Influence of Bile Acids on Bacterial Uptake in Functional Dyspepsia

Functional Dyspepsia Clinical Trial

Official title:

Translocation of Microorganisms in Duodenal Biopsies of Healthy Volunteers and Patients With Functional Dyspepsia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03296267
• Other study ID #: s56880
• Status: Recruiting
• Phase: N/A
• First received: September 18, 2017
• Last updated: October 4, 2017
• Start date: January 2, 2017
• Est. completion date: April 20, 2018

Study information

• Verified date: September 2017
• Source: Universitaire Ziekenhuizen Leuven
• Contact: Dorien Beeckmans, PhD
• Phone: +3216 37 73 11
• Email: dorien.beeckmans[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In up to half of patients seen by gastroenterologists, routine examinations fail to find an underlying organic, systemic, or metabolic disease that readily explains the symptoms. These patients are referred to as patients with disorders of gastrointestinal function, of which functional dyspepsia (FD) is one of the most common. Despite intensive research to investigate various pathophysiological mechanisms of this disease, the pathogenesis remains obscure. The investigators recently demonstrated increased duodenal permeability in FD patients, as assessed by mounting routine endoscopic duodenal biopsy specimens into Ussing chambers to measure transepithelial electrical resistance and passage of a paracellular fluorescent probe. Impaired intestinal barrier function can lead to increased uptake of luminal substances which can induce an immunological response in the mucosa. Interestingly, using transmission electron microscopy (TEM) in duodenal biopsies, the investigators recently observed the presence of a yet to be identified microorganism inside the epithelium and the lamina propria of a subset of FD patients (unpublished observations), suggesting increased translocation of microorganisms.

The aim of the project is to investigate whether FD patients display increased translocation of microorganisms in duodenal biopsies. The investigators will also test the effect of bile acid on translocation of microorganisms and therefore include 20 FD patients and 20 age- and gender-matched healthy volunteers in this study.

Description:

The participants will be expected on the department endoscopy of the University Hospital Gasthuisberg, Leuven, Belgium. They are asked to fill in a bundle of questionnaires concerning physical complaints, depression, anxiety (disturbances), pain/disease, body/interoceptive awareness, trauma/abuse and personality. Endoscopy will be performed and up to 8 biopsies will be obtained from the duodenum. All endoscopies will be performed by an experienced endoscopist. Biopsies will be mounted in Ussing chambers and the mucosal compartment will be exposed to commercially available fluorescein-conjugated microorganisms. Uptake of microorganisms will be evaluated by analyzing the serosal compartment and by confocal microscopy of the biopsies. These experiments will also be performed in combination with exposure to bile acids separately and jointly, to assess if bacterial translocation can be exacerbated by these endogenous luminal factors individually and synergistically.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 20, 2018
• Est. primary completion date: April 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Three days before the measurement: no smoking and drinking alcohol

• 12 hours before the measurement: no drinking and eating

Exclusion Criteria:

• symptoms or history of gastrointestinal disease

• first degree relatives with celiac disease

• diabetes mellitus

• allergy/atopy (eczema, asthma, allergic rhinoconjunctivitis)

• coagulation disorders/anticoagulant therapy

• first degree relatives with Crohn's disease or type I diabetes mellitus.

• intake of antihistamines, ketotifen, cromoglycate, acetylsalicylates, NSAIDs, anticholinergics, theophylline, ß2-agonists, codeine or opioid derivatives for at least 2 weeks prior to the gastroscopy

• Intake of steroid or immunosuppressive drugs in the last 6 months

Related Conditions & MeSH terms

• Dyspepsia
• Functional Dyspepsia
• Gastritis

Intervention

Procedure:
• Gastroduodenoscopy
Gastroduodenoscopy with duodenal biospies: A tube is placed via the mouth into the second part of the duodenum. Biopsy forceps is used to take duodenal biopsies.

Locations

Country	Name	City	State
Belgium	Translational Research center for Gastrointestinal Disorders (TARGID)	Leuven	Vlaams-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bacterial uptake in the duodenal biopsy measured by fluorescent intensity at the basolateral side of the ussing chamber setup.	duodenal uptake of fluorescein conjugated microorganisms	120 minutes
Secondary	duodenal permeability assessed by measuring transepithelial electrical resistance in the Ussing chamber setup	transepithelial electrical resistance	120 minutes