DysbiosisPhase 4NCT03545243
PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia
A Phase 4 study testing Pantoprazole 40mg and PPI withdrawal in people with Dysbiosis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Prospective interventional study of the effect of PPI on the duodenal microbiome in healthy volunteers and functional dyspepsia patients Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Dysbiosis
- What is being tested?
- Pantoprazole 40mg and PPI withdrawal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 1 siteBelgium
- Study dates
- 23 Apr 2018to 22 Sep 2020
- Phase
- Phase 4
- 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 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects aged between 18 and 64 years inclusive
- Male or female (not pregnant or lactating and using contraception or postmenopausal)
- Normal bowel habits (defecation once every 3 days up to 3 times a day)
- Witnessed written informed consent
- Access to home freezer (-18 to -20°C)
- Capable to understand and comply with the study requirements
Who cannot join
- Active psychiatric symptoms (stable dose of single antidepressant allowed)
- Use of acid suppressive drugs (before starting Pantomed), immunosuppressants or antibiotics <3 months before sampling
- Use of drugs influencing stool consistency, NSAIDs, anti-allergy drugs, bile acid sequestrants or ursodeoxycholic acid <2 weeks before sampling
- Use of prokinetics <2 weeks before sampling (unless if ≤3/week)
- History of major abdominal surgery, including cholecystectomy but not appendectomy or splenectomy
- Personal or family (first-degree relative) history of diabetes mellitus type 1, celiac disease, inflammatory bowel disease, psoriasis, rheumatic or other auto-immune diseases (including therapy)
Show all 16Show fewer
- Allergy or atopy (eczema, asthma and/or allergic rhinoconjunctivitis) (including therapy)
- Kidney, liver or coagulation disorders
- Active coronary or peripheral artery disease
- Diabetes mellitus type 2 (including therapy)
- Active malignancy (including therapy)
- Known HIV, HBV or HCV infection (including therapy)
- Magnetizable objects (e.g. cochlear implants, neural stimulator, pacemaker, metal fragments or implants) or claustrophobia (MRI safety criteria with additional consent form, other procedures can still take place)
- Significant alcohol use (>10 units/weeks)
- Any use of alcohol or smoking ≤2 days before sampling
- Females who are pregnant or lactating, who are not using contraception and premenopausal
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Proton Pump Inhibitors on the Duodenal Microbiome in Healthy Volunteers and Functional Dyspepsia Patients
Prospective interventional study of the effect of PPI on the duodenal microbiome in healthy volunteers and functional dyspepsia patients
Read the detailed description
PPIs are the first-line therapy in functional dyspepsia (FD) but frequently (over-)prescribed with potential adverse events, especially in the long term. As C. difficile and CAP are important causes of morbidity, mortality and healthcare costs, it is important to study the underlying mechanisms of PPI-induced dysbiosis.
In this prospective interventional study, study procedures will be performed at inclusion (1), after a baseline period of 4 weeks (2) and after treatment with Pantoprazole (Pantomed®) 40mg once daily during 4 weeks (3) in healthy volunteers and FD patients. In addition, study procedures will be performed at inclusion (1) and after PPI-withdrawal for 8 weeks in refractory FD patients.
The investigators aim to assess alterations of the duodenal (mucosa-associated and luminal) microbiome with PPI therapy and to correlate changes in the duodenal microbiota with oral and fecal microbiota, bile acids, intestinal permeability and histology and biochemical variables.
The results from this study will help to unravel the onset and extent of dysbiosis and provide additional arguments not to prescribe or continue PPI without clear clinical indications, especially in cases where alternative regimens may be available or the benefits of PPI are uncertain.
- Conditions
- Dysbiosis
- Being tested
- Pantoprazole 40mg, PPI withdrawal
- Keywords
- duodenum, microbiome, proton pump inhibitor
- Medical subject headings
- Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pantoprazole 40mgDrug
Also called Pantomed
Peroral Pantoprazole 40mg once daily during 28 days
PPI withdrawalOther
PPI withdrawal for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pantoprazole 40mg in healthy volunteers | Other | Peroral Pantoprazole 40mg once daily for 4 weeks Receives: Drug: Pantoprazole 40mg |
| Pantoprazole 40mg in functional dyspepsia | Other | Peroral Pantoprazole 40mg once daily for 4 weeks Receives: Drug: Pantoprazole 40mg |
| PPI-withdrawal in functional dyspepsia | Other | no PPI for 8 weeks Receives: Other: PPI withdrawal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in microbiota composition
Change in microbiota composition in the duodenum (lumen and mucosa) and feces
Measured: 4 weeks
Secondary outcomes (3)
Change in mucosal inflammation
Change in mucosal inflammation (using immunohistochemistry) of the duodenum
Measured: 4 weeks
Change in mucosal permeability
Change in mucosal permeability (using ussing chambers) of the duodenum
Measured: 4 weeks
Change in bile acid composition
Change in bile acid composition in the duodenum
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2018
- Study start23 Apr 2018
- Primary completion8 Mar 2020
- Study completion22 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DysbiosisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Prospective interventional study with study procedures at inclusion, after a baseline period of 4 weeks and Pantoprazole therapy for 4 weeks
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Vanuytsel, MD PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03545243
- Sponsor's protocol ID
- S60984/60953
- Status last verified
- Sep 2020
- First submitted
- 24 Apr 2018
- Last updated
- 28 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wauters L, Ceulemans M, Frings D, Lambaerts M, Accarie A, Toth J, Mols R, Augustijns P, De Hertogh G, Van Oudenhove L, Tack J, Vanuytsel T. Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia. Gastroenterology. 2021 Apr;160(5):1521-1531.e9. doi: 10.1053/j.gastro.2020.12.016. Epub 2020 Dec 18.
