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PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

Primary Purpose

Dysbiosis

Status

Completed

Phase

Phase 4

Locations

Belgium

Study Type

Interventional

Intervention

Pantoprazole 40mg

PPI withdrawal

About this trial

This is an interventional treatment trial for Dysbiosis focused on measuring duodenum, microbiome, proton pump inhibitor

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

UZ Leuven

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

Pantoprazole 40mg in healthy volunteers

Pantoprazole 40mg in functional dyspepsia

PPI-withdrawal in functional dyspepsia

Arm Description

Peroral Pantoprazole 40mg once daily for 4 weeks

no PPI for 8 weeks

Outcomes

Primary Outcome Measures

Change in microbiota composition

Change in microbiota composition in the duodenum (lumen and mucosa) and feces

Secondary Outcome Measures

Change in mucosal inflammation

Change in mucosal inflammation (using immunohistochemistry) of the duodenum

Change in mucosal permeability

Change in mucosal permeability (using ussing chambers) of the duodenum

Change in bile acid composition

Change in bile acid composition in the duodenum

Full Information

NCT ID

NCT03545243

First Posted

April 24, 2018

Last Updated

September 23, 2020

Sponsor

Universitaire Ziekenhuizen KU Leuven

1. Study Identification

Unique Protocol Identification Number

NCT03545243

Brief Title

PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

April 23, 2018 (Actual)

Primary Completion Date

March 8, 2020 (Actual)

Study Completion Date

September 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Universitaire Ziekenhuizen KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dysbiosis

Keywords

duodenum, microbiome, proton pump inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

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)

Allocation

Non-Randomized

Enrollment

79 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pantoprazole 40mg in healthy volunteers

Arm Type

Other

Arm Description

Peroral Pantoprazole 40mg once daily for 4 weeks

Arm Title

Pantoprazole 40mg in functional dyspepsia

Arm Type

Other

Arm Description

Peroral Pantoprazole 40mg once daily for 4 weeks

Arm Title

PPI-withdrawal in functional dyspepsia

Arm Type

Other

Arm Description

no PPI for 8 weeks

Intervention Type

Drug

Intervention Name(s)

Pantoprazole 40mg

Other Intervention Name(s)

Pantomed

Intervention Description

Peroral Pantoprazole 40mg once daily during 28 days

Intervention Type

Other

Intervention Name(s)

PPI withdrawal

Intervention Description

PPI withdrawal for 8 weeks

Primary Outcome Measure Information:

Title

Change in microbiota composition

Description

Change in microbiota composition in the duodenum (lumen and mucosa) and feces

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Change in mucosal inflammation

Description

Change in mucosal inflammation (using immunohistochemistry) of the duodenum

Time Frame

4 weeks

Title

Change in mucosal permeability

Description

Change in mucosal permeability (using ussing chambers) of the duodenum

Time Frame

4 weeks

Title

Change in bile acid composition

Description

Change in bile acid composition in the duodenum

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tim Vanuytsel, MD PhD

Organizational Affiliation

UZ Leuven

Official's Role

Principal Investigator

Facility Information:

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

33346007

Citation

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.

Results Reference

derived

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PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

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