Esophageal capsaïcin Infusion and Mucosal Integrity

Study Overview
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Brief Summary
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Reflux is common, especially after large meals. In general, this can do no harm. However, if reflux occurs often and causes troublesome symptoms and or complications, it is called gastroesophageal reflux disease (GERD). Long exposure to gastric acid causes the mucosa of the esophagus to loose its integrity, which is thought to lead to the symptom of heartburn. Several food products can also impair the esophageal mucosa integrity and thereby influence reflux symptoms. One of these products is capsaicin, the pungent ingredient of red peppers. Use of capsaicin often leads to worsening of complaints in patients with GERD and can cause symptoms in healthy volunteers, possibly due to its effect on the mucosal integrity. In this study the investigators want to investigate the effect of capsaicin infusion on mucosal integrity. The investigators will evaluate mucosal impedance and the histology of the esophageal mucosa. In addition, the investigators also aim to assess the involvement of the TRPV1 receptor by evaluating the possible release of neuropeptides in the esophageal mucosa.

Official Title
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Effect of capsaïcin Infusion on Esophageal Mucosal Integrity - a Role for TRPV1-mediated Neuropeptides?

Conditions
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TRPV1 Protein, Human, Capsaicin, Electric Impedance, Esophagus, Intracellular Space, Pain Measurement, Microscopy, Electron

Intervention / Treatment
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* Other: Capsaicin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No history of gastrointestinal disease, especially gastro-esophageal reflux disease. BMI = 18-25 kg/m² Caucasian race Subject signed the informed consent form and is able to adhere to study protocol Exclusion Criteria: Age <18 years Erosive esophagitis or gastric ulceration during endoscopy on PPI in the past or during the experiment Use of regular (> 1 x per week) dietary capsaïcin (in additives as Tabasco/sambal/chili sauce or Indian, Mexican or Thai food dishes) Allergy to capsaïcin Use of medication affecting GI function (prokinetics) or antisecretory medication (PPI) within 3 days prior to endoscopy. Multisystem diseases (including severe cardiopulmonary disease, collagen diseases, coagulation disorders) Esophageal motility disorders Previous esophageal or gastric surgery Use of anticoagulants or a history of coagulopathy Pregnancy History of alcohol abuse or current excessive alcohol consumption (> 2 alcoholic beverages per day or > 14 alcoholic beverages per week)
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Capsaicin<br>1,5 mg capsaicin in 30 minutes | Other: Capsaicin<br>* capsaicin 1,5 mg<br>|
| Placebo Comparator: Placebo<br>75 ml placebo (0,9 % saline) in 30 minutes | Other: Placebo<br>* 0,9% saline 75 ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in mucosal integrity in the distal exposed esophagus during capsaicin infusion compared to control solution. | The primary outcome measure is the effect of capsaïcin infusion on mucosal integrity as reflected by baseline impedance in the distal exposed esophagus compared to control infusion. We hypothesize that capsaïcin infusion induces changes to the mucosa as reflected by a decrease in baseline impedance. | Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucosal integrity in the proximal non-exposed esophagus. | The effect of esophageal capsaïcin infusion on mucosal integrity as reflected by baseline impedance in the proximal non-exposed esophagus compared to control solution. | Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy | 
| Induction of dilated intercellular spaces (DIS) | The effect of esophageal capsaïcin infusion on the induction of dilated intercellular spaces (DIS) in the distal exposed and proximal non-exposed esophagus as measured with transmission electron microscopy (TEM). | Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy | 
| TRPV1 neuropeptide pathway | The differences in the TRPV1 neuropeptide pathway (substance P) by radioimmunoassay (RIA) during capsaïcin infusion or control solution in both the distal exposed and proximal non-exposed esophagus. | Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy | 
| Immunohistochemical expression of TRPV1 | The differences in immunohistochemical expression of TRPV1 during capsaïcin infusion or control solution in both the distal exposed and proximal non-exposed esophagus. | Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy | 
| Symptom scores | The effect of capsaïcin infusion on symptoms in healthy volunteers. | Testday 1 and 2: during capsaicin and placebo infusion. | 
| TRPV1 neuropeptide pathway | The differences in the TRPV1 neuropeptide pathway (CGRP) by radioimmunoassay (RIA) during capsaïcin infusion or control solution in both the distal exposed and proximal non-exposed esophagus. | Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy |