The Effect of Capsaicin and Cinnamaldehyde on Intestinal Permeability

Study Overview
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Brief Summary
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An altered permeability has been proposed to play an important role in the pathogenesis of several gastrointestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease. Nutrients derived from food are able to influence the permeability of the intestine and can therefore also affect gastrointestinal symptoms. In this study, the investigators will investigate the effects of capsaicine and cinnamaldehyde, which can be found in hot peppers and cinnamon, respectively, on gastrointestinal physiology. Objective: To obtain more information about the effects of capsaicin and cinnamaldehyde on the intestine, these substances will be infused directly in the duodenum. Hereafter, the permeability of the intestine, gallbladder motility and the effects on satiety will be assessed. Hypothesis: Duodenal capsaicin and cinnamaldehyde infusion induces changes in the intestinal epithelial barrier function by selectively acting on TRPV1 and TRPA1 receptors and releasing serotonin from enterochromaffin cells as determined by the multi sugar permeability test

Official Title
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The Effect of Capsaicin and Cinnamaldehyde on Intestinal Permeability, Gallbladder Motility and Satiety

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Capsaicin
* Dietary Supplement: Cinnamaldehyde
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Based on medical history and previous examination, no gastrointestinal complaints can be defined. Age between 18 and 65 years. This study will include healthy adult subjects. Subjects over 65 years have an increased risk for comorbidities, therefore, subjects over 65 years will not be included. Furthermore, age has an influence on the homeostasis of the intestinal mucosa [21], which can potentially influence outcome parameters of the study. BMI between 20 and 30 kg/m2 Exclusion Criteria: History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided by the principal investigator. Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator) Dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic), pregnancy, lactation Excessive alcohol consumption (>20 alcoholic consumptions per week) Smoking Blood donation within 3 months before the study period Self-admitted HIV-positive state

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

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 |
| --- | --- |
| Experimental: Capsaicin<br> | Dietary Supplement: Capsaicin<br>* 1.5 mg capsaicin administered intraduodenally<br>|
| Experimental: Cinnamaldehyde<br> | Dietary Supplement: Cinnamaldehyde<br>* 70 mg per intervention administered intraduodenally<br>|
| Placebo Comparator: Placebo<br>Physiological saline | Dietary Supplement: Placebo<br>* Physiological saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of capsaicin and cinnamaldehyde (CA) infusion on intestinal permeability | Measurements performed in plasma | Measured at start and end of infusion (30 min), on each of the 3 test days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of capsaicin and CA infusion on the activation of the TRP receptors as defined by the mucosal concentrations of the neuropeptides SP, CGRP and NKA | Measurements will be performed in mucosal biopsy samples | 1 day | 
| To assess the effect capsaicin and CA on parameters that are known to be associated with satiety, measured by satiety hormones in blood plasma and mucosal tissue (CCK) as well as satiety scoring on a visual analogue scale | Visual analogue scores will be collected from the start of the infusion until 90 minutes thereafter. | 1 day | 
| To assess the effect of capsaicin and CA on serotonergic function in duodenal biopsy specimens by measuring serotonin and its metabolites by HPLC | Measurements will be performed on biopsy specimens | 1 day | 
| To assess the effect of capsaicin and CA on gallbladder motility by ultrasound |  | Measurements will be performed during the testday starting from 08.00 AM to 11.00AM | 
| To assess the effect of capsaicin and CA on the expression of tight junction proteins measured by immunohistochemistry and by quantitative PCR | Measurements will be performed in biopsy specimens of the duodenal mucosa | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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capsaicin, cinnamaldehyde