Study on the Probiotics Regulating miRNA in H. Pylori-induced Wnt/β-catenin Gastric Carcinogenesis.

March 20, 2024 updated by: Yao-Jong Yang, National Cheng-Kung University Hospital

Background. H. pylori has recognized as a type 1 carcinogen for gastric adenocarcinoma. Although H. pylori eradication promises to reduce the risk of gastric cancer, the regression rate of intestinal metaplasia (IM) after eradication is unsatisfactory. Therefore, to find the mechanism of IM persistent and a new strategy to improve IM regression are critical for reducing gastric cancer development. The canonical Wnt/beta-catenin signaling pathway upregulating cyclooxygenase-2 (COX-2) transcriptional activity involves gastric carcinogenesis after H. pylori infection. Investigators have established an in vitro model that H. pylori induces a cagA-dependent nuclear COX-2 expression in both GES-1 and AGS cells. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs and have been shown to involve in the gastric carcinogenesis. Among these gastric cancer-related miRNA candidates, some were reported to interact with Wnt/β-catenin pathway. Clinically, H. pylori eradication plus celecoxib therapy results in about one-third cases being IM regression, which correlated to the nuclear β-catenin and COX-2 expression before treatment. Based on the probiotics ingestion can ameliorate H. pylori-induced inflammatory pathways, investigators hypothesis that H. pylori eradication with probiotics supplement may promote IM regression through regulating certain miRNAs and Wnt/β-catenin signaling. The aims of this 3-year grant will

  1. to establish the H. pylori induces the Wnt/beta-catenin and COX-2 signaling pathway in vitro.
  2. to investigate the effects and mechanisms of L. acidophilus and B. latis on H. pylori-induced Wnt/beta-catenin oncogenesis pathway.
  3. to study whether probiotics ingestion promote IM regression or ameliorate IM progression in H. pylori-infected patients after successful eradication therapy.

Materials and Methods. A H. pylori (HP238) isolate strain, GES-1, and AGS cells will be used for in vitro study. The protein levels of cell tests will measured by western blot. The differences of miRNAs expression between monk, cells infected with H. pylori, and cells pretreated with probiotics than infected by H. pylori will be analyzed by next generation sequencing method. H. pylori-infected patients with IM will be randomly allocated to receive probiotics or controls, the 2nd endoscopy will be arranged at the 12th month to evaluate the IM status.

Anticipated results. This study will to establish the H. pylori-induced Wnt/beta-catenin oncogenesis pathway in vitro. Furthermore, the effect and mechanism of probiotics inhibit the H. pylori-induced Wnt/beta-catenin signaling will be clarified. Finally, investigators will provide an evidence for the probiotics ingestion promote the rate of IM regression in patients after H. pylori eradication.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

What are already know

  1. H. pylori-induced Wnt/beta-catenin cascades leads to gastric carcinogenesis.
  2. Nuclear beta-catenin and COX-2 expression correlated to the IM regression rate in human after H. pylori eradication.
  3. Administration of selective COX-2 inhibitos, celecoxib, results in partial IM regression in patients with long-term IM persistence after H. pylori eradication
  4. Certain miRNAs involve in gastric oncogenesis by targeting Wnt/beta-catenin signaling pathway.

What will be add

  1. The Wnt/beta-catenin oncogenesis induction is different between primary (GES-1), and cancer (AGS) gastric cells after H. pylori infection.
  2. Probiotics ameliorate or prevent H. pylori-induced gastric Wnt/beta-catenin/COX2 carcinogenesis signaling through regulating miRNAs.
  3. Probiotics administration improves regression rate in patients with CAG and IM after H. pylori successful eradication.

Diagram of clinical trial to evaluate probiotics ingestion improves H. pylori-related intestinal metaplasia (IM) in patients after eradication therapy

A.The dyspeptic patients receiving PES and biopsies will be continuously enrolled to find H. pylori infection and IM.

B.Investigators keep to allocate patients into probiotics-treatment and controls (each group 30 patients).

C.To compare the miRNA(s) serum levels in patients with IM regression and IM persistent by real-time PCR.

D.To analyze the significance of probiotics ingestion improves IM regression rate in the RTC.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Locations

  • Taiwan
      • Tainan, Taiwan, 704
        • Recruiting
        • National Cheng Kung University & Hospital
        • Contact:

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

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 20 years of age or older
  • Have undergone gastroscopy
  • First discovered H.pylori infection and intestinal metaplasia

Exclusion Criteria:

  • Massive bleeding is life-threatening
  • Gastric cancer
  • Previous treatment for H.pylori
  • Long-term use of non-steroidal anti-inflammatory drugs (eg, aspirin), and hydrogen ion pump inhibitors.

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: probiotic group
Routine eradicate treatment H. pylori, and probiotics (2 packs per day) for 6 months.
Other: probiotic
probiotic group give probiotics (2 packs per day) for 6 months.
Placebo Comparator: control group
Only routine eradicate treatment H. pylori.
Other: probiotic
probiotic group give probiotics (2 packs per day) for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The IM regression rate one year after H. pylori eradication
Time Frame: Eligible participants allocated to treat or non-treat groups. The panendoscopy was performed one year later.

H. pylori-infected participants (n=100) with IM received successful H. pylori eradication.

Group I (n=50) given oral probiotics 1 pack bid for 6 months, Group II did not treat.

The 2nd panendoscopy followed at one year later to evaluate IM status using Updated Sydney System Score.
Eligible participants allocated to treat or non-treat groups. The panendoscopy was performed one year later.

Collaborators and Investigators

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

Sponsor

National Cheng-Kung University Hospital

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)

March 20, 2024

Primary Completion (Estimated)

July 31, 2026

Study Completion (Estimated)

July 31, 2030

Study Registration Dates

First Submitted

July 6, 2022

First Submitted That Met QC Criteria

September 15, 2022

First Posted (Actual)

September 16, 2022

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A-BR-106-085

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The whole IPD will be shared after 2026.

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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