PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

Study Overview
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Brief Summary
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Prospective interventional study of the effect of PPI on the duodenal microbiome in healthy volunteers and functional dyspepsia patients

Detailed Description
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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.

Official Title
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Effect of Proton Pump Inhibitors on the Duodenal Microbiome in Healthy Volunteers and Functional Dyspepsia Patients

Conditions
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Dysbiosis

Intervention / Treatment
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* Drug: Pantoprazole 40mg
* Other: PPI withdrawal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pantoprazole 40mg in healthy volunteers<br>Peroral Pantoprazole 40mg once daily for 4 weeks | Drug: Pantoprazole 40mg<br>* Peroral Pantoprazole 40mg once daily during 28 days<br>* Other names: Pantomed;|
| Other: Pantoprazole 40mg in functional dyspepsia<br>Peroral Pantoprazole 40mg once daily for 4 weeks | Drug: Pantoprazole 40mg<br>* Peroral Pantoprazole 40mg once daily during 28 days<br>* Other names: Pantomed;|
| Other: PPI-withdrawal in functional dyspepsia<br>no PPI for 8 weeks | Other: PPI withdrawal<br>* PPI withdrawal for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in microbiota composition | Change in microbiota composition in the duodenum (lumen and mucosa) and feces | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mucosal inflammation | Change in mucosal inflammation (using immunohistochemistry) of the duodenum | 4 weeks | 
| Change in mucosal permeability | Change in mucosal permeability (using ussing chambers) of the duodenum | 4 weeks | 
| Change in bile acid composition | Change in bile acid composition in the duodenum | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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duodenum, microbiome, proton pump inhibitor