Functional Dyspepsia and Symptom Perception

Dyspepsia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02522000
• Other study ID #: METC142070
• Status: Recruiting
• Phase: N/A
• First received: July 29, 2015
• Last updated: August 12, 2015
• Start date: July 2015
• Est. completion date: July 2017

Study information

• Verified date: July 2015
• Source: Maastricht University Medical Center
• Contact: Annick Alleleyn, MD
• Phone: +31433884190
• Email: a.alleleyn[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Dyspepsia

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center (MUMC+)	Maastricht
Netherlands	Zuyderland Medical Center	Sittard-Geleen
Netherlands	St. Elisabeth Medical Center	Tilburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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.	No
Secondary	In vivo gastroduodenal and small intestinal permeability	Gastroduodenal en small intestinal permeability will be assessed with a multisugar test.	Day before testday 2	No
Secondary	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.	No
Secondary	Serotonin metabolism in mucosal tissue		Testday 1: gastric and duodenal biopsies are taken during upper gastrointestinal endoscopy	No
Secondary	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.	No
Secondary	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.	No