PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

Phase 4

Completed

• Conditions: Dysbiosis
• Interventions: Other: PPI withdrawal; Drug: Pantoprazole 40mg

• Registration Number: NCT03545243
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

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 Timeline

• Study Start: 2018-04-23
• Study First Submitted: 2018-04-24
• Study First Submitted QC: 2018-05-22
• Study First Posted: 2018-06-04
• Primary Completion: 2020-03-08
• Status Verified: 2020-09
• Study Completion: 2020-09-22
• Last Update Submitted: 2020-09-23
• Last Update Posted: 2020-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PPI-withdrawal in functional dyspepsia	PPI withdrawal	no PPI for 8 weeks
Pantoprazole 40mg in healthy volunteers	Pantoprazole 40mg	Peroral Pantoprazole 40mg once daily for 4 weeks
Pantoprazole 40mg in functional dyspepsia	Pantoprazole 40mg	Peroral Pantoprazole 40mg once daily for 4 weeks

Primary Outcome Measures

Name	Time	Method
Change in microbiota composition	4 weeks	Change in microbiota composition in the duodenum (lumen and mucosa) and feces

Secondary Outcome Measures

Name	Time	Method
Change in mucosal permeability	4 weeks	Change in mucosal permeability (using ussing chambers) of the duodenum
Change in bile acid composition	4 weeks	Change in bile acid composition in the duodenum
Change in mucosal inflammation	4 weeks	Change in mucosal inflammation (using immunohistochemistry) of the duodenum

Trial Locations

Locations (1)

UZ Leuven; 🇧🇪 Leuven, Belgium