Delineation of Therapeutic Potential and the Causal Relationship Between Vitamin D and Helicobacter Pylori (HP) Infection and Gastritis

Chinese University of Hong Kong1 site in 1 country96 target enrollmentStarted: March 2015Last updated: May 5, 2017

Conditions

Interventions

Drugs

Trial Snapshot

Phase: Phase 3
Sponsor: Chinese University of Hong Kong
Enrollment: 96
Locations: 1
Primary Endpoint: The eradication status of H. pylori infection

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

Brief Summary

Background:

Helicobacter pylori infection, which affects over 50% of the global population, is one of the most prevalent infectious diseases in the world. H. pylori infection causes chronic active gastritis and is associated with peptic ulcer, lymphoma of the mucosa-associated lymphoid tissue and gastric cancer. The colonization of H. pylori in the hostile gastric environment is determined by the complex interactions among bacterial, environmental and host factors. Because of the emergence of antibiotic resistance and adverse drug reactions such as diarrhea, the successful rates with standard triple therapy for H. pylori eradication are falling.

Vitamin D or its analogues was found to induce autophagy in keratinocytes, macrophages, and various cancer cell types. Our preliminary findings indicated that 1α,25-dihydroxyvitamin D3 could induce cathelicidin expression and autophagy in cultured human gastric epithelial HFE-145 cells and reduced the intracellular survival of H. pylori in a co-culture system. It was also found that cathelicidin alone reduced the survival of drug-resistant strain of H. pylori. 1α,25-dihydroxyvitamin D3 also significantly reduced H. pylori colonization in mice, perhaps through the induction of cathelicidin in the stomach. These findings suggest that vitamin D not only could control H. pylori but also its drug-resistant strains in humans.

Emerging evidence suggest that vitamin D might be a cost-effective prophylactic and possibly therapeutic antimicrobial agent for the control and eradication of H. pylori. Since vitamin D acts through mechanisms independent of standard antibiotics, it is expected that vitamin D will be equally efficacious for controlling and eradicating drug-resistant strains of H. pylori. The investigators herein propose that vitamin D in combination of standard antimicrobial therapeutics could improve the eradication rates of drug-resistant H. pylori.

Detailed Description

Study methods:

There are three time-points in this study: Week 0 (Visit 0 and Visit 1)and Week 4 (Visit 2). In week 0, the investigators will do demographic assessment, baseline gastric biopsies and fasting blood sample collection, and randomization of treatment. In week 4, gastric biopsies and fasting blood sampling will be repeated. Details are as follows:

• Demographic assessment (Week 0, V 0) Demographic assessment (age, gender, smoking and alcohol drinking history) and anthropometric measurements (height, weight) and comorbidities will be recorded. Suitable patients will be invited to sign the consent.

Endoscopies (Week 0, 4; V1, V2) Patients will undergo overnight fast before endoscopy. Subjects will be given sedation and local analgesia to reduce discomfort during endoscopic procedures. H. pylori status will be determined by histology examination and rapid urease test(RUT).
Gastric biopsies and blood collection(Week 0, V1) At baseline, up to 5 ml of fasting blood sample will be collected for study aim 1) for plasma 1,25-hydroxylvitamin using Enzyme linked immunosorbent assay(ELISA).

During endoscopy, twelve gastric biopsies(6 biopsies at corpus and 6 biopsies at antrum respectively) will be taken for evaluating the mRNA and protein expression of vitamin D receptors, vitamin-D binding protein and cathelicidin by RT-PCR, immunohistochemistry stain (IHC) and antibiotic sensitivity test at baseline. 3. Randomization of treatment (Week 0, V1)

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to 80 Years (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

•Patient with H. pylori infection who fails to eradicate by standard triple therapy as confirmed by Urea Breath Test. Age 18-80
•Provision of written consent

Exclusion Criteria

•Current Use of Vitamin D supplement or any agents that can induce cathelicidin expression, e.g. butyrate related compounds
•Subject of child-bearing potential who is pregnant or intends to become pregnant during the trial period,
•Lactating female,
•Known hypersensitivity to PPI or antibiotics,
•Use of PPI or NSAID in the past 4 weeks,
•Malignancy,
•Subject has any condition that, at the discretion of the investigator, would preclude participation in the trial.