The Effect of Bitter Taste Receptor Agonists on The Gastrointestinal Tract, Hunger and Food Intake

Study Overview
=================
Brief Summary
-----------------
In this study, the investigators aimed at evaluating the role of bitter taste receptors in the gastrointestinal tract (GIT). Intragastric or intraduodenal administration of denatonium benzoate (DB) or quinine hydrochloride were compared with placebo administration for their effects on lingual sensitivity, gastrointestinal motility (both in the fasted and fed state), gut hormone release (motilin, ghrelin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK)) and food intake. Differences between lean and obese subjects will be evaluated.

Official Title
-----------------
The Role of Bitter Taste Receptors Expressed in the Gastrointestinal Tract in Altering Food Intake and Gastrointestinal Motility

Conditions
-----------------
Healthy, Obesity

Intervention / Treatment
-----------------
* Drug: Denatonium benzoate
* Drug: Quinine hydrochloride
* Drug: Tap water


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI>30 kg/m² for the obese volunteers BMI<30 kg/m² for the lean volunteers Subject is capable and willing to give informed consent Female volunteers of child bearing potential must use oral, injected or implanted hormonal methods of contraception Exclusion Criteria: Female volunteer is pregnant or breastfeeding Gastrointestinal diseases, major abdominal surgery Major psychiatric illnesses Volunteers that use drugs affecting the GIT or the central nervous system (CNS) Volunteers that suffer from diabetes mellitus Volunteers suffering from an endocrine disease such as diabetes, Cushing's disease, Addison's disease, hypothalamic tumor… Volunteers that have undergone surgical procedure for weight loss

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Denatonium benzoate intragastric<br>1 µmol/kg bodyweight (10mM) was administered as a bolus into the stomach through a nasogastric feeding tube. | Drug: Denatonium benzoate<br> <br> |
| Active Comparator: Quinine hydrochloride intragastric<br>10 µmol/kg bodyweight (100mM) was administered as a bolus into the stomach through a nasogastric feeding tube. | Drug: Quinine hydrochloride<br> <br> |
| Placebo Comparator: Tap water intragastric<br>An equal amount of tap water was administered as a bolus into the stomach through a nasogastric feeding tube. | Drug: Tap water<br> <br> |
| Active Comparator: Denatonium benzoate intraduodenal<br>1 µmol/kg bodyweight (10mM) was administered as a bolus into the proximal part of the duodenum through a nasogastric feeding tube. | Drug: Denatonium benzoate<br> <br> |
| Active Comparator: Quinine hydrochloride intraduodenal<br>10 µmol/kg bodyweight (100mM) was administered as a bolus into the proximal part of the duodenum through a nasogastric feeding tube. | Drug: Quinine hydrochloride<br> <br> |
| Placebo Comparator: Tap water intraduodenal<br>An equal amount of tap water was administered as a bolus into the proximal part of the duodenum through a nasogastric feeding tube. | Drug: Tap water<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gastrointestinal motility measured by antroduodenal high-resolution manometry |  | 2 hours after administration, continuous measurement with high resolution manometry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut hormone release measured by specific radioactive immunoassays |  | 2 hours after administration, blood sample every 10 min | 
| Change in food intake measured by the caloric content of the meal |  | ad libitum food intake for 1 hour, 40 min after administration | 
| Change in subjective hunger and satiety scores measured by visual analogue scales of 100 mm |  | 2 hours after administration, assessment every 5 min | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy volunteers, Obesity, Bitter