Bitter Tastants and Reflux

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

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.

Study Overview

• Status: Completed
• Conditions: Gastro Esophageal Reflux
• Intervention / Treatment: Dietary supplement: Denatonium Benzoate; Dietary supplement: Water

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bitter; A single intragastric administration of denatonium benzoate (1 µmol/kg)	Dietary supplement: Denatonium Benzoate; A single intragastric administration of denatonium benzoate (1 µmol/kg)
Placebo Comparator: Placebo; A single intragastric administration of placebo (water)	Dietary supplement: Water; A single intragastric administration of water

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2019
• Primary Completion (Actual): May 10, 2019
• Study Completion (Actual): May 10, 2019

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Actual): June 6, 2019
• Last Update Submitted That Met QC Criteria: June 5, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Bitter; TLESRs; Gastric tone
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Aversive Agents; Abuse-Deterrent Formulations; Denatonium
• Other Study ID Numbers: S61251

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No