Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03142620
Other study ID # HPVD
Secondary ID
Status Recruiting
Phase Phase 3
First received February 9, 2015
Last updated May 4, 2017
Start date March 2015
Est. completion date December 2017

Study information

Verified date May 2017
Source Chinese University of Hong Kong
Contact Justin CY Wu, MBChB(CUHK)
Phone (852)3505 3476
Email justinwu@cuhk.edu.hk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.

1. 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).

2. 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)

After all baseline investigations, patients will be randomly assigned to either

1. Triple Therapy 10 days OR

2. Triple Therapy 10 days plus one oral daily dose of vitamin D for 10 days OR

3. Triple Therapy 10 days plus one oral daily dose of vitamin D for 28 days.

Concealed allocation is achieved by an independent staff who assigns treatments. Study medications are dispensed as sealed packages in consecutive numbers. Medication adherence is measured by pill counts on V2.

4. Follow-up assessment and sample collections (Week 4, V2)

At week 4, patients will report their dyspeptic symptoms, gastric biopsies and fasting blood sampling will be repeated at the end of 4-week treatment for ELISA,RT-PCR and IHC analyses. H. pylori eradication will be confirmed by histological examination during endoscopy.

Remarks: For patient who fails to eradicate H. pylori infection at the end of study will be given levofloxacin-based triple therapy as rescue regimen(Esomeprazole 40 mg bid + levofloxacin 500mg daily, amoxicillin 1000mg bid) for 10 days.(Liou et al. 2010) Urea Breath Test (UBT) after 10 weeks and follow up appointment will be arranged to the patient.

Statistical analyses:

All continuous variables between the three treatment groups (levels of 25-hydroxylvitamin D3 and 1,25-hydroxylvitamin D3, mRNA and protein expression of vitamin D receptors, CYP24A1, CYP27B1, vitamin-D binding protein and Cathelicidin) will be compared using Kruskal Wallis test or ANOVA as deemed appropriate at individual time-point.

In addition, the changes of these parameters and clinical symptoms over time will be compared using repeated ANOVA. P-values <0.05 were considered statistically significant.


Recruitment information / eligibility

Status Recruiting
Enrollment 96
Est. completion date December 2017
Est. primary completion date December 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 80 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Esomeprazole
40mg twice daily
Amoxicillin-Potassium Clavulanate Combination
1000mg twice daily
Clarithromycin
500mg twice daily
Vitamin D3
5000IU

Locations

Country Name City State
Hong Kong Prince of Wales Hospital Hong Kong

Sponsors (1)

Lead Sponsor Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type Measure Description Time frame Safety issue
Primary The eradication status of H. pylori infection The eradication status of H. pylori infection determined by histological examination of gastric tissues obtained by endoscopy at Week 4 Week 4
Secondary Comparisons of the levels of 25-hydroxylvitamin D3 and 1,25-hydroxylvitamin D3, mRNA and protein expression of vitamin D receptors, CYP24A1, CYP27B1, vitamin-D binding protein and Cathelicidin before (Week 0) and after (Week 4) treatment Plasma level of 25-hydroxylvitamin D3 by ELISA
Gastric tissue levels of 1a,25-hydroxylvitamin D3 by ELISA
Gastric mRNA and protein level of vitamin D receptors, CYP24A1, CYP27B1, vitamin-D binding protein and cathelicidin by Real Time-PCR and IHC.
Clinical dyspeptic symptoms
Gastric tissue of antibiotic resistant strains by antibiotic sensitivity test
Week 4
See also
  Status Clinical Trial Phase
Active, not recruiting NCT06045494 - The Efficacy of Treatment for Helicobacter Pylori Infection in Preschooler by Yoghurt With LG21 N/A
Not yet recruiting NCT01449500 - Supplementation With L. Reuteri in H. Pylori Infected Adults N/A
Completed NCT01234389 - Immediate Detection of Helicobacter Infection With a New Electrochemical System. N/A
Not yet recruiting NCT05387005 - Screening Strategy for Gastric Cancer Prevention N/A
Not yet recruiting NCT02761005 - Eradication of H. Pylori Therapy Individualized by the Mutation of 23S rRNA of H. Pylori Phase 2
Withdrawn NCT02090738 - A Randomized, Open-label Study on Helicobacter Pylori Eradication With Standard Triple Regimen Plus Acetazolamide Phase 2
Recruiting NCT01335334 - H. Pylori Eradication Using Pyklear in Adults in El Paso, Texas: a Pilot Study Phase 4
Recruiting NCT05544396 - Study on the Probiotics Regulating miRNA in H. Pylori-induced Wnt/β-catenin Gastric Carcinogenesis. N/A
Recruiting NCT04713670 - Comparison of Vonoprazan-based Versus Lansoprazole-based Triple Therapy, High Dose Dual Therapy, Bismuth and Non-bismuth Quadruple Therapy in the First-line Treatment of Helicobacter Pylori Infection Phase 4
Recruiting NCT06045832 - Oral Helicobacter Pylori Eradication N/A
Completed NCT05453994 - Bismuth for PCAB-based H. Pylori Eradication
Recruiting NCT02328131 - European Registry on the Management of Helicobacter Pylori Infection
Completed NCT00197457 - Pepsinogens as the Early Marker of H. Pylori Eradication Phase 2
Not yet recruiting NCT06412640 - Optimization of Keverprazan-amoxicilli Dual Therapy for Helicobacter Pylori Phase 4
Completed NCT04036838 - ARJ C13 Urea Breath Test System Phase 2
Completed NCT06050824 - A Comparative Study Between Concomitant Versus Load Therapy in Eradication of Helicobacter Pylori Infection Phase 4
Completed NCT02767479 - Comparison of Rabeprazole and Esomperazole for the Eradication of H. Pylori Phase 3
Completed NCT01505127 - Efficacy of TAK-438, Amoxicillin and Clarithromycin in the First Line Eradication of H. Pylori Phase 3
Recruiting NCT05176821 - Eradication Efficacy and Safety of Two Rescue Treatments for Helicobacter Pylori Infection N/A
Completed NCT05002595 - H. Pylori Treatment Between Modified Quadruple Regimen and Tailored Therapy