Bitter Tastants and Reflux

Study Overview
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Brief Summary
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Recently the relationship between intragastric pressure (IGP) and reflux events after a meal was investigated, both in gastro-esophageal reflux disease (GERD) patients and in healthy volunteers. Ingestion of a meal was accompanied by a drop in IGP. However, the magnitude of this drop varied and was inversely correlated with the number of transient lower esophageal sphincter relaxations (TLESRs) and the number of reflux events, both in patients and in healthy volunteers: a smaller meal-induced drop in IGP was associated with a higher rate of reflux events and vice versa. This finding suggests that a smaller meal-induced drop may act as a trigger for reflux. It has been demonstrated that bitter administration leads to a smaller meal-induced drop. Therefore, bitter can be a dietary trigger for TLESRs facilitating the occurrence of symptoms of GERD. To evaluate this hypothesis, the researchers will study the relationship between bitter and the occurrence of TLESRs and reflux events in healthy volunteers. Additionally, it has been demonstrated that administering bitter also influences the concentration of motilin. Therefore, the research team will also measure the concentration of motilin to investigate whether changes in motilin concentrations can influence the number of TLESRs, via a change in gastric tone.

Official Title
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The Relationship Between Acute Administration of a Bitter Compound and Transient Lower Esophageal Sphincter Relaxations and Reflux Events in Healthy Subjects

Conditions
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Gastro Esophageal Reflux

Intervention / Treatment
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* Dietary Supplement: Denatonium Benzoate
* Dietary Supplement: Water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female volunteers Age between 18 and 65 Written informed consent Exclusion Criteria: A history of any upper GI symptoms or GI surgery; Psychological disorders; Concomitant use of other medication or treatments except for oral contraceptives; Use of medication altering esophageal or GI motility; Pregnant or nursing women.

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

Sexes Eligible for Study
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Female

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bitter<br>A single intragastric administration of denatonium benzoate (1 µmol/kg) | Dietary Supplement: Denatonium Benzoate<br>* A single intragastric administration of denatonium benzoate (1 µmol/kg)<br>|
| Placebo Comparator: Placebo<br>A single intragastric administration of placebo (water) | Dietary Supplement: Water<br>* A single intragastric administration of water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in number of TLESRs | Changes in the number of transient lower esophageal sphincter relaxations (TLESRs) between the placebo and bitter condition. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in reflux | The change in the number of reflux events between placebo and bitter condition. | 1 week | 
| Change in motility pattern | The change in the intragastric pressure between placebo and bitter condition. | 1 week | 
| Change in motilin concentration | The change in motilin concentration between placebo and bitter condition. | 1 week | 
| Change in symptoms | Change in the number of volunteers reporting gastrointestinal symptoms between placebo and bitter condition | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bitter, TLESRs, Gastric tone