Ignite Creation Date:
2024-05-06 @ 10:02 AM
Last Modification Date:
2024-10-26 @ 12:23 PM
Study NCT ID:
NCT03142620
Status:
UNKNOWN
Last Update Posted:
2017-05-05
First Post:
2015-02-09
Brief Title:
Effect of Vitamin D on Drug Resistant Helicobacter Pylori HP Eradication Study
Sponsor:
Chinese University of Hong Kong
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
Delineation of Therapeutic Potential and the Causal Relationship Between Vitamin D and Helicobacter Pylori HP Infection and Gastritis
Status:
UNKNOWN
Status Verified Date:
2017-05
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
vDHp
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 1α25-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 1α25-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
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 1α25-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 1α25-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 1and 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 testRUT
2 Gastric biopsies and blood collectionWeek 0 V1 At baseline up to 5 ml of fasting blood sample will be collected for study aim 1 for plasma 125-hydroxylvitamin using Enzyme linked immunosorbent assayELISA
During endoscopy twelve gastric biopsies6 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 ELISART-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 regimenEsomeprazole 40 mg bid levofloxacin 500mg daily amoxicillin 1000mg bid for 10 daysLiou 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 125-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 005 were considered statistically significant
There are three time-points in this study Week 0 Visit 0 and Visit 1and 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 testRUT
2 Gastric biopsies and blood collectionWeek 0 V1 At baseline up to 5 ml of fasting blood sample will be collected for study aim 1 for plasma 125-hydroxylvitamin using Enzyme linked immunosorbent assayELISA
During endoscopy twelve gastric biopsies6 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 ELISART-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 regimenEsomeprazole 40 mg bid levofloxacin 500mg daily amoxicillin 1000mg bid for 10 daysLiou 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 125-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 005 were considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None