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

Phase 1

Completed

• Conditions: Echolocation
• Interventions: Other: saline; Other: bile acid (CDCA, chenodeoxycholic acid); Other: oleanolic acid; Dietary Supplement: oleic acid

• Registration Number: NCT01674946
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-09
• Primary Completion: 2011-12
• Study Completion: 2012-05
• Status Verified: 2012-08
• Study First Submitted: 2012-08-24
• Study First Submitted QC: 2012-08-24
• Last Update Submitted: 2012-08-24
• Study First Posted: 2012-08-29
• Last Update Posted: 2012-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ID saline + CDCA (5 mmol/L)	saline	CDCA = chenodeoxycholic acid (primary bile acid)
ID saline	saline	ID saline by feeding tube
ID saline + CDCA (5 mmol/L)	bile acid (CDCA, chenodeoxycholic acid)	CDCA = chenodeoxycholic acid (primary bile acid)
ID + CDCA (15 mmol/L)	saline	CDCA = chenodeoxycholic acid (primary bile acid)
ID + CDCA (15 mmol/L)	bile acid (CDCA, chenodeoxycholic acid)	CDCA = chenodeoxycholic acid (primary bile acid)
ID saline + oleanolic acid (1 mmol/L)	saline	-
ID saline + oleanolic acid (1 mmol/L)	oleanolic acid	-
ID saline + CDCA (5 mmol/L) + oleic acid	saline	-
ID saline + CDCA (5 mmol/L) + oleic acid	bile acid (CDCA, chenodeoxycholic acid)	-
ID saline + CDCA (5 mmol/L) + oleic acid	oleic acid	-
ID saline + oleic acid (20 mmol/L)	saline	-
ID saline + oleic acid (20 mmol/L)	oleic acid	-

Primary Outcome Measures

Name	Time	Method
Gastrointestinal satiation peptide secretion	3 hours blood sampling	Assessment of plasma GLP-1, PYY and CCK release to BA and OA stimulation

Secondary Outcome Measures

Name	Time	Method
Serum bile acids	3 hours blood sampling	Assessment of serum bile acids levels to BA and OA stimulation
Appetite perceptions during 3 hours using visual analogue scales	3 hours	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
Glucose and insulin secretion	3 hours blood sampling	Assessment of plasma glucose and insulin levels to BA and OA stimulation

Trial Locations

Locations (1)

University Hospital Basel, Phase 1 Research Unit; 🇨🇭 Basel, Switzerland