Effect of Bile Acids on the Secretion of Satiation Peptides in Humans

Study Overview
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Brief Summary
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The purpose of this study is do determine the functional significance of the G protein-coupled receptor TGR5 in the secretion of GI satiation peptides by using natural bile acids and oleanolic acid (triterpenoid compound of plant origin) as TGR5 agonists.

Detailed Description
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TGR5 is expressed in GLP-1-secreting cell lines and L cells from mice; gain- and loss-of-function models suggest a physiological role for TGR5 activation on GLP-1 secretion in rodents. TGR5 signaling showed improved postprandial glucose tolerance in obese mice, associated with marked postprandial GLP-1 release and insulin secretion. In contrast, TGR5-/- mice exhibited reduced glucose tolerance. In animals, TGR5 activation has been shown for natural bile acids (BAs) and triterpenoid compounds of plant origin, such as oleanolic acid (OA), suggesting a role for postprandial BAs in modulating nutrient-induced GLP-1 secretion. We therefore hypothesized that intraduodenal (ID) perfusions of TGR5 agonists (BAs and OA) stimulate the secretion of GLP-1 with respective changes in the glucose metabolism of healthy humans.

Official Title
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Effect of Intraduodenal Perfusion of Bile Acids on the Secretion of Gastrointestinal Satiation Peptides in Healthy Male Volunteers

Conditions
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Echolocation

Intervention / Treatment
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* Other: saline
* Other: bile acid (CDCA, chenodeoxycholic acid)
* Other: oleanolic acid
* Dietary Supplement: oleic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects BMI of 19.0-24.5 Age 18-40 Stable body weight for at least 3 months Exclusion Criteria: Smoking Substance abuse Regular intake of medication Medical of psychiatric illness Gastrointestinal disorders or food allergies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: ID saline<br>ID saline by feeding tube | Other: saline<br>* intraduodenal perfusion<br>|
| Active Comparator: ID saline + CDCA (5 mmol/L)<br>CDCA = chenodeoxycholic acid (primary bile acid) | Other: saline<br>* intraduodenal perfusion<br>Other: bile acid (CDCA, chenodeoxycholic acid)<br>* intraduodenal perfusion<br>* Other names: primary bile acid;|
| Active Comparator: ID + CDCA (15 mmol/L)<br>CDCA = chenodeoxycholic acid (primary bile acid) | Other: saline<br>* intraduodenal perfusion<br>Other: bile acid (CDCA, chenodeoxycholic acid)<br>* intraduodenal perfusion<br>* Other names: primary bile acid;|
| Active Comparator: ID saline + oleanolic acid (1 mmol/L)<br> | Other: saline<br>* intraduodenal perfusion<br>Other: oleanolic acid<br>* intraduodenal perfusion<br>* Other names: triterpenoid compound of plant origin;|
| Active Comparator: ID saline + CDCA (5 mmol/L) + oleic acid<br> | Other: saline<br>* intraduodenal perfusion<br>Other: bile acid (CDCA, chenodeoxycholic acid)<br>* intraduodenal perfusion<br>* Other names: primary bile acid;Dietary Supplement: oleic acid<br>* intraduodenal perfusion<br>* Other names: fatty acid;|
| Placebo Comparator: ID saline + oleic acid (20 mmol/L)<br> | Other: saline<br>* intraduodenal perfusion<br>Dietary Supplement: oleic acid<br>* intraduodenal perfusion<br>* Other names: fatty acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal satiation peptide secretion | Assessment of plasma GLP-1, PYY and CCK release to BA and OA stimulation | 3 hours blood sampling | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum bile acids | Assessment of serum bile acids levels to BA and OA stimulation | 3 hours blood sampling | 
| Appetite perceptions during 3 hours using visual analogue scales | Assessment of the following appetite perceptions markers: feelings of hunger, feelings of prospective food consumption, feelings of fullness and feelings of satiety using validated visual analogue scales | 3 hours | 
| Glucose and insulin secretion | Assessment of plasma glucose and insulin levels to BA and OA stimulation | 3 hours blood sampling | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GI-physiology, CDCA, bile acids, TGR5, satiation peptides