Esophageal capsaïcin Infusion and Mucosal Integrity

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

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.

Study Overview

• Status: Completed
• Conditions: Electric Impedance; Pain Measurement; Capsaicin; Esophagus; TRPV1 Protein, Human; Intracellular Space; Microscopy, Electron
• Intervention / Treatment: Other: Capsaicin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Capsaicin; 1,5 mg capsaicin in 30 minutes	Other: Capsaicin; capsaicin 1,5 mg
PLACEBO_COMPARATOR: Placebo; 75 ml placebo (0,9 % saline) in 30 minutes	Other: Placebo; 0,9% saline 75 ml

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Jose Conchillo, MD, PhD, Maastricht University Medical Center (MUMC+)

Publications and helpful links

General Publications

• Alleleyn AME, Keszthelyi D, Rinsma NF, Cseko K, Kajtar B, Helyes Z, Winkens B, Masclee AAM, Conchillo JM. The Potential Role for Impaired Mucosal Integrity in the Generation of Esophageal Pain Using Capsaicin in Humans: An Explorative Study. Clin Transl Gastroenterol. 2022 May 1;13(5):e00488. doi: 10.14309/ctg.0000000000000488.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: October 30, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (ESTIMATE): November 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 16, 2017
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: METC 152005