Intragastric pH and Bismuth Effect for H. Pylori Eradication

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. In Taiwan, there are around 3800 fresh cases annually, with about 5% of total cancers cases. Gastric cancer development is known to follow a multistate process from non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and carcinoma; H. pylori infection plays the key role of this carcinogenic process. Although H. pylori eradication would result in a marked gastric cancer reduction, treatment success using standard regimens has become more difficult in recent years, and increased antibiotic resistance is considered the most important reason for decreased treatment efficacy. As no specific new medications have been introduced in recent years, novel treatment regimens have been created using different combinations, durations and sequences of available medications. The addition of bismuth improved the cure rates despite a high prevalence of resistance, and resistance of H. pylori to bismuth has not been reported. Bismuth absorption is not required for efficacy in H. pylori treatment regimens, suggesting a local mechanism of action. The mechanisms of bismuth with responsible for rapid destruction of H. pylori within the stomach remain unclear. Knowledge of the mechanism of action of bismuth compounds against H. pylori would be beneficial in the development of improved treatment regimens in this era of declining eradication success rates. We conduct the pilot study to evaluate the bacteria fragments of H. pylori in specimen through electron microscopy after bismuth therapy and provide insight into the mechanism of action of pH on bismuth therapy. We also help to develop optimal H. pylori therapeutic strategies.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: (A)Bismuth; Drug: (B)Bismuth; Drug: (C)Bismuth; Drug: (D)Esomeprazole and Bismuth; Drug: (E)Esomeprazole and Bismuth; Drug: (F)Esomeprazole and Bismuth; Other: (G)Control

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Age 20-69
2. Confirmed H. pylori infection by urea breath test or previous histology
3. Scheduled endoscopy
4. Mentally competent to be able to understand the consent form for individuals equal to or older than 20
5. Able to communicate with study staff for individuals equal to or older than 20
6. Without history of gastric cancer Exclusion criteria

1.History of gastric cancer

Deferral criteria:

1. Having received antibiotic treatment in the previous 15 days
2. Need of time to decide participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: (A)Bismuth; (A)Bismuth (120mg/tab) 1 dose prior 1 hr before endoscopy	Drug: (A)Bismuth; Other Names: (A)Active Comparator-Bismuth
Active Comparator: (B)Bismuth; (B)Bismuth (120mg/tab) 1 dose in the morning and endoscopy in the afternoon	Drug: (B)Bismuth; Other Names: (B)Active Comparator-Bismuth
Active Comparator: (C)Bismuth; (C)Bismuth (120mg/tab) q.i.d. and endoscopy the next day	Drug: (C)Bismuth; Other Names: (C)Active Comparator-Bismuth
Active Comparator: (D)Esomeprazole and Bismuth; (D)3 days esomeprazole (40mg/tab) q.i.d. followed by bismuth (120mg/tab) 1 dose prior 1 hr before endoscopy	Drug: (D)Esomeprazole and Bismuth; Other Names: (D)Active Comparator-Esomeprazole and Bismuth
Active Comparator: (E)Esomeprazole and Bismuth; (E)3 days esomeprazole (40mg/tab) q.i.d. followed by bismuth (120mg/tab) 1 dose in the morning and endoscopy in the afternoon	Drug: (E)Esomeprazole and Bismuth; Other Names: (E)Active Comparator-Esomeprazole and Bismuth
Active Comparator: (F)Esomeprazole and Bismuth; (F)3 days esomeprazole (40mg/tab) q.i.d. followed by bismuth (120mg/tab) q.i.d. and endoscopy the next day	Drug: (F)Esomeprazole and Bismuth; Other Names: (F)Active Comparator-Esomeprazole and Bismuth
Other: (G)Control; (G)These patients underwent endoscopy due to abdominal discomfort or other symptoms and did not have cancers in the digestive tract after series of workup.	Other: (G)Control; Other Names: (G)Other-Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The morphological changes of post-drug H. pylori by electron microscopy.	Endoscopy: The biopsy procedure protocol specified sampling gastric mucosa in the locations of gastric antrum, body and cardia (two specimens from each location). Specimens would be sent for electron microscopy. Electron microscopy: Bacteria fragments of H. pylori would be observed.	3 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Ministry of Science and Technology, Taipei, Taiwan
• Investigators: Principal Investigator: Tsung-Hsien Chiang, MD, M.Sc., National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2016
• Primary Completion (Actual): October 18, 2017
• Study Completion (Actual): February 20, 2019

Study Registration Dates

• First Submitted: July 27, 2016
• First Submitted That Met QC Criteria: September 4, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: May 30, 2019
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Electron Microscopy; Bismuth
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antacids; Esomeprazole; Bismuth
• Other Study ID Numbers: 201512127MINC