Clinical trial NCT01656057: The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
Official title: The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion
Keywords: Bile acids
Gall bladder emptying
Human
Glucagon like peptide 1
GLP-1
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2012-08-02
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. This action is due to stimulation of the receptor TGR5 by bile acids. Recently scientists have discovered that this receptor in rodents is also expressed on the surface of intestinal L-cells (which normally secrets Glucagon-Like Peptide-1 (GLP-1) in response to nutrient stimulation). The stimulation of this receptor has shown a GLP-1 secretion from the intestinal cells which is interesting since GLP-1 has a central role in maintaining normal glucose tolerance and thus blood sugar. Given the above, bile acids has an important impact on intestinal GLP-1 secretion. Whether these scientific findings can be proven in human beings is uncertain.

The primary hypothesis is that stimulating gall bladder emptying via Cholecystokinin (CCK) in healthy subjects will result in a significant GLP-1 response. We also hypothesize that adding orally Metformin or a sequestrant ("a bile acid binder") will further enhance this GLP-1 response.


Eligibility criteria: Inclusion Criteria:

* HbA1c \< 6,0%
* Not anaemic
* Written informed consent

Exclusion Criteria:

* Liver disease
* Nephropathy
* fasting plasma glucose \> 5,6mM
* Diabetes running in the family (parents or grandparents)
* Any medical treatment
* A former medical history of liver- or bile disease
* any surgical procedure conducted in the abdomen
* Body mass index \< 18,5 kg/m2 or \> 25 kg/m2

Primary outcomes:
measure: GLP-1 response as incremental area under curve (iAUC)
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Secondary outcomes:
measure: Insulin
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Other outcomes:
measure: c-peptide
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: glucagon
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Glucagon-Like Peptide-2
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Peptide YY
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Oxyntomodulin
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Glucose-Dependent Insulinotropic Peptide
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Bile acids
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Gastrin
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: CCK
timeFrame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
measure: Gall bladder emptying assessed ultrasonically
timeFrame: -30, -15, 20, 40, 60, 90, 120, 150, 180
measure: Resting energy expenditure
timeFrame: -10, 50, 210
measure: Estimation of satiety via visual analogue scale
timeFrame: 0, 30, 60, 90, 120, 150, 180, 240
Locations:
city: Copenhagen, Hellerup
country: Denmark
facility: University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division
Study officials:
affiliation: Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital
name: Ulrich Rohde, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rohde U, Sonne DP, Christensen M, Hansen M, Bronden A, Torang S, Rehfeld JF, Holst JJ, Vilsboll T, Knop FK. Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses. J Clin Endocrinol Metab. 2016 May;101(5):2076-83. doi: 10.1210/jc.2016-1133. Epub 2016 Mar 22.