To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion Clinical Trial
Official title:
The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
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.
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | April 2014 |
| Est. primary completion date | October 2013 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Male |
| Age group | 18 Years to 40 Years |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| Denmark | University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division | Copenhagen, Hellerup |
| Lead Sponsor | Collaborator |
|---|---|
| Filip Krag Knop | University of Copenhagen |
Denmark,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | c-peptide | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | glucagon | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Glucagon-Like Peptide-2 | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Peptide YY | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Oxyntomodulin | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Glucose-Dependent Insulinotropic Peptide | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Bile acids | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Gastrin | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | CCK | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Other | Gall bladder emptying assessed ultrasonically | -30, -15, 20, 40, 60, 90, 120, 150, 180 | No | |
| Other | Resting energy expenditure | -10, 50, 210 | No | |
| Other | Estimation of satiety via visual analogue scale | 0, 30, 60, 90, 120, 150, 180, 240 | No | |
| Primary | GLP-1 response as incremental area under curve (iAUC) | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No | |
| Secondary | Insulin | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 | No |