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

Echolocation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01674946
• Other study ID #: EKBB 140/11
• Status: Completed
• Phase: Phase 1
• First received: August 24, 2012
• Last updated: August 24, 2012
• Start date: September 2011
• Est. completion date: May 2012

Study information

• Verified date: August 2012
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Echolocation

Intervention

Other:
• saline
intraduodenal perfusion
• bile acid (CDCA, chenodeoxycholic acid)
intraduodenal perfusion
• oleanolic acid
intraduodenal perfusion

Dietary Supplement:
• oleic acid
intraduodenal perfusion

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Phase 1 Research Unit	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gastrointestinal satiation peptide secretion	Assessment of plasma GLP-1, PYY and CCK release to BA and OA stimulation	3 hours blood sampling	No
Secondary	Serum bile acids	Assessment of serum bile acids levels to BA and OA stimulation	3 hours blood sampling	No
Secondary	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	No
Secondary	Glucose and insulin secretion	Assessment of plasma glucose and insulin levels to BA and OA stimulation	3 hours blood sampling	No