Clinical trial NCT02603783: Esophageal capsaïcin Infusion and Mucosal Integrity
Official title: "Effect of capsaïcin Infusion on Esophageal Mucosal Integrity - a Role for TRPV1-mediated Neuropeptides?"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: TRPV1 Protein, Human
Capsaicin
Electric Impedance
Esophagus
Intracellular Space
Pain Measurement
Microscopy, Electron
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2015-11-13
Enrollment: 13
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Changes in mucosal integrity in the distal exposed esophagus during capsaicin infusion compared to control solution.
timeFrame: Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy
Secondary outcomes:
measure: Mucosal integrity in the proximal non-exposed esophagus.
timeFrame: Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy
measure: Induction of dilated intercellular spaces (DIS)
timeFrame: Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy
measure: TRPV1 neuropeptide pathway
timeFrame: Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy
measure: Immunohistochemical expression of TRPV1
timeFrame: Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy
measure: Symptom scores
timeFrame: Testday 1 and 2: during capsaicin and placebo infusion.
measure: TRPV1 neuropeptide pathway
timeFrame: Testday 1 and 2: mucosal biopsies are taken during upper gastrointestinal endoscopy
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center (MUMC+)
name: Jose Conchillo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.