NCT03003234

Brief Summary

Functional dyspepsia (FD) is an extremely common disorder of gastrointestinal function. Recently, impaired duodenal mucosal integrity was reported as a potential pathophysiological mechanism in FD. However, the factors controlling duodenal mucosal integrity remain unknown. In this study, we evaluated whether the luminal bile salt content could play a role in impaired duodenal permeability in FD. Duodenal biopsies were obtained from 25 healthy volunteers (HV) and 25 FD patients. Biopsies were mounted in Ussing chambers to measure transepithelial resistance (TEER) and paracellular permeability using fluorescein isothiocyanate dextran (FITC-dx4, MW 4kDa). Expression of bile acid-sensing receptors (TGR5, VDR, PXR, FXR and CAR) in duodenal biopsies was measured by western blot and real time RT-PCR. Immunohistochemistry was used to evaluate eosinophil and mastcell infiltration in duodenal biopsies of FD patients and HV. Duodenal fluid aspirates were collected at fixed time points during 1 hour in fasted state and 1.5 hours after a liquid meal (Nutridrink, 200ml). Concentration and composition of the bile salt pool (including glycocholic acid (GC), taurocholic acid (TC), glycochenodeoxycholic acid (GCDC), taurochenodeoxycholic acid (TCDC), glycodeoxycholic acid (GDC), taurodeoxycholic acid (TDC), glycoursodeoxycholic acid (GUDC) and tauroursodeoxycholic acid (TUDC)) in these aspirates was evaluated by liquid chromatography-mass spectrometry-selected ion monitoring analysis (LC-MS/MS).

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Mar 2015

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2015

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

December 5, 2016

Completed
21 days until next milestone

First Posted

Study publicly available on registry

December 26, 2016

Completed
Last Updated

December 26, 2016

Status Verified

November 1, 2016

Enrollment Period

1.7 years

First QC Date

December 5, 2016

Last Update Submit

December 23, 2016

Conditions

Functional Dyspepsia

Outcome Measures

Primary Outcomes (10)

  • Duodenal mucosal transepithelial electrical resistance (Ohm*cm^2)

    Measurement for mucosal integrity

    2 hours

  • Duodenal paracellular passage of Fitc Dextran 4 kDa (pmol)

    Measurement for mucosal integrity

    2 hours

  • Glycocholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Taurocholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Glycochenodeoxycholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Taurochenodeoxycholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Glycodeoxycholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Taurodeoxycholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Glycoursodeoxycholic acid concentration (mM)

    Bile salt

    2.5 hours

  • Tauroursodeoxycholic acid concentration (mM)

    Bile salt

    2.5 hours

Secondary Outcomes (19)

  • Duodenal mucosal mastcell count (number of mastcells/mm^2 lamina propria)

    2 years

  • Duodenal mucosal eosinophil count (number of eosinophils/mm^2 lamina propria)

    2 years

  • RNA expression of Vitamin D receptor (VDR)

    2 years

  • RNA expression of bile acid receptor FXR

    2 years

  • RNA expression of bile acid receptor PXR

    2 years

  • +14 more secondary outcomes

Study Arms (1)

Duodenal fluid aspiration

OTHER
Procedure: DuodenogastroscopyDevice: Duodenal aspiration catheterDietary Supplement: Nutri drink

Interventions

DuodenogastroscopyPROCEDURE

Catheter goes through the mouth in the duodenum to take duodenal biopsies.

Duodenal fluid aspiration
Duodenal aspiration catheterDEVICE

Catheter goes through the nose in the duodenum to aspirate duodenal fluid in fasted and fed state.

Duodenal fluid aspiration
Nutri drinkDIETARY_SUPPLEMENT

Liquid meal of 200 ml.

Duodenal fluid aspiration

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • FD patients have to fulfill the Rome III criteria for functional dyspepsia.

You may not qualify if:

  • Symptoms or history of gastrointestinal disease (for healthy volunteers)
  • 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, β2-agonists, codeine or opioid derivatives for at least 2 weeks prior to the study.
  • Steroid or immunosuppressive drug intake any time in the last 6 months

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 5, 2016

First Posted

December 26, 2016

Study Start

March 1, 2015

Primary Completion

November 1, 2016

Study Completion

November 1, 2016

Last Updated

December 26, 2016

Record last verified: 2016-11

Data Sharing

IPD Sharing
Will not share