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PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

Sponsor
Universitaire Ziekenhuizen Leuven (Other)
Overall Status
Completed
CT.gov ID
NCT03545243
Collaborator
(none)
79
Enrollment
1
Location
3
Arms
29
Actual Duration (Months)
2.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Pantoprazole 40mg
  • Other: PPI withdrawal
 Phase 4

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

Study Type:
Interventional
Actual Enrollment :
79 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Prospective interventional study with study procedures at inclusion, after a baseline period of 4 weeks and Pantoprazole therapy for 4 weeksProspective interventional study with study procedures at inclusion, after a baseline period of 4 weeks and Pantoprazole therapy for 4 weeks
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Effect of Proton Pump Inhibitors on the Duodenal Microbiome in Healthy Volunteers and Functional Dyspepsia Patients
Actual Study Start Date :
Apr 23, 2018
Actual Primary Completion Date :
Mar 8, 2020
Actual Study Completion Date :
Sep 22, 2020

Arms and Interventions

Arm Intervention/Treatment
Other: Pantoprazole 40mg in healthy volunteers

Peroral Pantoprazole 40mg once daily for 4 weeks

Drug: Pantoprazole 40mg
Peroral Pantoprazole 40mg once daily during 28 days
Other Names:
  • Pantomed

    		•
    Other: Pantoprazole 40mg in functional dyspepsia

    Peroral Pantoprazole 40mg once daily for 4 weeks

    Drug: Pantoprazole 40mg
    Peroral Pantoprazole 40mg once daily during 28 days
    Other Names:
  • Pantomed

    		•
    Other: PPI-withdrawal in functional dyspepsia

    no PPI for 8 weeks

    Other: PPI withdrawal
    PPI withdrawal for 8 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Change in microbiota composition [4 weeks]

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

    Secondary Outcome Measures

    1. Change in mucosal inflammation [4 weeks]

      Change in mucosal inflammation (using immunohistochemistry) of the duodenum

    2. Change in mucosal permeability [4 weeks]

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

    3. Change in bile acid composition [4 weeks]

      Change in bile acid composition in the duodenum

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 64 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UZ Leuven Leuven Belgium 3000

    Sponsors and Collaborators

    • Universitaire Ziekenhuizen Leuven

    Investigators

    • Principal Investigator: Tim Vanuytsel, MD PhD, UZ Leuven

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Universitaire Ziekenhuizen Leuven
    ClinicalTrials.gov Identifier:
    NCT03545243
    Other Study ID Numbers:
    • S60984/60953
    First Posted:
    Jun 4, 2018
    Last Update Posted:
    Sep 28, 2020
    Last Verified:
    Sep 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Universitaire Ziekenhuizen Leuven
    duodenum
    microbiome
    proton pump inhibitor
    Additional relevant MeSH terms:
    Dyspepsia
    Dysbiosis
    Pantoprazole

    Study Results

    No Results Posted as of Sep 28, 2020