H. Pylori InfectionPhase 3vDHpNCT03142620
Effect of Vitamin D on Drug Resistant Helicobacter Pylori (HP) Eradication Study
A Phase 3 study testing Esomeprazole, Amoxicillin-Potassium Clavulanate Combination and Clarithromycin in people with H. Pylori Infection, run by Chinese University of Hong Kong at 1 site in Hong Kong.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- H. Pylori Infection
- What is being tested?
- Esomeprazole, Amoxicillin-Potassium Clavulanate Combination and Clarithromycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteHong Kong
- Study dates
- Mar 2015to Dec 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong
Justin C.Y. Wu, MBChB(CUHK), (852)3505 3476, justinwu@cuhk.edu.hk
Justin C.Y. Wu, MBChB(CUHK)
About this study
Official title: Delineation of Therapeutic Potential and the Causal Relationship Between Vitamin D and Helicobacter Pylori (HP) Infection and Gastritis
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.
Read more
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.
Read the 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.
- Randomization of treatment (Week 0, V1)
After all baseline investigations, patients will be randomly assigned to either
- Triple Therapy 10 days OR
- Triple Therapy 10 days plus one oral daily dose of vitamin D for 10 days OR
- 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.
- 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.
- Conditions
- H. Pylori Infection
- Being tested
- Esomeprazole, Amoxicillin-Potassium Clavulanate Combination, Clarithromycin, Vitamin D3
- Keywords
- Drug resistant H.pylori infection, vitamin D, gastritis
- Medical subject headings
- Gastritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsomeprazoleDrug
Also called Nexium
40mg twice daily
Amoxicillin-Potassium Clavulanate CombinationDrug
Also called Amoxicillin
1000mg twice daily
ClarithromycinDrug
Also called Klacid
500mg twice daily
Vitamin D3Drug
Also called Cholecalciferol
5000IU
| Study group | Role | What they receive |
|---|---|---|
| Triple Therapy 10 days | Active comparator | Esomeprazole 40mg, Amoxicillin-Potassium Clavulanate Combination 1000mg and clarithromycin 500mg for 10 days Receives: Drug: Esomeprazole; Drug: Amoxicillin-Potassium Clavulanate Combination; Drug: Clarithromycin |
| Triple Therapy 10 days+ vitamin D for 10 | Active comparator | Esomeprazole 40mg, Amoxicillin-Potassium Clavulanate Combination 1000mg and clarithromycin 500mg for 10 days
+ vitamin D3 IU for 10 days Receives: Drug: Esomeprazole; Drug: Amoxicillin-Potassium Clavulanate Combination; Drug: Clarithromycin; Drug: Vitamin D3 |
| Triple Therapy 10 days+vitamin D for 28 | Active comparator | Esomeprazole 40mg, Amoxicillin-Potassium Clavulanate Combination 1000mg and clarithromycin 500mg for 10 days
+ vitamin D3 IU for 28 days Receives: Drug: Esomeprazole; Drug: Amoxicillin-Potassium Clavulanate Combination; Drug: Clarithromycin; Drug: Vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 4
Secondary outcomes (1)
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 1α,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
Measured: Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2017
- Study startMar 2015
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for H. Pylori InfectionStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Justin Che-Yuen Wu, Chinese University of Hong Kong
- Investigators
- Justin CY Wu, MBChB(CUHK), Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03142620
- Sponsor's protocol ID
- HPVD
- Acronym
- vDHp
- Status last verified
- May 2017
- First submitted
- 9 Feb 2015
- Last updated
- 5 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delineation of Therapeutic Potential and the Causal Relationship Between Vitamin D and Helicobacter Pylori (HP) Infection and Gastritis
- ClinicalTrials.gov ID
- NCT03142620
- Acronym / sponsor ID
- vDHp / HPVD
- Conditions
- H. Pylori Infection
- Keywords
- Drug resistant H.pylori infection, vitamin D, gastritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 5 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- Randomization of treatment (Week 0, V1)
After all baseline investigations, patients will be randomly assigned to either
- Triple Therapy 10 days OR
- Triple Therapy 10 days plus one oral daily dose of vitamin D for 10 days OR
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Triple Therapy 10 days | Active comparator | Drug: Esomeprazole, Drug: Amoxicillin-Potassium Clavulanate Combination, Drug: ClarithromycinEsomeprazole 40mg, Amoxicillin-Potassium Clavulanate Combination 1000mg and clarithromycin 500mg for 10 days |
| Triple Therapy 10 days+ vitamin D for 10 | Active comparator | Drug: Esomeprazole, Drug: Amoxicillin-Potassium Clavulanate Combination, Drug: Clarithromycin, Drug: Vitamin D3Esomeprazole 40mg, Amoxicillin-Potassium Clavulanate Combination 1000mg and clarithromycin 500mg for 10 days + vitamin D3 IU for 10 days |
| Triple Therapy 10 days+vitamin D for 28 | Active comparator | Drug: Esomeprazole, Drug: Amoxicillin-Potassium Clavulanate Combination, Drug: Clarithromycin, Drug: Vitamin D3Esomeprazole 40mg, Amoxicillin-Potassium Clavulanate Combination 1000mg and clarithromycin 500mg for 10 days + vitamin D3 IU for 28 days |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (7 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsomeprazoleAlso: Nexium40mg twice daily | Drug | Triple Therapy 10 days, Triple Therapy 10 days+ vitamin D for 10, Triple Therapy 10 days+vitamin D for 28 |
| Amoxicillin-Potassium Clavulanate CombinationAlso: Amoxicillin1000mg twice daily | Drug | Triple Therapy 10 days, Triple Therapy 10 days+ vitamin D for 10, Triple Therapy 10 days+vitamin D for 28 |
| ClarithromycinAlso: Klacid500mg twice daily | Drug | Triple Therapy 10 days, Triple Therapy 10 days+ vitamin D for 10, Triple Therapy 10 days+vitamin D for 28 |
| Vitamin D3Also: Cholecalciferol5000IU | Drug | Triple Therapy 10 days+ vitamin D for 10, Triple Therapy 10 days+vitamin D for 28 |
Primary outcome
The eradication status of H. pylori infection
Time frame: Week 4
The eradication status of H. pylori infection determined by histological examination of gastric tissues obtained by endoscopy at Week 4
1 secondary outcome
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
Time frame: Week 4
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2017.
- The Chinese University of Hong KongLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Justin CY Wu, MBChB(CUHK) principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Esomeprazole, Amoxicillin-Potassium Clavulanate Combination and Clarithromycin in people with H. Pylori Infection, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Justin CY Wu, MBChB(CUHK) ((852)3505 3476, justinwu@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The eradication status of H. pylori infection (time frame: Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2017.