PPI and Microbiome in Healthy Volunteers and Functional Dyspepsia

Dysbiosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03545243
• Other study ID #: S60984/60953
• Status: Completed
• Phase: Phase 4
• Start date: April 23, 2018
• Est. completion date: September 22, 2020

Study information

• Verified date: September 2020
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: September 22, 2020
• Est. primary completion date: March 8, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Dysbiosis
• Dyspepsia

Intervention

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

Other:
• PPI withdrawal
PPI withdrawal for 8 weeks

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in microbiota composition	Change in microbiota composition in the duodenum (lumen and mucosa) and feces	4 weeks
Secondary	Change in mucosal inflammation	Change in mucosal inflammation (using immunohistochemistry) of the duodenum	4 weeks
Secondary	Change in mucosal permeability	Change in mucosal permeability (using ussing chambers) of the duodenum	4 weeks
Secondary	Change in bile acid composition	Change in bile acid composition in the duodenum	4 weeks