Clinical trial NCT02522000: Functional Dyspepsia and Symptom Perception
Official title: Symptom Perception in Patients With Functional Dyspepsia: Involvement of the TRPV-1 Neuropeptide Pathway
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Dyspepsia
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2015-08-13
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 50 patients with functional dyspepsia and 20 healthy controls will be included

Brief summary: Functional dyspepsia (FD) is a heterogeneous disorder with multifactorial pathophysiology. Patients with FD have visceral hypersensitivity to mechanical and chemical stimuli. Several previous studies have described an increased chemosensitivity to oral capsaicin ingestion. Capsaicin is a natural agonist of TRPV-1 receptors present on afferent sensory neurons. Activation of the TRPV-1 receptor by capsaicin or other agonists results in the release of several neuropeptides (i.e. substance P, somatostatin). Besides, increased duodenal permeability and disruption of tight junction structure in FD patients compared to healthy volunteers has been reported in a recent study. In this observational study investigators will evaluate the role of the TRPV-1 neuropeptide pathway in patients with functional dyspepsia and healthy controls.


Eligibility criteria: Healthy volunteers

Inclusion criteria:

- No gastrointestinal symptoms or history of gastrointestinal disease meeting ROME III criteria for functional dyspepsia and Irritable Bowel Syndrome (IBS).

Exclusion criteria:

* Inability to stop the intake of nonsteroidal antiinflammatory drugs (NSAIDs) within 14 days prior to endoscopy and within two days prior to multi-sugar test.
* Inability to stop the intake of medication affecting gastrointestinal function (e.g. proton pump inhibitors, prokinetics, laxatives) within 5 days prior to endoscopy, multi-sugar test and combined meal- and gastric emptying test
* Current use of antidepressants
* Medical history of diabetes mellitus
* Medical history of coeliac disease
* Organic disease at upper gastrointestinal endoscopy (i.e. erosive esophagitis, Barrett's esophagus, benign esophageal stricture, Schatzki ring, esophageal carcinoma, esophageal candidiasis, gastric ulcer, gastric erosions, gastric cancer, duodenal erosions or duodenal ulcer)
* First-degree family members with diabetes mellitus type I, coeliac disease, Crohn's disease or ulcerative colitis
* Medical history of food allergy or anamnestic evidence of food allergy
* Presence of coagulation disorders or use of the following anticoagulants: coumarin derivates, new oral anticoagulants (NOACs: dabigatran, apixaban and rivaroxaban), and clopidogrel (Patients or healthy controls using calcium carbasalate (acetylsalicylic acid 100mg 1dd1) are eligible to participate in the study. Patients or healthy controls using higher doses of calcium carbasalate will be excluded from the study).
* Dieting
* Pregnancy or lactation
* Smoking
* Excessive alcohol use (\>20 alcoholic consumptions/week) and inability to avoid use of alcohol in the 2 days prior to endoscopy and multi-sugar test

Functional dyspepsia patients

Inclusion criteria:

- Patients referred for upper gastrointestinal endoscopy by either general practitioners or physicians from the gastroenterology outpatient clinic and meeting ROME III criteria for functional dyspepsia.

Exclusion criteria:

* Inability to stop the intake of nonsteroidal antiinflammatory drugs (NSAIDs) within 14 days prior to endoscopy and within two days prior to multi-sugar test.
* Inability to stop the intake of medication affecting gastrointestinal function (e.g. proton pump inhibitors, prokinetics, laxatives) within 5 days prior to endoscopy, multi-sugar test and combined meal- and gastric emptying test
* Current use of antidepressants
* Medical history of diabetes mellitus
* Medical history of coeliac disease
* Organic disease at upper gastrointestinal endoscopy (i.e. erosive esophagitis, Barrett's esophagus, benign esophageal stricture, Schatzki ring, esophageal carcinoma, esophageal candidiasis, gastric ulcer, gastric erosions, gastric cancer, duodenal erosions or duodenal ulcer)
* First-degree family members with diabetes mellitus type I, coeliac disease, Crohn's disease or ulcerative colitis
* Medical history of food allergy or anamnestic evidence of food allergy
* Presence of coagulation disorders or use of the following anticoagulants: coumarin derivates, new oral anticoagulants (NOACs: dabigatran, apixaban and rivaroxaban), and clopidogrel (Patients or healthy controls using calcium carbasalate (acetylsalicylic acid 100mg 1dd1) are eligible to participate in the study. Patients or healthy controls using higher doses of calcium carbasalate will be excluded from the study).
* Dieting
* Pregnancy or lactation
* Smoking
* Excessive alcohol use (\>20 alcoholic consumptions/week) and inability to avoid use of alcohol in the 2 days prior to endoscopy and multi-sugar test

Primary outcomes:
measure: TRPV-1 neuropeptide pathway (TRPV-1 and mucosal neuropeptides)
timeFrame: Test day 1: mucosal biopsies are taken during upper gastrointestinal endoscopy
Secondary outcomes:
measure: Symptom scores for psychopathology
timeFrame: 14-day period between testday 1 and testday 2
measure: Symptom scores for dyspepsia
timeFrame: 14-day period between testday 1 and testday 2
measure: Symptom scores for quality of life
timeFrame: This questionnaire is fulfilled once, in the 14-day period between testday 1 and testday 2
measure: Postprandial symptoms after ingestion of a standardized meal
timeFrame: Testday 2: Postprandial symptoms are scored using a Likert scale at 15-minute intervals for a period of 240 minutes postprandial.
measure: In vivo gastroduodenal and small intestinal permeability
timeFrame: Day before testday 2
measure: Transcription of genes encoding for proteins involved in mucosal barrier function and symptom perception
timeFrame: Testday 1: gastric and duodenal biopsies are taken during upper gastrointestinal endoscopy.
measure: Serotonin metabolism in mucosal tissue
timeFrame: Testday 1: gastric and duodenal biopsies are taken during upper gastrointestinal endoscopy
measure: Serotonin metabolism in plasm
timeFrame: Testday 2: blood samples for serotonin analyses are taken preprandial and every 30 minutes after intake of a standardized meal during 240 minutes postprandial.
measure: Gastric emptying for solids using the 13C-sodium octanoate stable isotope breath test
timeFrame: Testday 2: Repeated measure: breath samples for analysis of gastric emptying are taken preprandial and every 15 minutes after intake of a standardized meal during 240 minutes postprandial.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center (MUMC+)
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medical Center
city: Tilburg
country: Netherlands
facility: St. Elisabeth Medical Center
Study officials:
affiliation: Maastricht University Medical Center, Maastricht, The Netherlands
name: Jose Conchillo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: