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

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

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.

Study Overview

• Status: Completed
• Conditions: Echolocation
• Intervention / Treatment: Other: saline; Other: bile acid (CDCA, chenodeoxycholic acid); Other: oleanolic acid; Dietary supplement: oleic acid

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel, Phase 1 Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Christoph Beglinger, MD, University Hospital Basel, Phase 1 Research Unit, Basel Switzerland

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 29, 2012

Study Record Updates

• Last Update Posted (Estimate): August 29, 2012
• Last Update Submitted That Met QC Criteria: August 24, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: bile acids; GI-physiology; CDCA; TGR5; satiation peptides
• Additional Relevant MeSH Terms: Gastrointestinal Agents; Cathartics; Chenodeoxycholic Acid; Bile Acids and Salts
• Other Study ID Numbers: EKBB 140/11