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

University Hospital Basel

Status and phase: Completed; Phase 1

Conditions: Echolocation

Treatments: Other: oleanolic acid; Dietary Supplement: oleic acid; Other: saline; Other: bile acid (CDCA, chenodeoxycholic acid)

Study type: Interventional

Funder types: Other

Identifiers

NCT01674946

EKBB 140/11

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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12 participants in 6 patient groups, including a placebo group

ID saline

Placebo Comparator group

Description:

ID saline by feeding tube

Treatment:

Other: saline

ID saline + CDCA (5 mmol/L)

Active Comparator group

Description:

CDCA = chenodeoxycholic acid (primary bile acid)

Treatment:

Other: bile acid (CDCA, chenodeoxycholic acid)

Other: saline

ID + CDCA (15 mmol/L)

Active Comparator group

Description:

CDCA = chenodeoxycholic acid (primary bile acid)

Treatment:

Other: bile acid (CDCA, chenodeoxycholic acid)

Other: saline

ID saline + oleanolic acid (1 mmol/L)

Active Comparator group

Treatment:

Other: saline

Other: oleanolic acid

ID saline + CDCA (5 mmol/L) + oleic acid

Active Comparator group

Treatment:

Other: bile acid (CDCA, chenodeoxycholic acid)

Dietary Supplement: oleic acid

Other: saline

ID saline + oleic acid (20 mmol/L)

Placebo Comparator group

Treatment:

Dietary Supplement: oleic acid

Other: saline