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

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.