication
21-28 days following the expected starting data of the treatmennt
Effectiveness of various H.pylori eradication regimens
Time Frame: 1-12 months following eradication therapy
Effectiveness of H.pylori eradication will be evaluated by 13C urea breath test (UBT). Initially, 14 day clarythromycin-containing triple therapy will be compared to 14-day amoxicillin and bismuth containing therapy
1-12 months following eradication therapy
Effects of various H.pylori eradication regimens upon the pharyngeal microbiome
Time Frame: 6-36 months between the initial and the follow-up sample
Pharyngeal microbiome before and after H.pylori eradication will be compared
6-36 months between the initial and the follow-up sample
Effects of various H.pylori eradication regimens upon long-lasting adverse events
Time Frame: 6 months - 10 years following eradication
Adverse evens like symptoms of gastro-esophageal reflux disease, obesity, functional bowel disease will be addressed
6 months - 10 years following eradication

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Latvia

Collaborators

Latvian Biomedical Research and Study Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 29, 2017

Primary Completion (Anticipated)

October 29, 2019

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

July 21, 2017

First Submitted That Met QC Criteria

July 26, 2017

First Posted (Actual)

July 27, 2017

Study Record Updates

Last Update Posted (Actual)

August 22, 2018

Last Update Submitted That Met QC Criteria

August 20, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 1.1.1.1/16/A/272

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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