Functional Dyspepsia and Symptom Perception

Symptom Perception in Patients With Functional Dyspepsia: Involvement of the TRPV-1 Neuropeptide Pathway

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.

Study Overview

• Status: Unknown
• Conditions: Dyspepsia

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Annick Alleleyn, MD; Phone Number: +31433884190; Email: a.alleleyn@maastrichtuniversity.nl
• Study Contact Backup: Name: Fabiënne Smeets, MD; Email: fabienne.smeets@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6202 AZ
    • Recruiting
    • Maastricht University Medical Center (MUMC+)
    • Contact: Annick Alleleyn, MD; Phone Number: +31433884190; Email: a.alleleyn@maastrichtuniversity.nl
    • Contact: Fabiënne Smeets, MD; Email: fabienne.smeets@maastrichtuniversity.nl
    • Principal Investigator: Jose Conchillo, MD PhD
  • Sittard-Geleen, Netherlands
    • Not yet recruiting
    • Zuyderland Medical Center
    • Contact: Annick Alleleyn, MD; Phone Number: +31433884190; Email: a.alleleyn@maastrichtuniversity.nl
    • Contact: Fabiënne Smeets, MD; Email: fabienne.smeets@maastrichtuniversity.nl
  • Tilburg, Netherlands
    • Not yet recruiting
    • St. Elisabeth Medical Center
    • Contact: Annick Alleleyn, MD; Phone Number: +31433884190; Email: a.alleleyn@maastrichtuniversity.nl
    • Contact: Fabiënne Smeets, MD; Email: fabienne.smeets@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

50 patients with functional dyspepsia and 20 healthy controls will be included

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy controls
Patients with functional dyspepsia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TRPV-1 neuropeptide pathway (TRPV-1 and mucosal neuropeptides)	The primary outcome measure is the TRPV-1 neuropeptide pathway which includes both TRPV-1 and mucosal neuropeptide concentrations (e.g. substance P, somatostatin), assessed with real time polymerase chain reaction (PCR) and radioimmunoassay respectively.	Test day 1: mucosal biopsies are taken during upper gastrointestinal endoscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom scores for psychopathology	The Patient Health Questionnaire 9 (PHQ-9) and GAD-7 questionnaires will be used for the assessment of depressive and anxiety disorders respectively. During 7 consecutive days a digital device will be carried out for assessment of symptoms several times a day (experience sampling method/ESM).	14-day period between testday 1 and testday 2
Symptom scores for dyspepsia	Dyspeptic symptoms will be measured with two questionnaires to acquire more detailed information about complaints in patients with functional dyspepsia. The dyspepsia symptom questionnaire and the symptom checklist of the Nepean Dyspepsia Index will be used to grade the presence and intensity of dyspeptic symptoms. In addition, participants will report dyspeptic symptoms during 14 consecutive days in an end-of-day diary. During 7 consecutive days a digital device will be carried out for assessment of symptoms several times a day (experience sampling method/ESM).	14-day period between testday 1 and testday 2
Symptom scores for quality of life	Quality of life will be assessed with the Health Survey 26 (SF-36) questionnaire.	This questionnaire is fulfilled once, in the 14-day period between testday 1 and testday 2
Postprandial symptoms after ingestion of a standardized meal		Testday 2: Postprandial symptoms are scored using a Likert scale at 15-minute intervals for a period of 240 minutes postprandial.
In vivo gastroduodenal and small intestinal permeability	Gastroduodenal en small intestinal permeability will be assessed with a multisugar test.	Day before testday 2
Transcription of genes encoding for proteins involved in mucosal barrier function and symptom perception		Testday 1: gastric and duodenal biopsies are taken during upper gastrointestinal endoscopy.
Serotonin metabolism in mucosal tissue		Testday 1: gastric and duodenal biopsies are taken during upper gastrointestinal endoscopy
Serotonin metabolism in plasm		Testday 2: blood samples for serotonin analyses are taken preprandial and every 30 minutes after intake of a standardized meal during 240 minutes postprandial.
Gastric emptying for solids using the 13C-sodium octanoate stable isotope breath test		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.

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Jose Conchillo, MD, PhD, Maastricht University Medical Center, Maastricht, The Netherlands

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: July 29, 2015
• First Submitted That Met QC Criteria: August 12, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 12, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia
• Other Study ID Numbers: METC142070