PubMed 33346007
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Proton Pump Inhibitors on the Duodenal Microbiome in Healthy Volunteers and Functional Dyspepsia Patients
- ClinicalTrials.gov ID
- NCT03545243
- Acronym / sponsor ID
- S60984/60953
- Conditions
- Dysbiosis
- Keywords
- duodenum, microbiome, proton pump inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 23 Apr 2018 (actual)
- Primary completion
- 8 Mar 2020 (actual)
- Study completion
- 22 Sep 2020 (actual)
- First posted
- 4 Jun 2018 (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.
Prospective interventional study of the effect of PPI on the duodenal microbiome in healthy volunteers and functional dyspepsia patients
Detailed description
PPIs are the first-line therapy in functional dyspepsia (FD) but frequently (over-)prescribed with potential adverse events, especially in the long term. As C. difficile and CAP are important causes of morbidity, mortality and healthcare costs, it is important to study the underlying mechanisms of PPI-induced dysbiosis.
In this prospective interventional study, study procedures will be performed at inclusion (1), after a baseline period of 4 weeks (2) and after treatment with Pantoprazole (Pantomed®) 40mg once daily during 4 weeks (3) in healthy volunteers and FD patients. In addition, study procedures will be performed at inclusion (1) and after PPI-withdrawal for 8 weeks in refractory FD patients.
The investigators aim to assess alterations of the duodenal (mucosa-associated and luminal) microbiome with PPI therapy and to correlate changes in the duodenal microbiota with oral and fecal microbiota, bile acids, intestinal permeability and histology and biochemical variables.
The results from this study will help to unravel the onset and extent of dysbiosis and provide additional arguments not to prescribe or continue PPI without clear clinical indications, especially in cases where alternative regimens may be available or the benefits of PPI are uncertain.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Prospective interventional study with study procedures at inclusion, after a baseline period of 4 weeks and Pantoprazole therapy for 4 weeks
| Arm | Type | Receives |
|---|---|---|
| Pantoprazole 40mg in healthy volunteers | Other | Drug: Pantoprazole 40mgPeroral Pantoprazole 40mg once daily for 4 weeks |
| Pantoprazole 40mg in functional dyspepsia | Other | Drug: Pantoprazole 40mgPeroral Pantoprazole 40mg once daily for 4 weeks |
| PPI-withdrawal in functional dyspepsia | Other | Other: PPI withdrawalno PPI for 8 weeks |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Subjects aged between 18 and 64 years inclusive
- Male or female (not pregnant or lactating and using contraception or postmenopausal)
- Normal bowel habits (defecation once every 3 days up to 3 times a day)
- Witnessed written informed consent
- Access to home freezer (-18 to -20°C)
Key exclusion criteria (16 listed)
- Active psychiatric symptoms (stable dose of single antidepressant allowed)
- Use of acid suppressive drugs (before starting Pantomed), immunosuppressants or antibiotics <3 months before sampling
- Use of drugs influencing stool consistency, NSAIDs, anti-allergy drugs, bile acid sequestrants or ursodeoxycholic acid <2 weeks before sampling
- Use of prokinetics <2 weeks before sampling (unless if ≤3/week)
- History of major abdominal surgery, including cholecystectomy but not appendectomy or splenectomy
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 |
|---|---|---|
| Pantoprazole 40mgAlso: PantomedPeroral Pantoprazole 40mg once daily during 28 days | Drug | Pantoprazole 40mg in functional dyspepsia, Pantoprazole 40mg in healthy volunteers |
| PPI withdrawalPPI withdrawal for 8 weeks | Other | PPI-withdrawal in functional dyspepsia |
Primary outcome
Change in microbiota composition
Time frame: 4 weeks
Change in microbiota composition in the duodenum (lumen and mucosa) and feces
3 secondary outcomes
Change in mucosal inflammation
Time frame: 4 weeks
Change in mucosal permeability
Time frame: 4 weeks
Change in bile acid composition
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2020.
- Derived from this study: PubMed 33346007Wauters L, Ceulemans M, Frings D, Lambaerts M, Accarie A, Toth J, Mols R, Augustijns P, De Hertogh G, Van Oudenhove L, Tack J, Vanuytsel T. Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia. Gastroenterology. 2021 Apr;160(5):1521-1531.e9. doi: 10.1053/j.gastro.2020.12.016. Epub 2020 Dec 18.
- Individual participant dataSharing planned: Undecided
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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.
Tim Vanuytsel, MD PhD principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pantoprazole 40mg and PPI withdrawal in people with Dysbiosis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 6 inclusion and 16 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: finished, as of the sponsor's last update on 28 Sep 2020. 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 Belgium. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in microbiota composition (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03545243, which also lists 1 linked publication.
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 28 Sep 2020.